Polyacrylamide hydrogel and employment thereof as endoprosthesis

FIELD: medicine-destination polymers.

SUBSTANCE: invention relates to biologically stable hydrogels to be employed as endoprosthesis consisting essentially of following components: polyacrylamide including acrylamide, crosslinked methylene-bis-acrylamide, wherein acrylamide and methylene-bis-acrylamide are linked at molar ratio from 150:1 to 1000:1. Hydrogel is rinsed with water or physiologic solution so that it contains about 0.5-3.5% polyacrylamide and less than 50 ppm acrylamide and methylene-bis-acrylamide monomers, while modulus of elasticity of hydrogel is approximately 10 to 700 Pa and its complex viscosity about 2 to 90 Pa*sec. Rinsing stage allows removal of nearly all amounts (even trace amounts) of above-indicated monomers resulting in lower toxicity and higher stability of hydrogel. Biologically stable hydrogel is used as injectable prosthesis to fill soft tissues and also to treat or prevent urinary incontinence or anal incontinence. Hydrogel, obtained in a few stages including combining acrylamide and methylene-bis-acrylamide, initiating radical polymerization, and rinsing with apyrogenic water or physiologic solution, is also useful in treatment or prevention of bladder-ureter reflux in mammalians. In all these cases biologically stable hydrogels contain between 0.5 and 25% polyacrylamide.

EFFECT: enlarged resource for manufacturing endoprostheses.

10 cl, 3 dwg, 7 tbl

 

The technical FIELD TO WHICH the INVENTION RELATES.

This invention relates to a new the polyacrylamide hydrogel of cross-linked polyacrylamide. The hydrogel can be obtained by mixing acrylamide and methylene-bis-acrylamide in a ratio such as to give the hydrogel some physical properties. In addition, this invention relates to the application of hydrogel to get the implant for cosmetic surgery and reconstructive surgery, use as an endoprosthesis (filler) soft tissue implant for treating incontinence, the endoprosthesis for the treatment of arthritis, for plastics breast cancer and for the treatment of reflux esophagitis.

PREREQUISITES FOR CREATING INVENTIONS

As implants using natural and synthetic polymers, for example, collagen, soy, glycerin, silicone, polyvinylpyrrolidone and hyaluronic acid. Using substances to be used as implants, usually try to mimic the soft tissue of natural origin, and implies that these substances do not pose a health risk to the patient.

Polyacrylamide gels have also been described. U.S. patent No. 5798096 refers to the biocompatible hydrogel containing from 3.5 to 6.0% cross-linked polyacrylamide. However, in U.S. patent No. 5798096 report that the hydrogel unstable when K is ncentrated crosslinked polyacrylamide 3.5%lower.

Patent of great Britain No. 2114578 refers to polyacrylamide gel medical and biological purposes, containing from 3 to 28% polyacrylamide, and the rest of the hydrogel is saline.

U.S. patent No. 5658329 relates to implantable endoprosthesis comprising a shell filled with polyacrylamide gel, which contains from 2 to 20 wt.% polyacrylamide, and the viscosity of the gel is from 15 to 75 PA·C.

Polyacrylamide product Formacryl®" is an implant soft tissue, consisting of 5% of net polyacrylamide polymer and 95% pyrogen-free water. "Formacryl®" comes in the form of injection equipment for medical or dental appointments for the correction of congenital or acquired defects, such as wrinkles, folds and scars. This endoprosthesis is implanted in the subcutaneous layer with a syringe.

U.S. patent No. 5306404 relates to a method for obtaining plates polyacrylamide gel electrophoresis.

Publication of the international application WO 99/10021 refers to the biocompatible hydrogel for injection containing 0.5-10% polyacrylamide and an antibiotic or an antiseptic.

International application WO 99/10021 aimed at solving suppuration and exclusion gel for use as an endoprosthesis.

SUMMARY of INVENTION

In General, from Britanie refers to biostability the hydrogel, which can be obtained by combining acrylamide and methylene-bis-acrylamide in such amounts that the content of polyacrylamide were about 0.5-25 wt.% (counting on the total weight of the hydrogel); initiating radical polymerization and washing with pyrogen-free water or saline solution. Biostability hydrogel typically has a molecular weight of from 0.01×106up to 20×106. The polymer is resistant to biological decomposition and does not penetrate through biological membranes. Polyacrylamide hydrogel according to this invention is completely biocompatible (according to the standard test ISO: ISO-10993). Polyacrylamide hydrogel has no cytotoxic effect on fibroblasts, it is non-toxic, is not a carcinogen, allergen and mutagen; resistant to enzymatic and microbial decomposition. In addition, the polymer is not soluble in water. This hydrogel is useful as a material for implants and this gel is made specifically to correct a particular defect that requires correction.

One aspect of this invention relates to the biocompatible hydrogel consisting of (i) less than 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water. Specifically, the invention relates to a hydrogel containing (i) m is it than 3.5% (wt./wt.) polyacrylamide, which can be obtained by mixing acrylamide and methylene-bis-acrylamide, initiating radical polymerization; and washing with pyrogen-free water, and the specified combining acrylamide and methylene-bis-acrylamide is carried out at a molar ratio of 150:1 to 1000:1.

The purpose of this invention is to provide a hydrogel for use as an endoprosthesis for injection or implantation, consisting of (i) less than 3.5% (wt./wt.) polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution. This invention relates, furthermore, to a method for producing a hydrogel comprising the stage of combining acrylamide and methylene-bis-acrylamide, initiate radical polymerization and washing pyrogen-free water, so that the content of polyacrylamide was about less than 3.5 wt.%.

Another aim of the invention is injectable or implantable endoprosthesis consisting of (i) less than 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution. In addition, the invention relates to the use of a hydrogel consisting of (i) less than 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution, to get the implant for cosmetic surgery, recon is reconstructive surgery and therapy. It also sets out the method of obtaining injectable or implantable endoprosthesis consisting of the steps of combining acrylamide and methylene-bis-acrylamide (in such a ratio that the content of polyacrylamide was less than 3.5 wt.%), initiate radical polymerization and washing pyrogen-free water or saline solution.

In addition, the invention relates to a method for the treatment of cosmetic or functional defect with an injectable or implantable biocompatible implant consisting of

(a) obtaining a polyacrylamide hydrogel, and the above-mentioned hydrogel contains less than 3.5 wt.% specified polyacrylamide, crosslinked with methylene bis-acrylamide,

(b) injection or implantation of a sufficient number specified hydrogel in the body area affected cosmetic or functional defect.

Hydrogels with a higher content of polyacrylamide is also included in this invention particularly with respect to certain medical indications. Another objective of this invention relates to the application of a hydrogel consisting of (i) more than 9.5 wt.% polyacrylamide (counting on the total weight of the hydrogel) and (ii) pyrogen-free water or saline solution, to obtain implantable endoprosthesis for plastic surgery of the breast.

Another objective of danagoulian refers to the application of the hydrogel, containing 9.5 wt.% polyacrylamide (counting on the total weight of the hydrogel) to obtain the implantable endoprosthesis for contouring.

In this invention apply to the treatment of reflux esophagitis. The use of hydrogel containing more than 6.0 wt.% polyacrylamide (counting on the total weight of the hydrogel), to obtain the implantable endoprosthesis for treatment (reflux) esophagitis is another aim of the invention, as a method of treatment of reflux esophagitis, which consists in the implantation or injection of the endoprosthesis of polyacrylamide hydrogel, in which the hydrogel contains more than 6.0 wt.% polyacrylamide (counting on the total weight of the hydrogel).

To breast plastic surgery also apply to this invention. In addition, this invention relates to method cosmetic changes of the breast or making partial or full plastic breast cancer in women, comprising implantation of polyacrylamide hydrogel; and (i) above, the hydrogel contains more than 9.5 wt.% polyacrylamide (counting on the total weight of the hydrogel) and (ii) pyrogen-free water or saline solution.

Cosmetic surgery of the body (excluding the face) is referred to in this application as contour and is also considered here. In addition, this invention aims at a method of cosmetic change the shape of the mammalian body is found (contour), which consists in the implantation of the prosthesis of polyacrylamide hydrogel; and (i) above, the hydrogel contains more than 9.5 wt.% polyacrylamide (counting on the total weight of the hydrogel) and (ii) pyrogen-free water or saline solution.

Another aspect of this invention relates to hydrogel for use as implant-soft tissue filler of the above hydrogel obtained by combining acrylamide and methylene-bis-acrylamide, initiate radical polymerization and washing pyrogen-free water or saline solution so as to obtain a hydrogel containing less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel.

Another aspect of this invention relates to the application of hydrogel containing less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel) to get the implant for filling soft tissue. Similarly, the invention relates to a method of filling the soft tissues of mammals, consisting in the introduction of the implant, where the implant consists of a hydrogel containing less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel).

Another objective of this invention is to provide a prosthesis to increase the amount of soft tissue, and the above prosthesis is injectable and consists of the aforementioned hydrogel, is received by combining acrylamide and methylene-bis-acrylamide, initiate radical polymerization and washing pyrogen-free water or saline solution so as to obtain a hydrogel containing less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel.

An important aspect of this invention relates to biostability the hydrogel for use in the treatment and prevention of incontinence and vesicoureteral reflux, and the above-mentioned hydrogel is obtained by combining acrylamide and methylene-bis-acrylamide (in such amounts that the content of polyacrylamide ranged from 0.5 to 25 wt.%, counting on the total weight of the hydrogel); initiate radical polymerization and washing pyrogen-free water or saline solution.

Another aspect of this invention relates to the use of biolabeling hydrogel containing from 0.5 to 25 wt.% polyacrylamide (counting on the total weight of the hydrogel), to obtain the endoprosthesis for the treatment and prevention of incontinence and vesicoureteral reflux and to a method of treatment or prevention of urinary incontinence and vesicoureteral reflux, consisting in the introduction of the hydrogel to the mammal, whereby the above-mentioned hydrogel contains from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel.

An important objective of this invention is to provide a prosthesis for increasing resistances and channels, selected from the group consisting of the urethra, rectum or colon and ureter, for the treatment of urinary incontinence, fecal incontinence and vesicoureteral reflux, respectively, and above the prosthesis is injectable and consists of biolabeling hydrogel according to this invention.

One of the purposes of the present invention is to offer a polyacrylamide hydrogel for use as a prosthesis for the addition, enlargement or replacement of cartilage in the intra-articular cavity of the knee joint. Soft material has at least two useful properties, which are that, firstly, the material is biocompatible and biostatician; and, secondly, the material has mechanical elasticity, does not form granules, does not tear and is not falling apart or does not collapse easily under mechanical load. The material can be injected or implanted, and it can be processed in such a way as to distribute the support provided by the material uniformly or in accordance with the needs of the patient. The hydrogel also serves as a lubricant for joints and pre-existing cartilage.

The main purpose of this invention is to provide a hydrogel for use in the treatment or prevention of arthritis, and the above-mentioned hydrogel can receive the e by combining acrylamide and methylene-bis-acrylamide in such quantities, to the content of polyacrylamide were about 0.5-25 wt.%, counting on the total weight of the obtained hydrogel, initiate radical polymerization and washing pyrogen-free water or saline solution.

Another aspect of the invention relates to the application of hydrogel containing about 0.5-25 wt.% polyacrylamide, counting on the total weight of the hydrogel, for the manufacture of the implant for partial withdrawal or prevention of symptoms associated with arthritis.

In addition, the method of treatment or prophylaxis of arthritis, including the introduction of hydrogel to a mammal, whereby the above-mentioned hydrogel contains from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel, is an additional purpose of this invention.

Another aspect of this invention relates to a prosthesis for the treatment of arthritis, where the prosthesis consists of a polyacrylamide hydrogel containing from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel, and above the prosthesis is introduced into the intra-articular cavity of the knee joint. In other words, the prosthesis according to this invention is designed to increase or replacement of cartilage in the intra-articular cavity of the knee joint; and above the prosthesis consists of a polyacrylamide hydrogel containing from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel.

DETAILED ABOUT ISANA INVENTIONS

Hydrogels and their receipt

The success of plastic or reconstructive surgery largely depends on the physical properties of the materials used. These materials must be biocompatible, stable and non-toxic, but they must also have physical characteristics that allow you to mimic the body's tissues, they replace, as in the case of reconstructive surgery, or to simulate tissue near the implant, as in cosmetic surgery.

Substances such as collagen, dissolve in the body for a short time. In the case of materials such as silicone and soy, are faced with serious problems related to patient safety. Currently, there is a need for harmless, biocompatible material that has physical characteristics to simulate soft tissue.

The authors of this invention have unexpectedly found that polyacrylamide hydrogel, containing less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel), is an effective endoprosthesis with useful physical characteristics, and this polyacrylamide gel stable, in contrast to the gel described in U.S. patent No. 5798096. The hydrogel obtained by the method according to this invention, is subjected to cross-linking with methylene-bis-acrylamide, and with Epen stitching is the endoprosthesis made of this hydrogel has a useful physical characteristics. The hydrogel of this invention is a new chemical object, as is shown by his new and useful physical characteristics. These secondary characteristics show that the degree of crosslinking in the hydrogel according to this invention differs from the degree of crosslinking in polyacrylamide hydrogels obtained previously described ways. The degree of crosslinking is a factor in determining the physical properties of the hydrogel.

The authors of this invention have proposed biostability hydrogel obtained by combining acrylamide and methylene-bis-acrylamide (in the amounts necessary to ensure that the content of polyacrylamide ranged from 0.5 to 25 wt.%, counting on the total weight of the hydrogel); initiate radical polymerization and washing pyrogen-free water or saline solution. Molecular weight biolabeling hydrogel is usually from 0.01×106up to 20×106. The polymer is stable, not subject to biological decomposition and does not penetrate through biological membranes. Polyacrylamide hydrogel according to this invention is completely compatible (according to the standard test ISO ISO 10993). Polyacrylamide hydrogel has no cytotoxic effect on fibres the asty person, it is non-toxic, is not a carcinogen, allergen or mutagen; resistant to enzymatic and microbial decomposition. In addition, the polymer is not soluble in water. The main purpose of this invention is to offer hydrogel containing less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, where the above-mentioned hydrogel obtainable by combining acrylamide and methylene-bis-acrylamide, initiate radical polymerization and washing pyrogen-free water or saline solution; and specified the hydrogel is biocompatible, and the mixing is carried out at a molar ratio of reagents from 150:1 to 1000:1.

In other words, one aspect of the invention relates to hydrogel containing (i) less than 3.5 wt.% polyacrylamide (sewn methylene-bis-acrylamide), counting on the total weight of the hydrogel, and (ii) not less than 95% pyrogen-free water or saline solution.

Another aspect of the invention relates to hydrogel for use as injectable or implantable endoprosthesis, and the above-mentioned hydrogel contains (i) less than 3.5 wt.% polyacrylamide (sewn methylene-bis-acrylamide), counting on the total weight of the hydrogel, and (ii) not less than 95% pyrogen-free water or saline solution.

In all variants of implementation of the present invention, in which the hydrogel contains less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel), the hydrogel typically contains, in addition, at least 95% pyrogen-free water or saline solution.

The hydrogel contains less than 3.5 wt.% polyacrylamide, preferably not less than 0.5%, e.g. at least 1%, preferably not less than 1.5% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide, counting on the total weight of the hydrogel.

Hydrogels containing less than 3.5% polyacrylamide, chemically and biologically stable, but can be very (liquid) fluid, so that they can be characterized as compounds having a complex viscosity of at least 2 PA·with, for example, at least 3, 4 or 5 PA·C. acceptable In the embodiment of the present invention, the hydrogel containing less than 3.5% polyacrylamide, characterized by a complex viscosity of from about 2 to 90 Pas·with, for example, 5-80 PA·C, preferably from about 6 to 76 PA·with, for example, from about 6 to 60, from 6 to 40 6 to 20, for example, from 6 to 15 PA·C.

The hydrogel containing less than 3.5% polyacrylamide, has elastic properties, for which the hydrogel can be described as a substance with a modulus of elasticity not less than 10 PA, for example, not less than 20, 25, 30, 31, 32, 33, 34 or 35 PA, such as, for example, not less than 38 PA. Typically, the hydrogel has a modulus of elasticity of from about 10 to 700 PA, for example, from about 35 to 480 PA.

These rheological characteristics partly determine the degree of the crosslinking and the degree of swelling of the hydrogel. The hydrogel containing less than 3.5% polyacrylamide, can be characterized by such a degree of crosslinking of polyacrylamide, which provides effective concentration of cross-linking from about 0.2 to 0.5%, preferably from about 0.25 to 0.4%.

The concentration of cross-linking in turn is partially determined by the molar ratio of acrylamide and methylene-bis-acrylamide. Usually this ratio is between 175:1 to 800:1, for example, from 225:1 to 600:1, preferably from 250:1 to 550:1, most preferably from 250:1 to 500:1. Absolute and relative number of redox agent (TEMED) and initiator also affect the degree of crosslinking. As can be seen in tables 1-4, the authors of the present invention adjust these settings to affect the rheological properties of the hydrogel.

Biocompatible hydrogels according to this invention, containing less than 3.5% polyacrylamide, can in an appropriate case be characterized, at least in part, one or more of the following properties: (i) the concentration of cross-linking from 0.2 to 0.5%; (ii) elastic modulus (G') of from 10 to 700 PA; (iii) a complex viscosity of from 2 to 90 Pas·with; (iv) a dry matter content of less than 3.5%, for example, less than 3,4, for example, less than 3.3, for example, less than 3.2, for example, less 3,1, for example, below 3.0, for example, less than 2,9, for example, less than 2.8, for example, less than the 2.7, and for example, less than 2.6%; (v) the refractive index in the interval of 1.33 and 1.34.

As stated, in all aspects of the present invention, in which the hydrogel comprises less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel, hydrogel, in addition, contains not less than 95% pyrogen-free water or saline solution. In all variants of implementation of the present invention, in which the hydrogel further comprises a saline solution, the hydrogel preferably contains less than 3 wt.% polyacrylamide (counting on the total weight of the hydrogel).

The hydrogel according to this invention contains almost no other substances that contribute to the solids content, in addition to acrylamide, methylene-bis-acrylamide and the residual (if any) initiators. The hydrogel practically does not contain any other polymer. The hydrogel contains at least 75 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water. In an acceptable embodiment of the present invention, the hydrogel contains at least 80 wt.% pyrogen-free water or saline solution, preferably at least 85 wt.%, more preferably at least 90 wt.%, more preferably at least 95 wt.% pyrogen-free water or saline solution.

The hydrogel contains pyrogen-free water or physiological races of the thief. Therefore, mixing of reagents and the casting of the gel can be made in pyrogen-free water or saline solution. The use of saline solution of course is to increase the total mass of solids in the hydrogel, but does not influence significantly on the content of polyacrylamide during the polymerization reaction.

Acceptable saline solution has an osmolarity similar to the osmolarity of the tissue (interstitial) fluid. Acceptable physiological solutions include the group (but not limited to it), selected from 0.25 to 1% aqueous sodium chloride solution, ringer-Locke solution, Earl, Hanks solution, eagle medium, 0.25 to 1% glucose solution, a solution of potassium chloride and calcium chloride. In a preferred embodiment of the present invention saline solution is a 0,8-1% aqueous solution of sodium chloride, for example, 0,8; 0,9 or 1% aqueous solution of sodium chloride.

As mentioned, pyrogen-free water or saline solution used for washing of the gel. The washing process partially removes almost all, even the trace amounts of monomers of acrylamide and N,N'-methylene-bis-acrylamide. These monomers are toxic to the patient, as well as a negative influence on the stability of the hydrogel. Washing should be undertaken so that is concentratie monomers of acrylamide and N,N'-methylene-bis-acrylamide in the hydrogel was less than 50 million -1more preferably less than 40 million-1for example, less than 30 million-1most preferably less than 20 million-1usually less than 10 million-1usually less than 5 million-1. In the method according to this invention stage washing includes the swelling of the product within 50-250 hours, usually within 70-200 PM

Unexpectedly it was found that the hydrogel containing 3.5% polyacrylamide is stable at very low solids contents, in contrast to the disclosures in U.S. patent No. 5798096. Polyacrylamide hydrogels with a solids content of 0.5 wt.% obtained by the authors of the present invention. Preferred options hydrogel according to this invention contain not less than 0.5 wt.%, for example, not less than 1 wt.%, preferably at least 1.5 wt.% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide (counting on the total weight of the hydrogel).

The hydrogel is in an appropriate case, the composition of the chains cross-linked polyacrylamide and pyrogen-free water. Water contained in the hydrogel as part of the composition, loosely (not too tightly) bound polymer chains. When the hydrogel is in the body, some water molecules move into the tissue by osmosis, which results in smoothing the skin surface under the action of the gel. In the embodiment of the invention, in which the hydrogel contains physiologist the ical solution itemelement saline and tissue (interstitial) fluid minimizes immune response.

As mentioned, the physical properties of hydrogel partially influenced by the degree of crosslinking. The degree of crosslinking can be partially controlled by using a molar ratio of crosslinking agent (methylene-bis-acrylamide and acrylamide.

Therefore, another purpose of this invention is a method of obtaining a hydrogel consisting of the steps of combining acrylamide and methylene-bis-acrylamide, initiate radical polymerization and washing pyrogen-free water, so that the content of polyacrylamide was less than 3.5 wt.% (counting on the total weight of the hydrogel). The method preferably is such that gives the hydrogel, which contains at least 0.5 wt.%, for example, not less than 1 wt.%, preferably at least 1.5 wt.% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide (counting on the total weight of the hydrogel).

In a particularly preferred variant of the invention, the hydrogel obtainable by combining acrylamide and methylene-bis-acrylamide in such quantities that the gel contained from 1.6 to 3.5 wt.% polyacrylamide, and in a molar ratio of 150:1 to 1000:1; initiate radical polymerization and washing pyrogen-free water or saline solution.

Combining acrylic is IDA and methylene-bis-acrylamide is preferably carried out at a molar ratio of acrylamide and methylene-bis-acrylamide from 175:1 to 800:1, for example, from 225:1 to 600:1, preferably from 250:1 to 550:1, most preferably from 250:1 to 500:1.

Obtaining a hydrogel of this invention is clearly described in example 1. The hydrogel having the desired physical characteristics obtained by combining acrylamide and methylene-bis-acrylamide in a ratio of about 250:1, for example, 252:1, 254:1, 256:1, 258:1, 260:1, and by combining acrylamide and methylene-bis-acrylamide in a ratio of about 500:1, for example, 498:1, 496:1, 494:1, 492:1, 490:1. The hydrogel according to this invention preferably has a complex viscosity of from about 2 to 90 Pas·with, for example, 5-80 PA·usually from about 6 to 76 PA·with, for example, from about 6 to 60, from 6 to 40 6 to 20, such as 6-15 PA·C. acceptable In the embodiment of the invention stage of the washing cycle includes the swelling of the product stage of initiating radical polymerization up until its complex viscosity is approximately from 6 to 100 PA·C.

In an acceptable embodiment of the present invention, the hydrogel has such a degree of crosslinking that the complex viscosity is not less than 2 PA·with, for example, at least 3, 4 or 5 PA·with, for example, not less than 5.5 PA·with, for example, not less than 6 PA·C, preferably at least 6.2 PA·C.

The modulus of elasticity is another characteristic of Hydra the gel, indicating in part on the degree of crosslinking of the hydrogel according to this invention. Typically, the degree of crosslinking is such that the modulus of elasticity of the hydrogel is at least 10 PA, for example, not less than 25, 30, 31, 32, 33, 34 or 35 PA, for example, not less than 38 PA. The gel can be characterized by the value of the modulus of elasticity of from about 10 to 700 PA, for example, from about 35 to 480 PA.

As stated, in the most preferred embodiment of the invention the hydrogel obtainable by combining acrylamide and methylene-bis-acrylamide in such quantities that the gel contained from 1.6 to 3.5 wt.% polyacrylamide, and when the molar ratio of 150:1 to 1000:1; initiate radical polymerization and washing pyrogen-free water or saline solution. The stage of initiating radical polymerization gives a hydrogel, still contain toxic chemicals and does not yet have useful physical characteristics of the hydrogel according to this invention. Stage washing of the hydrogel includes the swelling of the hydrogel obtained at the stage of radical iniciirovanie, up until its complex viscosity is approximately from 2 to 90 Pas·C.

Or stage of washing may include swelling of the product stage of initiating radical polymerization up until its modulus of elasticity will not be around is about from 10 to 70 PA, for example, from about 35 to 480 PA.

Naturally, the low degree of crosslinking usually results in a higher rate of swelling, consequently, to reduce the dry matter content (percentage acrylamide), and the reduction of modulus of elasticity and viscosity. Thus, along with the degree of crosslinking, the time during which the hydrogel is subjected to washing, significantly affects the physical characteristics of the gel.

Usually stage washing includes the swelling of the product within 80-100 h, for example, 90-95 hours It usually leads to an increase in the mass of the hydrogel approximately 75-150%, typically about 100%.

In addition, the amount of radical polymerization initiator at the initiation stage and the number of coinitiator affect the length of the chain and, consequently, on the physical characteristics of the hydrogel. In a typical example of a hydrogel as coinitiator use N,N,N',N'-tetramethylethylenediamine (TEMED)and ammonium persulfate (APS) is used as an initiator of free-radical polymerization (redox system). To obtain a hydrogel according to this invention requires an adequate amount of initiator and coinitiator. As an example, note that an insufficient number of these reagents will lead to a decrease in chain length and in achiev is Tate will affect the degree of crosslinking and, therefore, the physical characteristics of the hydrogel. Other reaction conditions, such as temperature, also affect the length of the chain.

As mentioned, the degree of crosslinking affects the physical characteristics of the hydrogel. The degree of crosslinking of the hydrogel according to this invention can be determined indirectly, as described above, by using the elastic modulus and/or complex viscosity. Another measure of the degree of crosslinking of the hydrogel is the effective concentration of cross-linking density of the polymer mesh) in it. The hydrogel according to this invention preferably contains from 1.6 to 3.5% (wt./wt.) polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution, preferably, the degree of cross-linking was determined using an effective concentration of cross-linking in the gel, was such that the effective concentration of cross-linking was approximately 0.2%to 0.5%, preferably about 0.25 to 0.4%.

In an acceptable embodiment of the present invention, the hydrogel may contain from 1.6 to 3.25% (wt./wt.) polyacrylamide, for example, from 1.8 to 3.1; from 2.0 to 3.0; from 2.0 to 2.9, preferably from 2.0 to 2.8 (wt./wt.) polyacrylamide.

The use of polyacrylamide hydrogels in medicine

The hydrogels according to this invention are intended for use as endopat the call. The implants according to this invention and in the methods of treatment described herein, the hydrogel can be used in any embodiments of this invention described above.

The implant can be introduced into the human organism by injection, for example, a syringe or catheter, or surgical implantation. In the embodiment of the invention, in which the hydrogel is intended for use as an implantable endoprosthesis, the hydrogel may not necessarily serve substance-filled shell, which together with the filler implanted in the body. Thus, the hydrogel or the endoprosthesis can include a silicone shell that is placed hydrogel.

As stated, the purpose of this invention is a method of treating a cosmetic or functional defect with an injectable biocompatible implant, comprising

(a) receiving and 1.6-3.5 wt.% polyacrylamide hydrogel, and above polyacrylamide sew methylene-bis-acrylamide,

(b) injection of a sufficient quantity of the specified hydrogel in the body area with a cosmetic or functional defect. Hydrogel injection in the specified area, can be obtained by mixing acrylamide and methylene-bis-acrylamide, taken in such quantities that the content of polyacrylamide was 1.6 to 3.5 wt.% and when alarna a ratio of 150:1 to 1000:1, initiating radical polymerization and washing with pyrogen-free water or saline solution. The ratio of acrylamide and methylene-bis-acrylamide is preferably such that the complex viscosity was approximately from 2 to 90 Pas·with, for example, 5-80 PA·C, preferably from about 6 to 76, or such that the modulus of elasticity of approximately from 10 to 700 PA, for example, about 35-480 PA. Stage washing can be performed to such an extent that the complex viscosity was approximately from 6 to 80 PA·to, or to the modulus of elasticity ranged from 10 to 700 PA, for example, 35-480 PA.

The endoprosthesis may consist of any type of hydrogel, as described in this application and may be used or for injection or implantation. Thus, an important aspect of the present invention is the use of hydrogel containing (i) less than 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) not less than 95% pyrogen-free water or saline solution, to get the implant for cosmetic surgery, reconstructive surgery and therapy. In a particularly interesting variants of implementation of the present invention, the endoprosthesis is injectable.

Another purpose of this invention is a hydrogel, as described above, for use in obtaining the endoprosthesis. Concrete is about, the purpose of the invention consists in the application of gel containing (i) from 1.6 to 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution, to get the implant for cosmetic surgery, reconstructive surgery and therapy. Endoprosthesis according to this invention can be injectable or implantable. Cosmetic and reconstructive surgery can correct facial features, for example, by changing the shape or size of the lips, eliminate wrinkles and to treat asymmetry of the face or to change the shape of the nose, as well as perform many corrections persons known to the person skilled in the art. In addition, cosmetic and reconstructive surgery make it possible correction of defects caused by trauma or associated with diseases such as hemiplegia.

The hydrogel, as described above, can be applied to obtain implants. Thus, another purpose of this invention is an injectable implant containing (i) from 1.6 to 3.5 wt.% polyacrylamide, cross-linked methylene-bis-acrylamide, and (ii) pyrogen-free water or saline solution. Injectable implant according to this invention preferably has a complex viscosity of from about 2 to 90 Pas·with, for example, 5-80 PA·C, preferably from about 6 to 76 PA·with, for example, from about 6 to 60, from 6 to 40 6 to 20, for example, from 6 to 15 PA·C. In cases where the implant is introduced by injection, the hydrogel is usually somewhat fluid in nature.

Many diseases are related to the loss of effective activity of the tissue at the functional interface between the two bodies. For example, incontinence of urine due to insufficient activity of the sphincter between the bladder and the urethra. Injection or implantation of the endoprosthesis made of a hydrogel according to this invention, in the submucosa of the proximal urethra leads to narrowing of the urethra that can largely control the disease. Similarly, reflux esophagitis associated with insufficient resistance of the tissue between the esophagus and stomach. By injection or implantation of the endoprosthesis made of a hydrogel according to this invention, along the sphincter between the esophagus and the stomach, it is possible to reduce the contact between the contents of the stomach and esophagus. Thus, in an acceptable variants of implementation of the present invention, the hydrogel is used to produce endoprosthesis for the treatment of urinary incontinence and reflux esophagitis. The endoprosthesis can be used for the treatment of diseases associated with a lack of resistance on the functional boundary between the two bodies is between the parts of one body.

The solids content of the percentage of acrylamide, as determined after the stage of washing and degree of crosslinking adapt to specific endoprosthesis obtained from the hydrogel. In preferred embodiments of this invention, the prosthesis preferably is obtained from a hydrogel containing 1,6-3,25% (wt./wt.) polyacrylamide, for example, 1,8-3,1; 2,0-3,0; 2,0-2,9; preferably between 2.0 and 2.8% (wt./wt.) polyacrylamide. In other words, the preferred degree of crosslinking of the hydrogel designed to correct the shortcomings person, may be such that the complex viscosity of the hydrogel was approximately from 2.0 to 15 PA·with, for example, from about 5.5 to 15 PA·with, for example, from 6 to 12 PA·C. Alternative, the preferred degree of crosslinking of the hydrogel designed to correct the shortcomings person, may be such that the modulus of elasticity ranged from about 10 to 100 PA, for example, from about 35 to 75, more specifically, from 35 to 60 PA, for example, 35-50 PA.

With the help of implants can correct the defects that are the result of trauma, such as a tumor or physical injuries, and birth defects.

In an acceptable embodiment of the present invention the hydrogel, as described above, is used as the filling material to fill or partially is about to fill the container or shell silicone-based for receiving the implantable endoprosthesis. Thus, an additional purpose of this invention is an implantable prosthesis, comprising (i) a hydrogel containing from 1.6 to 3.5% (wt./wt.) polyacrylamide, cross-linked methylene-bis-acrylamide, and pyrogen-free water or saline solution; (ii) a silicone shell that is adapted to accommodate the above-mentioned hydrogel. The hydrogel used for filling or partial filling of the silicone shell can be a hydrogel obtained by combining acrylamide and methylene-bis-acrylamide in such quantities as to obtain a hydrogel containing polyacrylamide from 1.6 to 3.5 wt.%, and in a molar ratio of from 150:1 to 1000:1; initiating radical polymerization and washing with pyrogen-free water or saline solution. In embodiments of this invention, in which the endoprosthesis is implanted, the manufacturer specified the endoprosthesis of hydrogel optionally additionally includes the stage of entry into force of this hydrogel in a silicone shell.

After the hydrogel is placed in a silicone shell, it may preferably be sealed by chemical, mechanical or thermal means or by laser or light. Typically, the external surface of the shell is modified chemically or physically so that it is biocompatible and has to fficient friction, allowing to minimize its movement or slip from position, in which it was placed.

In another embodiment of this invention, the endoprosthesis can include a drug for therapeutic applications.

Polyacrylamide hydrogel as an endoprosthesis (filler) soft tissues

This aspect of the invention the device is indicated for correction of the face, lip augmentation and contouring of the body.

It was assumed that the term "facial (face)" in this aspect of the invention means all that is relevant to all areas of the face, for example, but not exclusively, cheeks, jaw (chin), neck, forehead, under the eyes, head and nose.

It was assumed that the term "contour body" means cosmetic or reconstructive surgery, which carries the increasing volume of soft tissue to correct cosmetic and nekommecheskikh defects of soft tissues of the body, except for the soft tissues of the face, lips, breast and penis.

This aspect of the invention, the term "hydrogel" refers to a polyacrylamide polymer according to this invention, containing less than 3.5% polyacrylamide and at least 95% pyrogen-free water or saline solution, while the term "implant" refers to a hydrogel, which is located in the body.

Polyacrylamide hydrogel can be obtained by polymerization of monomers of acrylamide and N,N-methylene-bis-acrylamide - when radical initiation, followed by washing the polymer pyrogen-free water or saline solution. Washing of the polymer results in the swelling of the gel, which is explained by the absorption of pyrogen-free water or saline solution polymer. Swelling of the hydrogel affects the solids content in the gel, i.e. the number of polymer material is polyacrylamide. The solids content in the hydrogel is influenced, at least in part, on the physical (rheological) properties of the hydrogel and, therefore, on its ability to simulate human tissue, when it is used as an endoprosthesis.

The authors of this invention has been hydrogel having the desired rheological characteristics, so that it could function as an implant soft tissue filler that is completely non-toxic, stable and pressively. The authors of this invention have developed a hydrogel that is especially suited for use as an endoprosthesis for cosmetic and reconstructive surgery of the face, for contouring and for lip augmentation or modification. In this aspect of the present invention, the hydrogel is not prex is assigned for use as an implant for breast augmentation or penile.

The first side of this aspect of the present invention relates to hydrogel for use as an implant soft tissue filler; specified hydrogel obtainable by combining acrylamide and methylene-bis-acrylamide in such quantities as to obtain a hydrogel containing polyacrylamide from 1.6 to 3.5% (wt.), counting on the total weight of the hydrogel; initiate radical polymerization and washing pyrogen-free water or saline solution. Typically, the hydrogel receive the specified mixing acrylamide and methylene-bis-acrylamide when a molar ratio of from 150:1 to 1000:1. The hydrogel thus obtained has the structural formula presented in figure 1, it is sterile, transparent or colorless and the pH is from 6.5 to 9.0, usually from 7.0 to 9.0.

In addition, the hydrogel according to this invention is stable when exposed to oxygen, high pressure, high and low temperatures, enzymes and bacteria.

This aspect of the invention relates to the application of hydrogel containing less than 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel), for the manufacture of the implant for filling soft tissue. If we consider that the hydrogel in this aspect of the invention is intended for use as an endoprosthesis, it must be stable. In addition, if the hydrogel in this aspect and the gaining is intended for use as an endoprosthesis for selected parts of the human body, the hydrogel typically contains at least 0.5 wt.% polyacrylamide (counting on the total weight of the hydrogel, preferably not less than 1.0 wt.% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide (counting on the total weight of the hydrogel). Usually in the hydrogel according to this invention, the solids content may be 5; 1,6; 1,7; 1,8; 1,9; 2,0; 2,1; 2,2; 2,3; 2,4; 2,5; 2,6; 2,7; 2,8; 2,9; 3,0; 3,1; 3,2; 3,3; 3,4 or 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel).

In the preferred embodiment of this aspect of the present invention, the hydrogel contains about 1.9 to 2.9 wt.% polyacrylamide (counting on the total weight of the hydrogel). In addition, the hydrogel typically contains at least 95 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water. In a preferred embodiment, the hydrogel contains at least 96 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water, more preferably not less than 97 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water, for example, 95%; 95,5%; 96%; 96,5%; 97% or 97,5% (wt.) pyrogen-free water or saline solution, preferably pyrogen-free water.

Acceptable saline solution has an osmolarity similar to the osmolarity of the tissue (interstitial) fluid. Acceptable physiological solutions include the group (but not ogran who receive it), selected from 0.25 to 1% aqueous sodium chloride solution, ringer-Locke solution, Earl, Hanks solution, eagle medium, 0.25 to 1% glucose solution, a solution of potassium chloride and calcium chloride. In a preferred embodiment of the present invention saline solution represents approximately 0.8-1.0% aqueous solution of sodium chloride, for example, 0,8; 0,9 or 1% aqueous solution of sodium chloride.

For washing of the gel is used in pyrogen-free water or saline solution. The washing process partially removes almost all, even the trace amounts of monomers of acrylamide and N,N'-methylene-bis-acrylamide. These monomers are toxic to the patient, as well as a negative influence on the stability of the hydrogel. Washing should be undertaken so that the concentration of monomers of acrylamide and N,N'-methylene-bis-acrylamide in the hydrogel was less than 50 million-1more preferably less than 40 million-1for example, less than 30 million-1most preferably less than 20 million-1usually less than 10 million-1most preferably less than 5 million-1.

The solids content of the hydrogel according to this invention is essentially completely determined by the contribution of polyacrylamide and N,N'-methylene-bis-acrylamide and residual amounts of the initiator. The hydrogel contains almost no does the x other polymers.

As mentioned, the hydrogel of this invention is biocompatible, non-toxic, is not an allergen, can not dissolve, chemically inert and resistant to the action of oxygen, high pressure, high and low temperatures, enzymes and bacteria. If the hydrogel is exposed to excessive UV radiation, its physical characteristics change, and it turns into a substance like glue. The advantage is that this substance is also toxic.

With the introduction of the hydrogel implant is surrounded by a thin layer of connective tissue that allows the implant to become a stable part of the connective tissue. Thanks biostability hydrogel and a thin layer of connective tissue, the implant can be easily removed from the body of the patient when he is in the subcutaneous region. This advantage, at least partially, explained by the stability of the hydrogel, which, in turn, at least partly, caused by the process of washing.

Several factors influence the rheological characteristics of the hydrogel, for example, the relative amount of monomer used, the relative amount of initiator, temperature, curing time and other parameters of the polymerization process, and the process of washing. Thus, the polymerization process can give hydrogel is, with many values of viscosity and solids content of less than 3.5 wt.%. This invention is directed to a hydrogel as implant soft tissue filler, and therefore, preferably, if the hydrogel has a viscosity corresponding to the viscosity of the soft tissue it is intended to simulate. The hydrogel of this invention is generally intended for use as an injectable implant for cosmetic or reconstructive surgery of the face, cosmetic or reconstructive surgery of the body (contour) and for lip augmentation or reconstructive plastic surgery of the lips.

The hydrogel according to this aspect of the present invention can be used for injection or implantation into the subcutaneous layer of the epidermis, the preferred injectable hydrogel.

In yet another embodiment of the present invention, the implant is intended for use in cosmetic or reconstructive surgery of the face, and the viscosity of the hydrogel is from about 2 to 100 PA·C, preferably about 5 to 90 Pas·with, for example, from about 10 to 60 PA·C. Most preferably, when the implant designed for use in cosmetic or reconstructive surgery of the face, injected by the injection of a hydrogel.

The viscosity of the hydrogel can vary depending on autoclave and the area of the epidermis of the face, where you want to enter a filler of soft tissues (e.g., chin, unlike cheeks). Accordingly, the hydrogel can be designed for use in cosmetic or reconstructive surgery of the face and to have a complex viscosity of about 2 to 20 PA·C, preferably about 2-18 PA·with, for example, from about 2 to 15, more preferably from 2 to 7 PA·s, most preferably from 3 to 5 PA·C.

In typical embodiments of this invention, the implant may be designed to correct the shortcomings of the contour of the face caused by aging, acne, trauma, surgery, infection or congenital defects. Usually in the correction need such features, as, for example, zygomatic bone, nasolabial folds, eyebrows shifted (fused) in the glabella, the concave shape of the mouth, the chin, the size or shape of the lips, as well as other disadvantages of the soft tissues of the face. The hydrogel restores the contours of the skin, correcting the shortcomings of the contours of the soft tissues of the face, such as wrinkles and folds. The hydrogel can be used to obtain an injectable hydrogel for lip augmentation or repair the many flaws due to congenital defects, trauma or age-related changes.

As stated, this aspect of the invention from OSISA to the use of the hydrogel to obtain endoprosthesis for filling soft tissue, selected from the soft tissues of the face and lips and soft tissues of the body. The hydrogel according to this invention, designed for use in cosmetic and reconstructive surgery of the body (contour), preferably has a complex viscosity of about 5-50 PA·C, preferably about 7-40 PA·s, most preferably about 7-30 PA·C.

In the embodiment of the present invention, in which the hydrogel is used to obtain the endoprosthesis for lip augmentation or reconstruction of the lips, the complex viscosity of the hydrogel is preferably about 2-10 PA·s, more preferably 2-7 PA·s, most preferably about 3-5 PA·C.

Another objective of this aspect of the invention is to provide a prosthesis for increasing soft tissue, and the specified prosthesis is injectable and contains polyacrylamide hydrogel; and the above-mentioned hydrogel obtainable by combining acrylamide and methylene-bis-acrylamide in such amounts that the content of polyacrylamide in the hydrogel was less than 3.5 wt.%, counting on the total weight of the hydrogel; initiate radical polymerization and washing pyrogen-free water or saline solution.

The prosthesis according to this aspect of the invention preferably includes a hydrogel containing at least 0.5 wt.% poly is crylamide (counting on the total weight of the hydrogel), preferably at least 1 wt.% polyacrylamide, more preferably at least 1.5 wt.% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide (counting on the total weight of the hydrogel). Typically, the hydrogel contains about 1.9 to 2.9 wt.% polyacrylamide (counting on the total weight of the hydrogel). The prosthesis consists of a hydrogel, which typically contains at least 95 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water.

Another aspect of this invention relates to a method for filling soft tissue, consisting in the introduction of the implant, where the implant consists of a hydrogel containing less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel. The hydrogel may be the same as described above.

In another embodiment of the invention, the prosthesis comprises cells, such as stem cells. Polyacrylamide provides excellent template and a matrix for cell growth. Although the hydrogel according to this invention allows, as such, to a thin layer of connective tissue from the patient's body was surrounded by the prosthesis, the use of cells in combination with the hydrogel according to this invention upon receipt of the prosthesis allows cell engraftment to the surrounding tissue.

The method according to this aspect of the invention generally consists in the introduction of hydrogel according to this invention by injection of the hydrogel in the subcutaneous is the layer in embodiments of the invention, in which the endoprosthesis is intended for cosmetic or reconstructive surgery of the face and contouring. In the embodiment of the invention, in which the endoprosthesis is designed for lip augmentation or reconstruction of the lips, injection do over the muscle tissue of the lips.

An additional objective of this invention is the use of hydrogel containing (i) more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution, to obtain endoprosthesis for contouring. This method of cosmetic change of the mammalian body (contour), including the implantation of the endoprosthesis of polyacrylamide hydrogel, which contains (i) more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution can be made by injection or implantation of the hydrogel in the soft tissue of the patient.

As mentioned, another option is the implementation of this aspect of the invention consists in the introduction of hydrogel according to this invention in combination with cells, for example stem cells to allow cell engraftment prosthesis.

The method according to this aspect of the invention may include more than one injection in order to cover the desired area or to achieve a desired effect. Gel DL the injection is usually stored in the syringe, suitable for injection such amount that is required for treatment in one session. Depending on the affected area, the amount of gel and, therefore, the volume of the syringe can be changed, for example, a syringe with a volume of 0.25 to 25 ml, for example a syringe selected from the syringe 0.5 ml, 0.7 ml, 1.0 ml, 1.5 ml, 2.0 ml, 2.5 ml, 5.0 ml, 7.5 ml, 10 ml, 12.5 ml, 15 ml, 20 ml, 25 ml Obviously, the prosthesis for use in surgery of the face and lip augmentation will be provided in the form of a set of syringes with different gel volume, which is usually less than the amount offered for prosthesis designed for contouring. For example, a prosthesis for lip augmentation may be provided in volumes of 0.5 ml, 0.7 ml or 1.0 ml, whereas the prosthesis for contouring may be provided in volume of 2.0 ml, 5.0 ml, or 10 ml of These examples are purely illustrative and are not intended to limit the scope of the invention in any way - the prosthesis according to this invention can be offered in any amount necessary for the implementation of the method.

As mentioned, the gel is biocompatible. The method according to this invention does not include an addition to the hydrogel antibiotics, analgesics or protivovospolitelnyh funds.

In a preferred embodiment of the invention, which method consists in the injection of the implant and injection involves using the W syringe with a fine needle, for example, needle 21-29 G. the Right amount of gel injected subcutaneously with back-and-forth swing of the needle. After the implementation of the injection, you may need a simple procedure in order to obtain uniform distribution of the gel. Postoperative swelling can be treated by applying ice to the site of edema, and for the first 2-3 days after the injection, the patient may experience slight pain and may receive redness.

In the embodiment of the present invention, including the injection of the endoprosthesis for lip augmentation or correction of the face, the needle of the syringe is usually extremely thin, for example, 25-29 G. For contouring can be used needle 21-23 G.

Polyacrylamide hydrogel for plastic surgery of the breast

The use of hydrogel containing (i) less than 3.5 wt.% polyacrylamide and at least 95% pyrogen-free water or saline solution, to obtain endoprosthesis for plastic surgery of the breast is the preferred embodiment of this aspect of the present invention. Most preferably, when the endoprosthesis is implanted and further comprises a silicone shell that is placed hydrogel.

In the embodiment of the invention, in which the hydrogel contains less than 3.5 wt.% polyacrylamide, the hydrogel preferably contains at least 1 wt.% polyacrylamide, counting on bwuu weight of the hydrogel, preferably at least 1.5 wt.%, for example, not less than 1.6 wt.% polyacrylamide, counting on the total weight of the hydrogel.

The hydrogels used for plastic surgery of the breast, which contain less than 3.5 wt.% polyacrylamide, preferably are injectable. These injectable implants according to this invention preferably have a complex viscosity of from about 2 to 90 Pas·with, for example, 5-80 PA·C, preferably from about 6 to 76 PA·with, for example, from about 6 to 60, from 6 to 40 6 to 20, for example, from 6 to 15 PA·C.

Another objective of this invention is based on obtaining the authors of this invention hydrogel with high solids content. The use of hydrogel containing (i) more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution, to obtain endoprosthesis for plastic surgery increase or breast reconstruction is an additional aim of the invention. In other words, an additional aim of the invention is a method of changing breast cancer mammals or making partial or full reconstruction of the breast of women, including the implantation of the endoprosthesis of polyacrylamide hydrogel; and specified the hydrogel contains more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (i) not less than 75% pyrogen-free water or saline solution.

In the embodiment of the invention, in which the hydrogel for plastic surgery of the breast contains more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, the hydrogel typically contains less than 25 wt.% polyacrylamide, counting on the total weight of the hydrogel, for example, less than 20%.

Prosthesis for plastic surgery of the breast, in which the hydrogel contains more than 9.5 wt.% polyacrylamide is usually implanted. In the above described embodiments of this invention, the implant may additionally include a silicone shell.

In the case of correction of the consequences of partial or complete amputation of the breast, the implant may be injectable or implantable. When the endoprosthesis is implanted, the implant may contain a hydrogel according to this invention as such. The size and shape of the gel can be detected by obtaining a hydrogel in the form or casting or by giving the hydrogel desired shape and size. Alternatively, before or during implantation of the gel, put it in a silicone shell that is partially used to put the above hydrogel.

In embodiments of this invention, which is preferred implantable endoprosthesis comprising a silicone shell, the hydrogel can be somewhat fluid or what aka any fixed form. In embodiments of this invention, in which the endoprosthesis further includes a silicone shell and the hydrogel has a fixed shape, the size and shape tailored to the needs of the patient, and they can be detected by obtaining the gel form or by casting or by giving the hydrogel desired shape and size. The shell also can be adapted to the size and shape of the hydrogel, in which it is placed. In embodiments of this invention, in which the implantable endoprosthesis does not include additional silicone shell, and the hydrogel is implanted as such, the hydrogel typically has a fixed shape. As mentioned, the shape and size can be adapted to the needs of the patient, and they can be detected by obtaining the gel form or by casting or by giving the hydrogel desired shape and size.

When the cycle is injected for the correction of partial or complete amputation of the breast, the implant preferably is obtained from a hydrogel containing 2.0 to 3.0% polyacrylamide, for example, 2,2-3,0% polyacrylamide and having a complex viscosity of from about 10 to 90 Pas·with, for example, from 20 to 90, 30 to 90, or from 40 to 90 Pas·and a modulus of elasticity of from about 50 to 700 PA, for example, from 75 to 600, from 100 to 500, preferably from about 200 to 500 PA. Typically, the hydrogel has a complex viscosity of at least 10 PA with, for example, not less than 15 PA·s, preferably not less than 20 PA·s, more preferably not less than 30 PA·s, most preferably not less than 40 PA·C.

Polyacrylamide hydrogel for the treatment of urinary and gallbladder-pelvis reflux

Loss of conscious control of the muscles of the sphincter lies at the basis of incontinence of urine and feces. Incontinence, the inability to consciously keep urine in the bladder, is a common disease in the elderly. The muscles of the sphincter of the bladder can be spontaneous, caused by stress, reflex or involuntary. The muscles of the sphincter, caused by stress, leads to involuntary urination, if there is a managed contraction of the muscles of the sphincter of the bladder. When lost control of the sphincter muscle of the bladder, urination can be caused by a slight stress, for example, weak abdominal contractions during the work day, sneezing, coughing, laughing, the release of gases, unexpected events and countless other incentives that may lead to a reduction in the muscles of the sphincter. Incontinence of urine and feces can be caused by age, injury (e.g., paraplegia) or associated with heredity.

Gallbladder-pelvis reflux is the result of reduced MOC technicology resistance, when urine from the bladder is molded back into the kidney. This can lead to the transfer of bacteria from the bladder back into the ureter, renal Cup (calyceal dilation), renal pyramid and the kidneys, and this can lead to infections and recurrent pyelonephritis, and cause physiological damage to the renal parenchyma. This can lead to kidney failure.

Incontinence, fecal incontinence and gallbladder-pelvis reflux can be treated by increasing the resistance of the passage through the urethra, the colon or the rectum (or canalis analis), and the ureter, respectively; known processes obamability.

Attempts to treat urinary incontinence include the use of hydraulic devices (such as described in published application for international patent WO 01/50833 and U.S. patent No. 4969474) and other managed devices, for example, prosthetic sphincter with an inflatable cuff (for example, described in U.S. patent No. 4571749 and the application for international patent WO 01/47433), weight loss, exercise, drug therapy and surgery usually involves lifting the bladder neck or creating increased resistance through the ureter, with surrounding tissue or prosthetic material. For this purpose typically use materials such as collagen, polytetrafluoroethylene (PTFE), silicone and Teflon.

For the treatment of fecal incontinence are managed and regulated device, such as described in published international application WO 01/47431. C gallbladder-pelvis reflux fight by surgery (enlargement of the ureter, usually in childhood) and with antibiotics.

The main purpose of this aspect of the invention is to offer polyacrylamide hydrogel to increase the resistance in the respective channels in the treatment of urinary and gallbladder-pelvis reflux.

In U.S. patent No. 6129761 reported the use of injectable gel and cell compositions for this purpose. Compositions represent the cell suspension, mixed with a biocompatible and virassamy polymer. The polymer provides an environment and a matrix for cell growth and cell engraftment to surrounding tissues. Cell growth coincides with the splitting of the polymer and results in the desired tissue growth. Polymeric materials reported in U.S. patent No. 6129761 consisting of alginates, for example, modified alginates, bacterial polysaccharides, for example, gellan gum, vegetable polysaccharides, for example, karraginanom, hyaluronic acid, copolymers of polyethylene oxide and polypropylenglycol, proteins, such as fibrin, collagen and gelatin, mixtures of polity is enokida and polyacrylic acid, cross-linked chitosan, photochemically crosslinked unsaturated ethylene groups, macromeris, for example, PEG-oligoastrocytoma, polyethylenimine, polylysine, poly(vinylamine) and poly(allylamine). In U.S. patent No. 6129761 not reported on the application of sustainable polyacrylamide hydrogels, but there is evidence of the application capable of cleavage of poly(vinylamine). Biostable polymers, for example, biostability polyacrylamide according to this invention, is unsuitable for the method described in U.S. patent No. 6129761, given the requirements for the polymer according to the invention described in this U.S. patent, to decompose, according to the method in accordance with the invention.

Russian patent No. 2148957 relates to a method for treating cases of cystic-pelvis reflux using a polyacrylamide hydrogel.

Substances for injection, used so far for this purpose are synthetic substances (Teflon, silicone, particles of coal and natural substances (extract connective tissue, fat). Long-term effect for approximately half of the treated patients after a follow-up period of one year was relatively weak with recurrent incontinence. Thus, a need exists for a substance that is biocompatible with the tissue, but at the same time not absorbed and is not excreted by the body (biologically stable). Also what about the, the substance must have the appropriate rheological characteristics to work effectively.

The purpose of this aspect of the present invention is to provide biocompatible and biologically stable polyacrylamide hydrogel to increase the resistance of the channels for the treatment of urinary and gallbladder-pelvis reflux.

It is implied that the term "bistability" means that the substance is not destroyed in any significant degree in the interstitial fluid or tissue of an organism.

One side of this aspect of the invention relates to biostability the hydrogel obtained by combining acrylamide and methylene-bis-acrylamide in such quantities that the polyacrylamide was about 0.5-25 wt.%, counting on the total weight of the hydrogel; a radical iniciirovanie and washing pyrogen-free water or saline solution, for use in the treatment and prevention of urinary and gallbladder-pelvis reflux. Molecular weight biolabeling hydrogel is from 0.01×106up to 20×106. The polymer is resistant to biological decomposition and does not penetrate through biological membranes. Polyacrylamide hydrogel according to this invention is completely biocompatible (standard test ISO: the ISO 10993). Polyacrylamide hydrogel has not cytotoxic on esteem on human fibroblasts it is non-toxic, is not a carcinogen, allergen and mutagen; resistant to enzymatic and microbial decomposition. In addition, the polymer is not soluble in water.

The authors of this invention have found that bistability hydrogel effective as a filler and is suitable for the treatment of urinary and gallbladder-pelvis reflux, taking into account that this gel is biocompatible, does not undergo biological decomposition and does not move from the place of introduction into the channel.

Biostability hydrogel according to this aspect of the invention are usually obtained by combining acrylamide and methylene-bis-acrylamide in a molar ratio of reagents from 150:1 to 1000:1. In the preferred embodiment of this invention, the hydrogel contains less than 15 wt.% polyacrylamide, counting on the total weight of the hydrogel, preferably less than 10%, more preferably less than 7.5%, more preferably less than 5%, most preferably less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel.

Given that the hydrogel according to this aspect of the present invention is intended for use as a permanent implant, it should be stable. In addition, considering that the hydrogel according to this invention is intended for use as an endoprosthesis for selected parts of human body, control the body, the hydrogel typically contains at least 0.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, preferably not less than 1 wt.% polyacrylamide, more preferably at least 1.5 wt.% polyacrylamide, for example, not less than 1.6 wt.% polyacrylamide, counting on the total weight of the hydrogel. Typically, the hydrogel of this invention can have a weight percent solids (dry residue) 1,5; 1,6; 1,7; 1,8; 1,9; 2,0; 2,1; 2,2; 2,3; 2,4; 2,5; 2,6; 2,7; 2,8; 2,9; 3,0; 3,1; 3,2; 3,3; 3,4 or 3.5 wt.% polyacrylamide (counting on the total weight of the hydrogel).

For the treatment of vesicoureteral reflux hydrogel preferably contains less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and approximately 96.5% of pyrogen-free water or saline solution, as, for example, 97.5% of pyrogen-free water or saline solution.

Viscosity biolabeling hydrogel is usually that it can be administered by injection. In a suitable embodiment of the present invention the complex viscosity of the hydrogel is from about 2 to 50 PA·with, for example, about 2-40 PA·C, preferably about 2-30 PA·C, more preferably about 2-20 PA·C.

The prosthesis can have such a viscosity that it can be administered by injection. In one of the embodiments of the present invention, where the hydrogel is injected, the complex viscosity of the hydrogel comp is made from approximately 2 to 30 PA· with, for example, about 2-20 PA·C, preferably about 3-18 PA·s, most preferably about 3-15 PA·with, for example, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 PA·C.

The prosthesis also has elastic properties due, at least partially, high ability of the hydrogel to bind water. This is very important, at least from the point of view of durability and ability to provide resistance to movement through the channels. In a preferred embodiment of the invention, the modulus of elasticity of the hydrogel according to this invention is from 1 to 200 PA, for example, about 2-175 PA, usually about 5-150 PA, for example, 10-100 PA.

Usually the ratio of elastic modulus to the complex viscosity of the prosthesis is 5.8 and 6.4. This invention, therefore, provides a hydrogel with an advantageous combination of characteristics: viscosity, acceptable to the injection of the gel, and elasticity, which increases the resistance (resistance). In combination the preferred embodiments of the invention, the hydrogel has a complex viscosity of less than 25 PA·and the modulus of elasticity of less than 200 PA, preferably, the complex viscosity of less than 15 PA·and a modulus of elasticity of less than 100 PA.

In example 1 and tables 1-4 shows the corresponding conditions to obtain illustrative examples of hydrogels. As you can see, in the preferred kombinirov the nom embodiment of the invention the viscosity of the hydrogel is less than 25 PA· with, and the modulus of elasticity of less than 200 PA; hydrogel can have many meanings of the content of dry residue (wt.%).

In addition, under the preferred combined variant of the invention, the viscosity of the hydrogel less than 25 PA·and a modulus of elasticity less than 200 PA; for example, in the case of a hydrogel with a viscosity of less than 15 PA·and a modulus of elasticity less than 100 PA, the hydrogel can be obtained by combining acrylamide and methylene-bis-acrylamide in a molar ratio of about band 275-1 000, typically 300-800, preferably about 300-500.

The hydrogel according to this invention practically does not contain substances that contribute to the solids content, in addition to acrylamide and N,N'-methylene-bis-acrylamide and residual amounts of the initiator (if they exist). The hydrogel practically does not contain any other polymer. The hydrogel, in addition, contains at least 75 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water. In an acceptable embodiment of the present invention, the hydrogel contains at least 80 wt.% pyrogen-free water or saline solution, preferably at least 85%, more preferably at least 90%, even more preferably at least 95 wt.% pyrogen-free water or saline solution. Acceptable saline solution has an osmolarity similar to osmol is rnost tissue (interstitial) fluid. Acceptable physiological solutions include the group (but not limited to it), selected from 0.25 to 1% aqueous sodium chloride solution, ringer-Locke solution, Earl, Hanks solution, eagle medium, 0.25 to 1% glucose solution, a solution of potassium chloride and calcium chloride. In a preferred embodiment of the present invention saline solution represents approximately 0.8-1% aqueous solution of sodium chloride, for example, 0,8; 0,9 or 1% aqueous solution of sodium chloride.

In a particularly preferred embodiment of this aspect of the invention, the hydrogel contains about 2.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and about 97.5% pyrogen-free water.

Pyrogen-free water or saline solution used for washing of the gel. The washing process partially removes almost all, even the trace amounts of monomers of acrylamide and N,N′-methylene-bis-acrylamide. These monomers are toxic to the patient, as well as a negative influence on the stability of the hydrogel. Washing should be undertaken so that the concentration of monomers of acrylamide and N,N′-methylene-bis-acrylamide in the hydrogel were below 50 million-1, more preferably below 40 million-1for example, below 30 million-1most preferably below 20 million-1usually below 10 million-1usually n is 5 million -1.

Washing can be reasonably implemented within 50-100 h, for example, within 20-225 o'clock In tables 2 and 3 one can see that the process of washing is usually carried out within 50-100 h, in the more typical case for 70-100 hours

In another embodiment of this aspect of the present invention, the prosthesis contains cells, such as stem cells. Polyacrylamide provides an excellent matrix for the synthesis and matrix for cell growth. The use of cells with hydrogel according to this invention for receiving the prosthesis makes it possible cell engraftment to the surrounding tissues of the ureter, urethra or canalis analis. The prosthesis consisting of a hydrogel according to this invention, and the corresponding cells enables greater resistance and greater efficiency in the provision of resistance.

In the preferred embodiment of this aspect of the invention, the hydrogel according to this invention is intended for use in the treatment of incontinence of urine and feces, more preferably incontinence.

Incontinence can be stressful or reflex or involuntary. Typically, the hydrogel according to this invention is suitable for treatment of stress or reflex incontinence.

An additional goal of this aspect of the present invention is to apply the top the hydrogel to obtain the endoprosthesis. Thus, another objective of this invention is the application of the hydrogel, as described above, containing about 0.5-25 wt.% polyacrylamide, counting on the total weight of the hydrogel to obtain endoprosthesis for the treatment and prevention of incontinence and vesicoureteral reflux.

The endoprosthesis in a suitable case is prepared in the form of a suspension for injection. Suspese contains homogenized hydrogel. Usually this Aspasia fill the syringe.

Another objective of this aspect of the present invention relates to a method of treating or preventing incontinence and vesicoureteral reflux, consisting in the introduction mammals specified hydrogel containing about 0.5-25 wt.% polyacrylamide, counting on the total weight of the hydrogel. The hydrogel in any of the above-described embodiments of the invention are suitable for the method according to this invention.

With the introduction of hydrogel thin layer of connective tissue surrounding the implant, which allows the implant to become a permanent part of the connective tissue. Due to the stability of the hydrogel and a thin layer of connective tissue, the implant can be removed from the patient's body. This advantage, at least in part, due to the stability of the hydrogel, which, in turn, at least partially, determined by the process of washing.

Ascollateral affect the rheological characteristics of the hydrogel, for example, the relative amount of monomers used, the relative amount of initiator, temperature and other parameters of the polymerization process and the process of washing. Thus, the polymerization process can obtain hydrogels with multiple values of viscosity. This invention is intended to obtain the endoprosthesis usually for the urethra, rectum or colon (or canalis analis) or to the ureter and, thus, it can be produced in accordance with the requirements of the channel.

An important objective of this invention is to provide a prosthesis for increasing the resistance of the channels selected from the group consisting of the urethra, the rectum or the colon (or canalis analis) and ureter, for the treatment of urinary incontinence, fecal incontinence and vesicoureteral reflux, respectively; where the specified prosthesis is introduced by injection, and includes a hydrogel, as described here.

The method according to this aspect of the invention preferably includes the introduction of hydrogel by injection of the hydrogel to the corresponding channel. In the treatment of urinary incontinence, usually inject hydrogel into the urethra, specifically for submucosal membrane of the urethra. Injections are made in the outer surface with this in place is part of the channel, in the direction of the submucosal shell.

The authors of this invention have found that it is usually acceptable is the number of 2-5 ml of the hydrogel, in order to provide adequate resistance in the urethra by filling this channel. Usually injected 3 ml of the hydrogel, and preferably 2-5 ml distribute, by placing the gel in more than one transverse position along one position in the longitudinal direction of the urethra. In a particularly appropriate embodiment of this invention three or more servings of gel is placed (make 3 or more depot) along one position in the longitudinal direction of the urethra. The authors of this invention have found that particularly suitable are the portions of the gel (depot) at a distance of 0.5 cm from the bladder neck.

The authors of this invention have shown that injection into the submucosal in position 10, 2 and 6-clockwise in the cross-section of the urethra are particularly suitable for the treatment of urinary incontinence.

Depot usually done with a syringe or using Cytoscape or catheter. These injections are suitable needle 21-27 G.

For the treatment of fecal incontinence injections hydrogel usually do in the colon or rectum (canalis analis), specifically under submucosal membrane of the colon or rectum. When mlami injection 2-6 ml of hydrogel. Preferably, when the hydrogel is distributed in more than one transverse position along one position in the longitudinal direction of the colon or rectum. In a particularly appropriate embodiment of the present invention have three or more depots along one position in the longitudinal direction of the colon or rectum, preferably in positions 10, 2 and 6-clockwise cross-section of the colon or rectum.

For the treatment of vesicoureteral reflux requires injection into the submucosal ureter. Acceptable injection 2-5 ml Hydrogel distribute preferably more than one transverse position for one position in the longitudinal direction of the ureter. In a particularly suitable embodiment of the present invention make 3 or more depots along one position in the longitudinal direction of the ureter, preferably in positions 10, 2 and 6-clockwise cross-section of the ureter.

In another embodiment of the present invention the method includes the use of a prosthesis containing cells, such as stem cells. Polyacrylamide provides excellent template and a matrix for cell growth. The use of cells in combination with the hydrogel according to this invention for receiving the prosthesis makes it possible cell engraftment to others is Canam ureter, urethra or canalis analis. The method comprising the hydrogel of this invention and the corresponding cells, enables greater resistance and greater efficiency in the provision of resistance.

Polyacrylamide hydrogel for treatment of arthritis

Arthritis is a degenerative condition which, affecting the joints, bearing the body weight, for example, hip and knee joints, causes pain and leads to limited mobility. Arthritis can affect all the joints. Degeneration of articular and meniscal cartilage can cause damage to the surfaces, which separates the cartilage, and, respectively, to cause pain. Aging is the primary cause of degeneration of the cartilage. Degeneration may be caused, for example, congenital predisposition or injury, for example, repeated articulation of the joint.

Arthritis treated traditionally physiotherapeutic methods, and also use more radical methods of treatment, for example, surgical orthopedics and the introduction of artificial components of the joints. With some success used nonsteroidal anti-inflammatory agents, but these agents may be counterproductive, preventing the synthesis of proteoglycan to collagen in the joints, and also have unwanted side effects. Cortisone injections are also over time sublet articular cartilage.

Soft elastic materials, which are used for joint replacement, designed to take the burden of joint and evenly distributed the load. In U.S. patent No. 4344193 described prosthesis made of silicone rubber. The only problem with these prostheses is the fixation of the prosthesis in place, and various systems have been developed for the fixation of the prosthesis (see U.S. patent No. 5171322, No. 4502161 and No. 4919667).

Other prostheses, for example, described in U.S. patent No. 5344459 are inflatable. The prosthesis knee joint Macintosh is a rigid prosthesis and causes pain when used.

The publication of the application for international patent WO 00/78356 described injectable composition for stimulating growth of bone and/or joint, containing hyaluronic acid, cross-linked with sulfated polysaccharides.

The publication of the application for international patent WO 00/24129 reported a prosthetic device for joints of the hands and soles of the feet, consisting of a biocompatible material, for example, a mixture of biocompatible resins and plastics. Specific materials are mentioned, include polymetylmetacrylate polymer. The prosthesis is implanted in the joint. The publication of the application for international patent WO 00/59411 described a knee prosthesis that is implanted surgically in which the prosthesis is to distribute the load made of material the and, containing curable by heating the polymer or thermoplastic polymer. The hyaluronates and hyaluronic acid is used for prostheses and is administered by injection into the intra-articular cavity of the knee for long-term relief of pain and improved knee function. The prosthesis has sufficient viscosity and elasticity, but he has a tendency to deviation from the desired position, is biodegradable, and in this case, face problems resorption (resorption).

There is a need for additional materials for use as artificial cartilage, for example, in the joints, bearing the body weight. The purpose of this invention is the material and prosthesis for use in the treatment of arthritis and for additions or replacement of cartilage.

Polyacrylamide hydrogel resistant to biological breakdown and does not penetrate through biological membranes. Polyacrylamide hydrogel according to this invention is completely biocompatible (according to the standard test ISO: the ISO 10993). Polyacrylamide hydrogel has no cytotoxic effect on fibroblasts, non-toxic, is not a carcinogen, allergen and mutagen; resistant to enzymatic and microbial decomposition. In addition, the polymer is not soluble in water. What is important for the present from which retene, the polymer possesses elasticity under mechanical load.

The hydrogel according to this aspect of the invention is intended for use for the treatment and prevention of arthritis, the hydrogel is obtained by combining acrylamide and methylene-bis-acrylamide; initiate radical polymerization and washing pyrogen-free water or saline solution, and connect the same quantities of reagents and washing is carried out so that the content of polyacrylamide was approximately 0.5 to 25 wt.%, counting on the total weight of the hydrogel. The authors of this invention have shown that the obtained hydrogel is as biostatician and biocompatible, and is not absorbed into the body. In addition, the authors of this invention have demonstrated that the hydrogel has an elastic mechanical load.

Typically, the hydrogel according to this aspect of the invention is obtained by combining acrylamide and methylene-bis-acrylamide in a molar ratio of from 150:1 to 1000:1. Conditions for obtaining hydrogel can be changed in accordance with, for example, type of joint, in which the hydrogel is introduced. The desired rheological characteristics, such as elasticity and viscosity can be regulated, at least partially, the solids content of the hydrogel. In suitable embodiments of this invention, the guide is ogel contains less than 15 wt.% polyacrylamide, counting on the total weight of the hydrogel, preferably less than 10%, more preferably less than 7.5%, more preferably less than 5%, most preferably less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel.

Taking into account that the hydrogel according to this invention is intended for use as an endoprosthesis, it must be stable. Typically, for example, for reasons of increased stability, the hydrogel contains at least 1 wt.% polyacrylamide (counting on the total weight of the hydrogel, preferably at least 1.5 wt.% polyacrylamide, for example, 1.6 wt.% polyacrylamide (counting on the total weight of the hydrogel). In suitable embodiments of this invention, the solids content of the hydrogel according to this invention is 1,5; 1,6; 1,7; 1,8; 1,9; 2,0; 2,1; 2,2; 2,3; 2,4; 2,5; 2,6; 2,7; 2,8; 2,9; 3,0; 3,1; 3,2; 3,3 and 3.4 wt.% polyacrylamide (counting on the total weight of the hydrogel).

Mixing involves mixing the component parts of reagents acrylamide and methylene-bis-acrylamide, usually degassed and usually in such a way as to minimize contact with the operator. Part of the reagents can be pre-mixed (this is optional) and receive inert mixture. Inert mixture is a mixture in which between its constituent reagents are not going chemical reactions. Mixing means the Association of South Africa is amide, methylene-bis-acrylamide and the component, which is the radical initiator. In an acceptable embodiment of the present invention previously prepared mixture of acrylamide, methylene-bis-acrylamide (cross-linking agent) and TEMED is mixed with a solution of the initiator ammonium persulfate (AMPS). However, these components can be mixed individually or in the form of many other pre-prepared mixtures.

Acrylamide and methylene-bis-acrylamide are mixed in a molar ratio from about 100:1 to 1000:1, usually from about 100:1 to 900:1, preferably from about 175:1 to 800:1, more preferably from about 200:1 to 600:1, most preferably from about 250:1 to 500:1. As shown in Tables 2 and 3, it is possible to regulate the process and to obtain hydrogels with different solids contents and the desired rheological characteristics. The hydrogel with the desired rheological characteristics is obtained by mixing acrylamide and methylene-bis-acrylamide in a ratio of about 250:1, 260:1, 270:1, 280:1, 290:1, 300:1, about 310:1, 320:1, 330:1, about 340:1, 350:1, about 360:1, 370:1, 380:1, about 390:1, 400:1, 410:1 about 420:1, about 430:1, 440:1, 450:1, 460:1, about 470:1, 480:1, about 490:1 and about 500:1.

As can be seen in tables 2 and 3, the relative amount of monomer (acrylamide and stands the bis-acrylamide) in relation to the TEMED remains pretty constant from recipe to recipe. Thus, in a preferred embodiment of the method according to this invention, the ratio of monomers and TEMED is relatively constant from batch to batch, and it is not used to regulate the rheological characteristics of the polymer. In the embodiment of the invention, in which the polymer is polyacrylamide, the ratio of the monomers of acrylamide and methylene-bis-acrylamide TEMED to be approximately 100:1 to 700:1, for example, from 200:1 to 600:1, typically from 200:1 to 500:1, preferably from 200:1 to 400:1, most preferably from 200:1 to 350:1.

Similarly, the relative amount of monomer (acrylamide and methylene-bis-acrylamide) in relation to the number of initiator remains fairly constant from recipe to recipe. Thus, in a preferred embodiment of the method according to this invention, the ratio of the monomers and the initiator is relatively constant from batch to batch, and it is not used to regulate the rheological characteristics of the polymer. In the embodiment of the invention, in which the polymer is polyacrylamide, the ratio of the monomers of acrylamide and methylene-bis-acrylamide to initiator is from about 100:1 to 700:1, for example, from 200:1 to 600:1, typically from 200:1 to 500:1, preferably from 200:1 to 400:1, most preferably from 200:1 to 350:1.

The viscosity of hydrog the La, respectively, shall be such as so it can be injected. In a typical embodiment of the invention the complex viscosity of the hydrogel is from about 2.0 to 20 PA·with, for example, from about 3 to 18 PA·C, preferably from about 3 to 15 PA·s, most preferably from about 2 to 13 PA·C.

The hydrogel according to this invention practically does not contain substances that contribute to the solids content, in addition to acrylamide, methylene-bis-acrylamide and residual amounts of the initiator (if they exist). The hydrogel practically does not contain any other polymer. The hydrogel, in addition, contains at least 75 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water. In an acceptable embodiment of the present invention, the hydrogel contains at least 80 wt.% pyrogen-free water or saline solution, preferably at least 85%, more preferably at least 90%, even more preferably at least 95 wt.% pyrogen-free water or saline solution.

Acceptable saline solution has an osmolarity similar to the osmolarity of the interstitial fluid. Acceptable physiological solutions include the group (but not limited to it), selected from 0.25 to 1% aqueous sodium chloride solution, ringer-Locke solution, Earl, Hanks solution, eagle medium, 0.25 to 1% of the races is the thief of glucose, solution of potassium chloride and calcium chloride. In a preferred embodiment of the present invention saline solution is a 0,8-1% aqueous solution of sodium chloride, for example, 0,8; 0,9 or 1% aqueous solution of sodium chloride, most preferably of 0.9% aqueous sodium chloride solution.

To a person skilled in the art it is clear that in the embodiment of the invention, where a saline solution is used for both receive and washing of the gel, the solids content of the gel is higher than the contribution of polyacrylamide, but usually not more than an additional 1%.

In a particularly suitable embodiment of the invention, the hydrogel contains about 2.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and approximately 97.5% pyrogen-free water.

Pyrogen-free water or saline solution used for washing of the gel. The washing process partially removes almost all (even trace) amounts of monomers of acrylamide and N,N'-methylene-bis-acrylamide. These monomers are toxic to the patient, as well as a negative influence on the stability of the hydrogel. Washing should be undertaken so that the concentration of monomers of acrylamide and N,N'-methylene-bis-acrylamide in the hydrogel was less than 50 million-1more preferably less than 40 million-1on the example, less than 30 million-1most preferably less than 20 million-1usually less than 10 million-1especially preferably less than 5 million-1.

In another embodiment of the invention, the hydrogel has a more solid texture, which allows to implant it in the joint cavity. In such embodiments of the invention, where the gel has a firm texture, the surface of the gel can be modified in such a way as to reduce slippage of the gel from places where it is implanted. Surface modification can be chemical or physical in nature. The obtained hydrogels with such solids, which are similar to solids and are more useful for implantation than for injection, and their surface is easy to modify.

In the embodiment of the present invention, where the hydrogel is implanted, the viscosity of the solid sample is obviously very high. In the embodiment of the present invention, where the hydrogel is implanted, the complex viscosity of the hydrogel is from about 20 to 1500 PA·usually from 20 to 1000 PA·C.

In the embodiment, this aspect of the present invention, where the hydrogel is implanted and, in addition, its surface is modified, in the case of modification of the surface of the gel chemical obrabotka is expected that chemical treatment will affect less than 1% by weight of the hydrogel, counting on the total weight of the hydrogel. Chemical treatment may include the agent covering the surface, or the agent, the action of which is to chemically modify polyacrylamide on the surface of the hydrogel.

The hydrogel according to this aspect of the present invention is used for receiving the implant, which is inserted into the intra-articular cavity of the knee joint. The gel is intended for use as a prosthesis for the treatment of arthritis. The prosthesis according to this invention consists of polyacrylamide hydrogel containing from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel, it is introduced into the intra-articular cavity of a joint.

The prosthesis may be composed of any of a variant embodiment of the hydrogel, as described above. Accordingly, the prosthesis is designed to increase or replacement of cartilage in the intra-articular cavity of the knee joint, with the specified prosthesis consists of a polyacrylamide hydrogel containing from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel. The prosthesis of the hydrogel according to this invention typically further contains at least 75 wt.% pyrogen-free water or saline solution, preferably pyrogen-free water. It can be administered by implantation or injection into the intra-articular cavity of the knee joint. Prefer inim is injectable prosthesis.

The prosthesis can have a viscosity, which makes possible its introduction by injection. In one of the embodiments of the invention, where the hydrogel is injectable, the complex viscosity of the hydrogel is from about 2.0 to 25 PA·with, for example, from about 3 to 20 PA·C, preferably from about 3 to 18 PA·s, most preferably from about 3 to 15 PA·with, for example, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 PA·C.

The elasticity of the hydrogel and the prosthesis is important, especially for such a variant embodiment of the invention, where the hydrogel is injected into the joint, supporting the body weight. In a preferred embodiment, the modulus of elasticity of the hydrogel according to this invention is approximately from 1 to 200 PA, for example, from about 2 to 175 PA, usually from about 5 to 150 PA, for example, 10-100 PA.

Usually the ratio of the modulus of elasticity of the prosthesis to its complex viscosity is 5.8 and 6.4. This invention, therefore, provides a hydrogel with an advantageous combination of characteristics: viscosity, suitable for ineterest gel, and elasticity, providing the ability to carry a load of body weight. In combination the preferred embodiments of the invention, the hydrogel has a complex viscosity of less than 25 PA·and the modulus of elasticity of less than 200 PA, preferably, the complex viscosity of less than 15 PA·and the elastic module is tis less than 100 PA.

In example 1 and tables 1, 2 and 3 presents the appropriate conditions to obtain illustrative examples of hydrogels. As you can see, in the preferred combined embodiment of the invention, where the viscosity of the hydrogel is less than 25 PA·and the modulus of elasticity of less than 200 PA, for example, the complex viscosity is less than 15 PA·and a modulus of elasticity of less than 100 PA, the hydrogel can have many meanings of the content of dry residue (wt.%).

In addition, in the preferred combined embodiment of the invention with a viscosity of hydrogel less than 25 PA·and a modulus of elasticity less than 100 PA, for example, in the case of a hydrogel with a viscosity of less than 15 PA·and a modulus of elasticity less than 200 PA; hydrogel is obtained by combining acrylamide and methylene-bis-acrylamide in a molar ratio of from about 275 to 1000, typically 300-800, preferably in a ratio of about 300-500.

The hydrogel according to this invention has elasticity under mechanical load, and also provides the grease inside the joint. This simulates a combination of natural cartilage and synovial fluid in the joint. Synovial fluid is produced by the synovial membrane and is formed at the interface of the synovial membrane and articular cartilage. The function of the synovial fluid is the power of cartilage lubrication, the bearing load pogloshenie shocks (see Gomez and Thurston, Biorheology 30, 409-427 (1933)). Synovial fluid is a solution of a very complex polymer compound having a skeleton of the linear hyaluronic acid and protein branches; it has a modulus of elasticity G', equal to 60 PA and a complex viscosity of about 1-10 PA·C. the variations of a hydrogel according to this invention have the same modulus of elasticity and a close value of viscosity.

Synovial fluid, as a fluid, has a very long relaxation time (about 100 seconds). The relaxation time is defined as the time required to load decreased to 37% of its initial value in the experiment on the relaxation of the load. This long relaxation time means that for fast movements (when the load is attached quickly), synovial fluid reacts as a very elastic material, whereas at low speed application loads it behaves as a lubricating oil. The hydrogel formulations with low viscosity in this invention is similar to the fluid, for example, when they are homogenized, and like liquids have very long relaxation time and properties similar to the properties of the synovial fluid. This invention, therefore, provides an excellent alternative to known technologies to replace synovial the Noah fluid, for example, by injection of isotonic saline (NaCl) water, which are held only within 1-3 days, or by injection of solutions of hyaluronic acid, in this case face the problems of resorption.

As mentioned, in those embodiments of the invention, in which the hydrogel is a recipe with low viscosity, using hydrogel trying to mimic, at least in part, the characteristics of synovial fluid. In those embodiments of the invention, in which the hydrogel is a recipe with a higher viscosity, for example, with a viscosity higher than 10 PA·with, for example, above 15 PA·C, the hydrogel mimics largely merged characteristics of synovial fluid and cartilage that is reflected in the fact that the hydrogels are more elastic materials with infinitely large relaxation times.

From the point of view of elasticity with respect to mechanical load, the hydrogel according to this invention showed a fully elastic behavior of the material. In addition, the elastic properties of the hydrogel allow it to return to its original position after removal of the load in the experiments investigating the creep.

The prosthesis can be entered in a variety of intra-articular cavities, where the specified joint or cartilage that is present in the specified joint, may require the enhanced lubrication, increased ability to withstand body weight or enhanced protection of the opposing bones in the joint, as for example in the group (but not limited to this group), including the knee, hip, elbow, metacarpophalangeal and interphalangeal joints of the hands and feet (accepted comments on other important joints.

With the introduction of the prosthesis to the patient is very important for proper posture and placement of the hydrogel. To aid in placement of the gel is very useful visualization of the localization of the prosthesis to the individual performing the procedure. It may be useful, for example, in the embodiment of the invention, where the prosthesis is administered by injection to visualize the prosthesis to determine its position and the quantity required. Visualization of the hydrogel at the time of introduction may contribute radioactive label hydrogel. Thus, in one interesting embodiment of the present invention, the hydrogel mark radioactive isotope.

As stated, the surface of the hydrogel may help to hold the prosthesis in place inside the cavity of the joint. However, in the form of an injectable hydrogel prosthesis can keep the bone tissue which defines the boundaries of the cavity, into which is injected a gel.

As was also indicated, one aspect of this invention relates to the use of hydroge what I containing from about 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel, for receiving the implant for partial withdrawal or prevention of symptoms associated with arthritis. Accordingly, the method according to this invention can be characterized as a method of treatment or prophylaxis of arthritis, consisting in the introduction of the hydrogel to the mammal, whereby the above-mentioned hydrogel contains from 0.5 to 25 wt.% polyacrylamide, counting on the total weight of the hydrogel. The method includes applying a hydrogel as defined above, and the use of the prosthesis as defined above.

The method may include the first series, or the course of treatment by injection or implantation with subsequent analysis, evaluation or opinion about the level of assistance provided by the prosthesis, and the subsequent additional series or courses of treatment, if required. In the embodiment of the invention, in which you primarily increased the ability of the joint to transfer the load of body weight, firmness or support, which ensures that the prosthesis may eventually decrease. However, one advantage of the method according to this invention is that injectable prosthesis can be entered as an addition to an existing denture. The procedure can be repeated as often as required by the patient to relieve the pain associated with it. Similarly,in the case when the prosthesis is introduced primarily in order to enhance the lubrication of the joint and the ability of the prosthesis to lubricate the joint decreases over time; the method according to this invention, for example, a simple injection can be repeated when required.

Polyacrylamide hydrogel for phalloplasty

Another purpose of this invention is the use of hydrogel containing (i) less than 1.6 wt.% polyacrylamide, counting on the total weight of the hydrogel, for receiving the implant to enlarge penis. This method of increasing your penis size, consisting in the introduction of polyacrylamide hydrogel, where the hydrogel contains less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, usually carried out by injection. Introduction by injections into the cavernous tissue.

The hydrogel is typically further comprises at least 95% pyrogen-free water or saline solution. Thus, a particularly interesting variant implementation of the invention consists in the application of the hydrogel, containing (i) less than 1.6 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) not less than 95% pyrogen-free water or saline solution to obtain your surgery for penis enlargement, preferably injectable implant. Injectable implants for penis enlargement are usually comp is exnow viscosity of less than 20 PA· with, for example, less than 18 PA·s, preferably less than 15 PA·C. in Addition, these implants typically have a modulus of less than 150 PA, usually less than 100 PA.

Another purpose of this invention is the use of hydrogel containing (i) more than 9.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution, to obtain implantable endoprosthesis for penis enlargement. This method of increasing your penis size, consisting in the implantation of the prosthesis of polyacrylamide hydrogel, where the hydrogel contains (i) more than 9.5 wt.% polyacrylamide, and (ii) pyrogen-free water or saline solution, can be carried out by implantation or injection of the endoprosthesis.

The hydrogel prosthesis to enlarge the penis, contains not less than 9.5 wt.% polyacrylamide has a complex viscosity of at least 10 PA·with, for example, not less than 15 PA·s, preferably not less than 20 PA·s, more preferably not less than 30 PA·s, most preferably not less than 40 PA·C. the Gels of high viscosity suitable for implantation and have a dense consistency from semi-soft to semi-rigid consistent with this goal.

Polyacrylamide hydrogel for the treatment of esophagitis

Another objective of this invention consists in the application of the hydrogel, containing (i) bol is 6 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution, to obtain endoprosthesis for treatment (reflux) of esophagitis. In an acceptable embodiment of the invention, the hydrogel contains more than 7, 8 or 9% polyacrylamide. This method of treatment (reflux) esophagitis, consisting in implantation or injection of the endoprosthesis of polyacrylamide hydrogel, where the hydrogel contains more than 6 wt.% polyacrylamide, counting on the total weight of the hydrogel, can be carried out by implantation or injection of the endoprosthesis, usually by injection or implantation into the submucosal tissue layer.

Another objective of this invention consists in the application of the hydrogel, containing (i) less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and (ii) pyrogen-free water or saline solution, to obtain endoprosthesis for treatment (reflux) of esophagitis. This method of treatment (reflux) of esophagitis can be performed by implantation or injection of the hydrogel, where the hydrogel contains less than 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel. In the treatment (reflux) esophagitis using hydrogel containing (i) less than 3.5 wt.% polyacrylamide, usually hydrogel further comprises at least 95% pyrogen-free water or saline solution, and the treatment is usually carried out by injection. In these embodiments, the wasp is estline of this invention, the degree of crosslinking can be so, that viscosity is not less than 6 PA·with, for example, from 6 to 90 Pas·with, for example, from 10 to 80 PA·C, preferably from 20 to 80 PA·C. the Degree of crosslinking of the hydrogel used to obtain the endoprosthesis for treatment (reflux) of esophagitis may be such that the modulus of elasticity of the hydrogel to be approximately 50 to 700 PA, for example, from 75 to 600 PA, for example, from 100 to 500 PA, preferably from about 200 to 500 PA. Typically, the hydrogel has a complex viscosity of at least 20 PA·s, more preferably not less than 30 PA·s, most preferably not less than 40 PA·C.

The invention is hereinafter disclosed with the aid of examples which are not intended to limit the invention in any way.

EXAMPLES

Example 1

Obtaining hydrogel

The gel is a polyacrylamide gel, obtained by polymerization of monomers of acrylamide and N,N'-methylene-bis-acrylamide. The final product may have a different viscosity.

The hydrogel has the empirical formula [(C3H5NO]x[C7H10N2O2]yand the structural formula shown in figure 1.

The hydrogel typically contains approximately 95% water. As shown, the concentration of monomers of acrylamide and N,N'-methylene-bis-acrylamide is less than 10 million-1often less than 5 million-1and corresponds to stable the tee of the final product.

The final product must comply with the requirements of pH, absence of heavy metals, the magnitude of the refractive index, stability, absence of pyrogenic substances, it must be sterile, almost inert and essentially not contain monomers.

Getting 1.1

Synthesis of hydrogel in an appropriate case, consists of the following operations:

1. Prepare two mixtures A1 and A2. A1 contains water, acrylamide, N,N'-methylene-bis-acrylamide and N,N,N',N'-tetramethylethylenediamine (TEMED). A2 consists of water and ammonium persulfate.

2. These two mixtures are combined in such proportions: 1990 ml A1 and 10 ml A2; incubated at 45°and Tegaserod nitrogen for 20 sec.

3. The reaction mixture was poured into several laboratory beakers (100 ml).

4. Conduct polymerization for 0.5 to 1.5 hours

5. The gel is removed from the mold.

6. The remaining monomers are extracted by means of balancing with WFI-water for 92 hours, changing the water several times, usually 8 times for 92 hours

7. Purified gels homogenized by grinding on the grid, performing oscillatory motion in the vertical direction.

8. Fill the syringe gomogenizirovannykh gel-like material.

9. The syringe is sterilized in an autoclave.

A common way to obtain a hydrogel can be summarised as follows:

Getting 1.2

Crack the E. a statement of the way. The gel is prepared by mixing an aqueous solution of monomers of acrylamide (AM) and N,N'-methylene-bis-acrylamide (BISAM)used as a crosslinking agent, N,N,N',N'-tetramethylethylenediamine (TEMED) as coinitiator, and ammonium persulfate (APS), used as an initiator of free-radical polymerization (redox system). By degassing the solution with nitrogen begin the polymerization. After polymerization, the gel is transferred to a washing tank with trays made from mesh material that is placed gel. During washing with water, the gel swells, and the remainder of the monomer extracted. The swollen gel is served and is injected into the device for filling, where the gel filled syringe, which is subjected to autoclave sterilization.

Get two different elements with low and high final viscosity. Both categories have a solids content of less than 3.5 wt.% and complex viscosity in the range from 2 to 50 PA·usually from 3 to 20 PA·C.

Table 1
Chemical componentLow final viscosityHigh final viscosity
Acrylamide502 g547 g
N,N′-methylene-bis-acrylamide2.2 g 4.6 g
TEMED3.0 g2.6 g
Persulfate ammonium (APS)to 5.4 g5.0 g
Pyrogen-free waterAdd 10 lAdd 10 l

Shown above methods are typical to obtain a hydrogel and can be adjusted within certain limits.

Getting 1.3

Polyacrylamide hydrogels obtained in the process of stitching on the automatic line

A particularly interesting method of obtaining hydrogels according to this invention includes the process of stitching at the entrance. Two separate and completely degassed stream, one of which is a premix acrylamide, methylene-bis-acrylamide (cross-linking agent) and TEMED, and the other is a solution of the initiator APS pumped into a static mixer for mixing, chemical initiation and subsequent extrusion forth in a tubular reactor made of Teflon or steel, in which polymerization occurs. Washing gel is simplified due to the large surface area of the gel from the reactor.

By selection of the concentration of monomer, crosslinking agent and initiator, and their molar ratios and by regulating the speeds of the two flows and the temperature of the polymerization it is possible to obtain gels that distinguish the I degree of crosslinking and solids content.

Getting 1.4

The reagents are mixed in the ratios shown in tables 2, 3 and 4, washed as described in the tables (pyrogen-free water, unless otherwise indicated) and get hydrogels with low, medium and high viscosity. Get hydrogels with a solids content of from 0.5 to 25 wt.% polyacrylamide.

Table 2

The process parameters and characteristics of the obtained gel compositions with low viscosity (lv)
lv1lv2lv3lv4lv5lv6lv7dlv8e
Time lavage (h)a)19,573,759294,372,893,693,9
Dry matter content (%)2,552,082,632,872,893,153,683,17
2,362,58 to 2.672,822,903,573,52
2,09
The molar ratio AM:BISAMb)9767004883663239488488
Molar ratio (AM+BISAM): TEMED252252253251252249252252
Molar ratio (AM+BISAM): APS298299298298298299298298
The remaining monomer (m-1)C)8952,97251,40,97
Elasticity G' (PA) 0,165,2314,3226,657,0571,739,228,5
20,1
Viscosity (PA·)0,0450,882,354,379,111,56,294,55
3,30
The formation of the gel (min)LiquidA liquid with high viscosity122222,52,5
Table 2 (continued)
lv9lv10lv11lv12lv13
Time lavage (h)12196,4#x0200A;
Dry matter content (%)2,18(5,10)f(10,2)f(10,1)f(20,2)f
The molar ratio AM:BISAM701701488488488
Molar ratio (AM+BISAM):TEMED2522522525042016
Molar ratio (AM+BISAM):APS2982982985962385
The remaining monomer (m-1)0,97
Elasticity G' (PA)28,511,1(911)g(1240)gViscosity (PA·)4,551,8(145)g(197)g(1505)g
The formation of the gel (min)3,170,001,213,5h

(a) the substance was liquid, so that the washing was dilution;

(b) infinitely large value;

(C) because the washing was not the extraction and dilution, the content of the remaining monomer was just reduced in accordance with the dilution factor (508 million-1up to 254 million-1);

(d) filling in forms and washing is carried out using a 0.9% aqueous NaCl;

(e) fill it with water; the washing is carried out using a 0.9% aqueous NaCl;

(f) the value to the washing - washing usually reduces these values to 30-55%;

(g) the values before rinsing rinsing is usually to reduce these values by 20-40%;

(h) highly sensitive to the incision;

(i) changes in values may be due to the methods of measurement or location of the party from which the sample was collected.

Table 3

The process parameters and properties of the obtained gel formulations with medium viscosity (mv))
mv1mv2mv3mv4mv5
Time lavage (h)97of 211.59694,890,3
Dry matter content (%)3,142,493,253,293,22
The molar ratio AM:BISAM310310290289289
Molar ratio (AM+BISAM):TEMED252252252251252
Molar ratio (AM+BISAM):APS299299299299299
The remaining monomer (m-1 )1,61,5
Elasticity G' (PA)108,5129133,5
Viscosity (PA·)17,420,621,30
The formation of the gel (min)2,52,52,18
Table 4

The process parameters and properties of the obtained gel composition with a high viscosity (hv))
hv1hv2hv3hv4hv5
Time lavage (h)119,551612295,5of 116.7
Dry matter content (%) 3,472,5of 3.563,833,42
The molar ratio AM:BISAM260260260260260
The molar ratio of (S+BISAM):TEMED315315604313314
The molar ratio of (S+BISAM):APS376376755375376
The remaining monomer (m-1)0,2
Elasticity G' (PA)343274314,5
Viscosity (PA·)54,743,6550,1
In EMA gel formation (min) 2,182,187,5

Example 1A (optional)

Extraction of residual monomers by washing lumps of gel WFI-water ("water for injection")

In table 4A below shows the change in the content of residual monomers in the lumps of gel in the washing pyrogen-free "water for injection" in the process of obtaining a pilot batch of gel Aquamid®according to the invention.

Presents data for the pilot batch SR, except for the value in the initial (zero) point in time, which are calculated (content of dry solids, based on the method) or measured (residual acrylamide) in similar experiments SR and SR. The ratio of the gel/water is about 1:10.

Table 4A
The water change time (hours)The content of dry solids in lumps of gel, wt.%Residual acrylamide in lumps of gel, ppm
05,111001
16n/an/a
24n/an/a
40n/an/a
483,323,6
64n/an/a
722,94,6
88n/an/a
922,72,3
1401,41,1
n/d - not determined

Example 2

Analysis of hydrogel

Characteristics of the hydrogel

The washed hydrogel will have the characteristic properties shown in table. 5.

Table 5
DescriptionOption with a low viscosityVersion with high viscosity
The density of the stitching0,25%0,40%
The amount of swelling80-120%50-70%
Rheological elastic modulus, G' (PA)10-80 PA250-700 PA
Rheological complex viscosity, η*(PA·)2-10 PA·50-90 PA·
Dry matter content (%)the 1.6-3%3-5%
Refractive index1,335-1,3381,338-1,340

Example 3

Swelling occurs during% the fools washing and will typically give the profile of swelling, as shown in figure 2 and 3.

Example 4

Route of administration for the treatment of reflux esophagitis

Treatment by injection

Make the injection of polyacrylamide hydrogel (with a solids content of 2.5 wt.% and pyrogen-free water, about 97.5 wt.%) under the mucous membrane of the trachea or connecting channels of the stomach in such a way as to provide an increased density of the channel. Treatment with a short time-consuming procedure, involving a small number of complications.

Example 5

The method of injection of the hydrogel for contouring

Treatment with injections

(a) injection of the gel can be performed under local anesthesia;

(b) the procedure should be performed under sterile conditions. The gel should not inetservices pharmaceuticals;

(C) gel, which is pre-filled sterile syringe 1 ml syringe with Luer tip cemented tip, should be administered subcutaneously thin grooved needle, for example, 27 g Needle must be CE-marked;

(d) enter the required amount of gel subcutaneously opposite way, inhazinue gel during the reverse movement of the needle. Label for recording patient data is part of the package, you can remove and attach to the patient's medical history, in order to provide monitoring of the use of the product;

(e) after the injection can be done easy and the processing with the aim to obtain a uniform or desired distribution of the gel. Put the gel should form a stable and a soft segment in the connective tissue and lead to satisfactory from the cosmetic point of view of appearance for a long period of time;

(f) possible additional courses of injections to achieve the desired effect.

Treatment by implantation

The gel in the shell of silicone (not sealed) placed under the skin in the soft tissue of the patient.

Example 6

The method of injection of the hydrogel for the treatment of reflux esophagitis

Treatment by injection

Make the injection of polyacrylamide hydrogel (with a solids content of 2.5 wt.% and pyrogen-free water, about 97.5 wt.%) under the mucous membrane of the canal between the esophagus and stomach, for example, to strengthen the sphincter, thereby to provide an increased density of the channel. Treatment with a short time-consuming procedure, involving a small number of complications.

Example 7

The method of injection of the hydrogel for contouring

(a) injection of the gel can be performed under local anesthesia;

(b) the procedure should be performed under sterile conditions. The gel should not inetservices pharmaceuticals;

(C) gel, which is pre-filled sterile syringe 1 ml syringe with Luer tip cemented tip, should be administered subcutaneously thin calibrated and the Loy, for example, 27 g Needle must be CE-marked;

(d) enter the required amount of gel subcutaneously opposite way, inhazinue gel during the reverse movement of the needle. Label for recording patient data is part of the package, you can remove and attach to the patient's medical history, in order to provide monitoring of the use of the product;

(e) after the injection can be done easy processing with the aim to obtain a uniform or desired distribution of the gel. Put the gel should form a stable and a soft segment in the connective tissue and lead to satisfactory from the cosmetic point of view of appearance for a long period of time;

(f) possible additional courses of injections to achieve the desired effect.

Treatment by implantation

The gel in the shell of silicone (not sealed) placed under the skin in the soft tissue of the patient.

Example 8

Route of administration for filling soft tissue

(a) injection of the gel can be performed under local anesthesia, but for the correction of wrinkles and folds of local anesthesia is not required. If lip augmentation is recommended conduction anesthesia;

(b) the procedure should be performed under sterile conditions. The gel should not inetservices pharmaceuticals;

(C) gel, which pre-pre-filled, sterile the haunted syringes 1 ml syringe with Luer tip cemented tip, it should be injected subcutaneously thin grooved needle, for example, 27 g Needle must be CE-marked;

(d) enter the required amount of gel subcutaneously opposite way, inhazinue gel during the reverse movement of the needle. Label for recording patient data is part of the package, you can remove and attach to the patient's medical history, in order to provide monitoring of the use of the product;

(e) after the injection can be done easy processing with the aim to obtain a uniform or desired distribution of the gel. Put the gel should form a stable and a soft segment in the connective tissue and lead to satisfactory from the cosmetic point of view of appearance for a long period of time;

(f) possible additional courses of injections to achieve the desired effect.

Postoperative procedures

If there is swelling, you can topically apply ice. Not recommended for direct sunlight, excessive cold or heat, until then, until you resolve the initial swelling and will not redness.

Unpleasant effects/Side effects of

Patients usually experience pain during the first 2-3 postoperative days. In some patients, possibly some swelling for the first 2-3 days after the injection.

Correct injection technique is a critical factor d is I the final result of the treatment, and the injections should be performed by personnel who have been given the right to do it.

The gel is sterilized (e.g., steam or autoclave). In cases where the packaging is damaged or opened, sterility may be compromised and the contents of the packages should be discarded. Re-sterilization is not recommended.

Example 9

Experience of application in the clinic for filling soft tissue

(1) Correction of the face using the gel was performed approximately 900 patients. The overall cosmetic results were excellent and frequency of the adverse events were 0.02% (Kovanskaya VA; Scientific conference, 13-16 October 2000).

(2) a total of 150 adults were subjected to the correction of facial defects by treatment with injectable gel. The amount of gel, which was introduced by injection, ranged from 0.2 to 11 ml

Provided by the schedule of treatment the patient visits took place on the day of the test (three days prior to day 0), day 0 (first injection), 7-day, 28-day, 3 months, 6 months, and at the end of the study after 12 months, and during these visits, patients were subjected to an objective examination, conducted tests, vital signs, pregnancy tests, did a blood test and serum reactions, hematological and immunological tests, urine analysis, conducted concomitant therapy, analysis of side effects and t is response consideration of the beauty of the patient and surgeon, as well as the filling of the questionnaire, in accordance with the schedule in table 6.

Results

General assessment of the results of the surgery was from very good to good, both patients and surgeons. In some cases, patients wanted to continue treatment and to receive additional injections. Several surgeons voluntarily indicated in the questionnaire that the patients were satisfied with the result, and that the gel is easy to operate and easy to enter the patient.

The gel was very well-tolerated. It was registered only a few cases of side effects, and patients reported that there were adverse side effects - swelling and inflammation, which in a few days resorbed by themselves.

Table 6
Screening (not less than 3 days)Day 0 (facial)Day 7±1 dayDay 28±2 days3 months ±7 days6 months ±7 days12 months ±7 days
before surgeryafter surgery
information/consent based on full information ×
objective examination××××××
the performance of the vital functions×××
pregnancy test×
analysis of blood and serum responsesampling×××
Hematologysampling×××
immunologysampling×××
urine analysis×ÈA; ××
concomitant treatment×××××××
side effects and phenomena××××××
the questionnaire (complaints)××××××
cosmetic result
patient××××
surgeon××××

Example 10

The route of administration and the clinical results of treatment of urinary incontinence

Treatment by injection

Polyacrylamide hydrogel (containing ohoho balance 2.5% and pyrogen-free water approximately 97.5%) inyeccion under the mucous membrane of the urethra, thus, in order to provide increased density of the urethra; the procedure is short and gives little complications.

The technique involves the injection of polyacrylamide gel under the mucous membrane of the urethra of women suffering from incontinence. The injection is performed via the external surface of the urethra and towards the submucosa of the. Inject 3 ml of hydrogel in three places located in the same position in the longitudinal direction of the urethra. The portions are injected at a distance of 0.5 cm from the bladder neck.

Injections are performed under local anesthesia, then allowing the bladder to be filled, and the patient to cough to install it immediately, does sufficient density to hold urine. In the absence of the effect of the injection can be repeated, as is customary in the treatment of injection.

A survey of women showed that treatment with injections is acceptable according to the standards and conditions of the Department of obstetrics and gynecology, Copenhagen Amstsygehus (County hospital) With. The results of the treatment and any complications control verification examinations, which are conducted every three months for one year after treatment.

1. Biologically stable hydrogel for use as end the prosthesis, consisting essentially of the following components: polyacrylamide, which includes a polymer of acrylamide, cross-linked methylene-bis-acrylamide, in which the acrylamide and methylene-bis-acrylamide are connected in a molar ratio of from 150:1 to 1000:1, where the hydrogel is washed with water or saline solution so as to contain about 0.5 to 3.5 wt.% polyacrylamide, counting on the total weight of the hydrogel, and water or aqueous solution, where the hydrogel contains less than 50 hours/million monomers of acrylamide and methylene-bis-acrylamide, and where the elastic modulus of the hydrogel is from about 10 to 700 PA, and its complex viscosity is from about 2 to 90 Pas·C.

2. The hydrogel according to claim 1, where the hydrogel contains at least 95 wt.% water or aqueous solution, counting on the total weight of the hydrogel.

3. The hydrogel according to claim 1, in which polyacrylamide main chain of the polymer has the formula [S3H5NO)]X.

4. The hydrogel according to claim 1, containing at least 1 wt.% polyacrylamide, counting on the total weight of the hydrogel.

5. The hydrogel according to claim 1, the complex viscosity is from about 5 to 80 PA·C.

6. The hydrogel according to claim 1, the elastic modulus which is not less than 20 PA.

7. The hydrogel according to claim 1, the modulus of elasticity is from about 35 to 480 PA.

8. The hydrogel according to claim 1, in which the density of the polymer network is about 0.2 to 0.5%.

9. The hydrogel of claim 1, wherein the acrylamide and methylene-bis-acrylamide are connected at a molar ratio of 175:1 to 800:1.

10. The hydrogel according to claim 1 for use as implantable endoprosthesis.

11. The hydrogel according to claim 1 for use as an injectable implant.

12. The hydrogel according to claim 1, the complex viscosity of which ranges from 6 to 40 PA·C.

13. The hydrogel according to claim 1 for use as implantable endoprosthesis containing shell silicone-based.

14. The hydrogel according to claim 1, which contains 0.5 to 3.4 wt.% polyacrylamide calculated on the total weight of the hydrogel.

15. Prosthesis for filling soft tissue, where the prosthesis is an injectable soft tissue, consisting essentially of the polymeric hydrogel, with specified polymer hydrogel contains less than 50 hours/million Monomeric units, water or an aqueous solution and at least 0.5 wt.% polyacrylamide and less than 3.5 wt.% polyacrylamide, based on the total weight of the polymer hydrogel, where the specified polyacrylamide obtained by a process comprising combining acrylamide and methylene-bis-acrylamide and washing with water or saline solution, so that the content of polyacrylamide is at least 0.5 wt.% and less than 3.5 wt.%.

16. The prosthesis according to 15 in which the polymer hydrogel contains at least 0.5 wt.% high the and calculated on the total weight of the polymer hydrogel.

17. The prosthesis according to 15, in which polyacrylamide main chain of the polymer has the formula [S3H5NO]X.

18. The prosthesis according to 15 containing about 1.9 and 2.9 wt.% polyacrylamide calculated on the total weight of the polymer hydrogel.

19. The prosthesis according to 15 in which the polymer hydrogel contains at least 95 wt.% water or aqueous solution calculated on the total weight of the hydrogel.

20. The prosthesis according to 15 in which the polymer hydrogel contains at least 1.5 wt.% polyacrylamide calculated on the total weight of the polymer hydrogel.

21. The prosthesis according to clause 15, the complex viscosity is from about 2 to 100 PA·C.

22. The prosthesis according to 15 for at least one of the following types of surgery: cosmetic or reconstructive surgery of the face, contouring or filling and reconstructive surgery of the lips.

23. Prosthesis on p.22 for cosmetic or reconstructive surgery of the face, the complex viscosity is from about 2 to 20 PA·C.

24. Prosthesis on p.22 for contouring, the complex viscosity is from about 5 to 50 PA·C.

25. The prosthesis according to article 22 of the filling or reconstructive surgery of the lips, the complex viscosity is from about 2 to 10 PA·C.

26. The prosthesis according to 15 for use in the correction of facial defects caused by at least one the th of the following reasons: aging, acne, trauma, surgery, infection, or congenital deformities.

27. The prosthesis according p, where the correction of facial defects are selected from the group consisting of correction of Malar bones, the correction of nasolabial folds, correction gloomy faces on the bridge of his nose, correction of the depressed shape of the mouth, chin correction, correction of the size or shape of the lips and correction of other defects of the soft tissues of the face.

28. The prosthesis according to 15, in which water is pyrogen-free.

29. The prosthesis according to 15 in which the polymer hydrogel contains less than 20 hours/million of monomer units.

30. The prosthesis according to 15, in which the modulus of elasticity of the polymer hydrogel is at least 10 PA.

31. The prosthesis according to 15, in which the modulus of elasticity of the polymer hydrogel is from about 10 to 700 PA.

32. The prosthesis according to 15, in which the modulus of elasticity of the polymer hydrogel is from about 35 to 480 PA.

33. The application of the hydrogel, which can be obtained in several stages, including combining acrylamide and methylene-bis-acrylamide, initiating radical polymerization and washing with water or saline solution so that the content of polyacrylamide is at least 0.5 wt.% and the content of the polymer is less than 3.5 wt.%, calculated on the total weight of the hydrogel, for receiving the implant for filling soft tissue putaminal mammals, moreover, the complex viscosity of the endoprosthesis is 2-90 PA·and the modulus of elasticity ranges from 35 to 480 PA.

34. Use p to get the implant for correction of cosmetic or functional defect of the person by injection, and complex viscosity of the endoprosthesis is 2-90 PA·and the modulus of elasticity ranges from 35 to 480 PA.

35. Use p to get the implant for correction of cosmetic or functional defect of the lip by injection, and complex viscosity of the endoprosthesis is 2-90 PA·and the modulus of elasticity ranges from 35 to 480 PA.

36. Use p to get endoprosthesis for contouring.

37. Use p, where the implant is a prosthesis for the correction of facial defects resulting from aging, acne, trauma, surgery, or congenital deformities.

38. Use p, where the implant is a prosthesis for the correction of Malar bones, nasolabial folds, correction gloomy grimaces over the bridge, the bulged shape of the mouth or chin, for the treatment of wrinkles, folds, asymmetrical face, or to change the shape of the nose.

39. Use p, where the implant is a prosthesis for the correction of the size or shape of the lips.

40. The use according to any one of p-39, where the endoprosthesis is a crack and the correction of aesthetic defects, due to congenital, traumatic or age.

41. The use according to any one of p-40, where combining acrylamide and methylene-bis-acrylamide conduct when a molar ratio of 150:1 to 1,000:1.

42. The use according to any one of p-41, where the hydrogel contains less than 3.5 wt.% polyacrylamide, based on the total weight of the hydrogel, cross-linked methylene-bis-acrylamide, and at least 95% pyrogen-free water or saline solution.

43. The use according to any one of p-41, where the hydrogel contains at least 1 wt.% polyacrylamide, based on the total weight of the hydrogel.

44. The use according to any one of p-41, polyacrylamide where the main chain of the polymer has the formula [S3H5NO]X.

45. The use according to any one of p-41, where the complex viscosity of the hydrogel is from 6 to 60 PA·C.

46. The use according to any one of p-45, where the concentration of acrylamide and N,N'-methylene-bis-acrylamide in the hydrogel is less than 50 hours/million

47. The application of paragraph 41, where the molar ratio is from 225:1 to 600:1.

48. A method of filling the soft tissues, including the injection of the hydrogel, which is produced in several stages, including combining acrylamide and methylene-bis-acrylamide, initiating radical polymerization and washing of the hydrogel pyrogen-free water or saline solution so that the result is the actual content of the polyacrylamide is at least 0.5 wt.% and the content of the polymer is less than 3.5 wt.%, calculated on the total weight of the hydrogel; and the specified polymer hydrogel contains less than 50 hours/million monomer unit, its modulus of elasticity is from about 10 to 700 PA and a complex viscosity of the hydrogel is from about 2 to 90 Pas·C.

49. An endoprosthesis that includes a hydrogel for the treatment of urinary incontinence or anal incontinence, and specified the hydrogel contains from about 0.5 to 25 wt.% the polymer obtained by the process comprising combining acrylamide and methylene-bis-acrylamide, washing the hydrogel pyrogen-free water or saline solution, where the specified hydrogel contains less than 50 hours/million Monomeric units, and where the complex viscosity of the specified hydrogel is from about 2 to 90 Pas·and the modulus of elasticity is from about 1 to 200 PA.

50. The application of 49, where for the treatment of urinary incontinence implant is introduced into the urethra or neck of the bladder.

51. The application of 49, where the polymer is produced by combining acrylamide and methylene-bis-acrylamide in a molar ratio of 150:1 to 1,000:1.

52. The application of 49, where the hydrogel contains less than 15 wt.% polymer calculated on the total weight of the hydrogel.

53. The application of 49, where the hydrogel contains at least 1 wt.% polymer calculated on the total weight which the hydrogel.

54. The application of 49, where the main chain of the polymer has the formula [S3H5NO]X.

55. The application of 49, where the complex viscosity of the hydrogel is about 2-40 PA·C.

56. The application of 49, where the hydrogel contains at least 80 wt.% water or aqueous solution.

57. The application of 49, where the introduction includes the injection of the hydrogel.

58. The application of 49, where injecting hydrogel includes injection in positions corresponding to positions 10, 2 and 6 hours on the clock, around the axis of the cross-section of the urethra to treat urinary incontinence, or injections of provisions corresponding to the provisions of 10, 2 and 6 h on the dial of the clock, around the axis of the transverse section of the colon or rectum.

59. The application of 49, where the hydrogel contains less than 10 wt.% polymer calculated on the total weight of the hydrogel.

60. The application of 49, where the hydrogel contains less than 7.5 wt.% polymer calculated on the total weight of the hydrogel.

61. The application of 49, where the hydrogel contains less than 5 wt.% polymer calculated on the total weight of the hydrogel.

62. The application of 49, where the hydrogel contains less than 3.5 wt.% polymer calculated on the total weight of the hydrogel.

63. The application of 49, where the hydrogel contains at least 1.5 wt.% polymer calculated on the total weight of the hydrogel.

64. The application of 49, where the complex viscosity of the hydrogel SOS is to place approximately from 2 to 50 PA· C.

65. The application of 49, where the complex viscosity of the hydrogel is from about 2 to 30 PA·C.

66. The application of 49, where the crosslinking agent is a methylene-bis-acrylamide.

67. The application of 49, where the polymer consists essentially of cross-linked polyacrylamide.

68. The application of 49, where the polymer consists essentially of a polymer obtained by polymerization of acrylamide in the presence of a crosslinking agent.

69. Use p, polyacrylamide where the main chain of the polymer has the formula [S3H5NO]X.

70. The use of hydrogel containing 0.5-25 wt.% polyacrylamide calculated on the total weight of the hydrogel to obtain a prosthesis for the treatment or prevention of urinary incontinence.

71. The use of hydrogel containing 0.5-25 wt.% polyacrylamide calculated on the total weight of the hydrogel to obtain a prosthesis for the treatment or prevention of anal incontinence.

72. The application of the hydrogel obtained in several stages, including combining acrylamide and methylene-bis-acrylamide in such amounts that the content of the polymer is from about 0.5 to 25 wt.% calculated on the total weight of the hydrogel, the initiating radical polymerization and washing pyrogen-free water or saline solution, to obtain a prosthesis for the treatment or prevention of urinary incontinence.

73. Use geroge what I produced in several stages, including combining acrylamide and methylene-bis-acrylamide in such amounts that the content of the polymer is from about 0.5 to 25 wt.% calculated on the total weight of the hydrogel, the initiating radical polymerization and washing pyrogen-free water or saline solution, to obtain a prosthesis for the treatment or prevention of anal incontinence.

74. The application of the hydrogel obtained in several stages, including combining acrylamide and methylene-bis-acrylamide in such amounts that the content of the polymer is from about 0.5 to 25 wt.% calculated on the total weight of the hydrogel, the initiating radical polymerization and washing pyrogen-free water or saline solution, to obtain a prosthesis for the treatment or prophylaxis vesicoureteral reflux in mammals.

75. The use according to any one of p-74, polyacrylamide where the main chain of the polymer has the formula [(C3H5NO]X.

76. The use according to any one of p-75, where the module of the complex viscosity of the hydrogel is from about 2 to 50 PA·with, for example, from about 2 to 40 PA·C, preferably from about 2 to 30 PA·s, more preferably from about 2 to 20 PA·C.

77. The use according to any one of p-76, where the modulus of elasticity of the hydrogel is from about 1 to 200 PA, the example from about 2 to 175 PA, usually about 5 to 150 PA, more preferably from about 10 to 100 PA.



 

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1 ex

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2 tbl

FIELD: petroleum processing industry, in particular, cleaning of petroleum and petroleum product transportation pipelines and separation of media.

SUBSTANCE: composition contains polyacrylamide, petroleum product, mineral acid salt, linking agent, powdered formaldehyde derivative, and sweet water.

EFFECT: increased efficiency in pressurizing cavity of pipeline having various diameter and steep turnings during cleaning thereof and separating of media.

5 cl, 1 tbl

FIELD: polymer production.

SUBSTANCE: invention provides composition for preparation of gradient hydrogel polymer material based on copolymers of acrylamide and N,N'-methylene-bis-acrylamide representing following system: (i) mixture of dilute solution containing 2-3% acrylamide, 0.1-0.2% N,N'-methylene-bis-acrylamide, 0.01% ammonium persulfate, and, as viscosity regulator, 0.5-2.0% glycerol or 1:1 mixture of glycerol and polyvinyl alcohol, each taken in amount 3.5-8.0%, in bidistilled water and (ii) and concentrated solution containing 6-45% acrylamide, 0.6-1.0% N,N'-methylene-bis-acrylamide, and 0.04% ammonium persulfate in bidistilled water, said dilute solution constituting 75-80% and said concentrated solution 20-25% of the total weight of the system. Components are distributed in gradient manner in final system. Invention also discloses a method of preparing gradient hydrogel polymer material based on above-indicated copolymers and indicated gradient hydrogel polymer material. Value and direction of gradient of modulus of elasticity of hydrogel polymer materials is controlled by concentration of viscosity regulator.

EFFECT: expanded possibilities for preparing gradient hydrogel polymer materials.

3 cl, 1 tbl, 8 ex

FIELD: production of new materials.

SUBSTANCE: proposed nanocomposite can be used as component contributing to charges of consumer properties of materials made on its base. Nanocomposite includes fibrils of filler-chitin individualized to nanosizes with distance between fibrils from 709 to 20-22 nm and water-soluble polymeric matrix in interfibril space. Degree of filling of nanocomposite is 0.05-0.25% mass. Fibrils are arranged in parallel and they have cross size of 4 nm. Method of production of nanocomposite comes to the following: free-radical polymerization in water medium of at least one monomer of row of acrylic acid, salt of acrylic acid, acrylamide is carried out in presence of filler. Initiator is chosen from the row of water-soluble peroxides, hydroperoxides or their salts, potassium persulfate. Individualization to nanosizes of fibrils is done simultaneously with process of polymerization and/or with combination of said process with mechanical disintegrating action by disintegrating or pressing, or pressing with abrasion shift. Nanocomposite is obtained in form of film, being pervaporation membrane.

EFFECT: enlarged range of filling, ease of production.

22 cl, 1 tbl, 9 ex, 2 dwg

FIELD: polyacrylamide composition used as flocculating agent in textile, paper, food processing industry, oil production, coal benefication, wastewater treatment, etc.

SUBSTANCE: claimed composition contains (wt.%) polyacrylamide 0.5-0.7; 0.15-0.35 stabilizing agent (e.g., organic low molecular aliphatic dichlorides); and balance: water.

EFFECT: polyacrylamide flocculating agents of improved storage stability.

3 ex, 3 dwg, 1 tbl

FIELD: polymer production.

SUBSTANCE: invention relates to water-soluble powder polymer compositions useful as flocculants for dehydration of solids-containing slurries or sludges. Compositions are prepared via continuous polymerization of at least one unsaturated monomer, wherein at least one polymerization-affecting parameter is varied in accordance with a repetitive scheme. For instance, monomer concentration, molecular weight regulator amount, monomer solution pH value, and/or monomer solution composition can be varied.

EFFECT: expanded flocculation possibilities and reduced sensitivity to composition of fluids to be treated.

14 cl, 4 ex

The invention relates to polymer chemistry, more specifically, firstly, to water-soluble copolymers containing in the structure a nitrogen atom, secondly, to get in solid form, easy grinding and easily soluble in water compositions based on water-soluble Homo - and copolymers containing in the structure a nitrogen atom, thirdly, to a method for producing compositions of water-soluble Homo - and copolymers

The invention relates to a composition and method for producing a non-ionic and anionic water-soluble polymers in the form of finely dispersed particles of the polymer in aqueous salt environment

FIELD: polymer production.

SUBSTANCE: invention relates to a method for production of high-molecular weight water-soluble polymers used as flocculant at enterprises of water conditioning, petroleum processing, petrochemistry, iron and nonferrous metallurgy, paper-and-pulp, varnish-and-paint, chemical, and other industries. In particular, invention provides a method for production of high-molecular weight (meth)acrylic anionic flocculant via copolymerization of water-soluble anionic ethylenically unsaturated monomer with nonionic ethylenically unsaturated monomer, the former being salt of (meth)acrylic acids and the latter (meth)acrylic acid amide and ester at salt/amide/ester ratio 100:10:(1-6) or 100:(1-6):10. Proposed method leads to production of high-molecular weight (meth)acrylic anionic flocculant in the form of powder with nearly 100% content of principal substance, which is well dissolved in water.

EFFECT: enhanced efficiency in treatment of various disperse systems (industrial effluents).

3 cl, 4 tbl, 4 ex

FIELD: polymer production.

SUBSTANCE: invention provides composition for preparation of gradient hydrogel polymer material based on copolymers of acrylamide and N,N'-methylene-bis-acrylamide representing following system: (i) mixture of dilute solution containing 2-3% acrylamide, 0.1-0.2% N,N'-methylene-bis-acrylamide, 0.01% ammonium persulfate, and, as viscosity regulator, 0.5-2.0% glycerol or 1:1 mixture of glycerol and polyvinyl alcohol, each taken in amount 3.5-8.0%, in bidistilled water and (ii) and concentrated solution containing 6-45% acrylamide, 0.6-1.0% N,N'-methylene-bis-acrylamide, and 0.04% ammonium persulfate in bidistilled water, said dilute solution constituting 75-80% and said concentrated solution 20-25% of the total weight of the system. Components are distributed in gradient manner in final system. Invention also discloses a method of preparing gradient hydrogel polymer material based on above-indicated copolymers and indicated gradient hydrogel polymer material. Value and direction of gradient of modulus of elasticity of hydrogel polymer materials is controlled by concentration of viscosity regulator.

EFFECT: expanded possibilities for preparing gradient hydrogel polymer materials.

3 cl, 1 tbl, 8 ex

FIELD: chemical industry, chemical technology, polymers.

SUBSTANCE: invention relates to a method for preparing aqueous polymer dispersions of the multipurpose designation. Method for preparing an aqueous dispersion of styrene-acryl copolymer is carried out by preliminary emulsifying a mixture of acrylic monomers with styrene in the presence of emulsifying agent and the following aqueous-emulsion co-polymerization of the reaction mixture in the presence of initiating agent. Monomer mixture comprises additionally acrylamide, and method involves using ammonium persulfate and hydrogen peroxide as an initiating agent. Method involves the successive fractionally dosing feeding ammonium persulfate for two stages followed by addition of a mixture of polymethylsiloxane of molecular mass 55-1000 Da and iron sulfate in their mass ratio = (25-35):1 to the reaction mixture at stirring, cooling the reaction mass and its neutralization to pH = 5-6. Invention provides preparing the stable aqueous polymeric dispersion with diminished size of particles. Invention provides enhancing strength and water resistance of film prepared on its base.

EFFECT: improved preparing method.

1 tbl, 3 ex

FIELD: paper-and-pulp industry.

SUBSTANCE: : process comprises preparation of paper pulp, flocculation of pulp, shear force-involving mechanical treatment of pulp, second flocculation of pulp, drainage of pulp on the screen to form sheet, and subsequent drying of sheet. Flocculation is carried out by adding water-soluble optionally having intrinsic viscosity above 3 dl/g. Polymer is further characterized by oscillation delta tangent value at 0.005 Hz above 1.1.

EFFECT: improved drainage and retention on moving screen, and formation process.

10 cl, 1 dwg, 4 tbl, 4 ex

The invention relates to polymer chemistry, more specifically, firstly, to water-soluble copolymers containing in the structure a nitrogen atom, secondly, to get in solid form, easy grinding and easily soluble in water compositions based on water-soluble Homo - and copolymers containing in the structure a nitrogen atom, thirdly, to a method for producing compositions of water-soluble Homo - and copolymers

The invention relates to compositions (K) for polymerization immobilization of biological macromolecules in the hydrogels in the formation of biochips TO=andA+b+withC+dD+eE, including the a - monomer based on the derivatives of acrylic and methacrylic acids; water-soluble crosslinking agent; With modified biological macromolecule containing unsaturated group, D is a water - soluble compound as the component environment for copolymerization; E - water, where a, b, C, d, e - the percentage (X) of each component in the composition (X= m/v100% solids and X=v/v100% for liquid substances), in which the total content of monomer and crosslinking agent lies in the range of 3-40% (3(a+b)(40), the ratio of monomer and cross-linking agent is within 97: 3-60:40, and the percentage of components C, D and E is in the range of 0.0001%10%; 0%d90%; 5%E.

The invention relates to methods of producing synthetic low molecular weight polyelectrolytes are polymers and copolymers (M<1,5106on the basis of a number of acrylamido, the macromolecules which contain groups capable of ionization in solution, is used as the dispersant aqueous suspensions, stabilizers of emulsions, additives for drilling in extreme conditions, when creating an artificial soil structure

The invention relates to methods of producing synthetic high molecular weight polyelectrolytes are polymers and copolymers on the basis of a number of acrylamido, the macromolecules which contain groups capable of ionization in the solution used in the purification of natural and waste waters, for flotation, as additives for drilling in extreme conditions, when creating an artificial soil structure

The invention relates to the manufacture of paper, and more particularly, to a method of making paper, which paper add weight cationic organic polymer containing a hydrophobic group and an anionic material microecology

FIELD: medicine, in particular tubular polyurethane articles (guides, suction drainages, catheters) having aseptic coat.

SUBSTANCE: claimed articles are produced by providing of article elements followed by assembly thereof and application of aseptic coat by impregnation of catheter surface with chlorohexidine and/or salts thereof (e.g., dihydrochloride, or diacetate, or bigluconate, etc.), by article treatment for 14-180 min with aqueous-alcohol solutions of chlorohexidine and/or salts thereof at 20-60°C, containing (mass %): chlorohexidine and/or salts thereof 1-5; ethanol or methanol 75-85; water 15-25.

EFFECT: prolonged anti-microbial activity; protection against body contamination during catheterizing.

5 cl, 1 tbl

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