In-situ system for intra-articular regeneration of cartilaginous and bone tissues
SUBSTANCE: invention refers to medicine. What is described is an implanted multilayer chondral reparation flap showing biological compatibility and physiological resorption, and what is also described is a method providing surgical management in situ for intra-articular regeneration of cartilaginous tissue in joint damages and/or defects. The chondral reparation flap comprises a first external cell-impermeable layer and a second external cell-permeable layer adapted for placement in an immediate proximity from a subchondral bone on a wound portion, and also a cartilage-forming matrix located between the first and second layers. The cartilage-forming matrix represents an accepting medium for diffusion of autologous stem cells and contains chemical components promoting formation of a hyaline-like cartilage in the presence of said autologous stem cells. The method prevents a fibrous cartilaginous replacement tissue from forming within the injury region.
EFFECT: method provides autologous compositions which when used in a combination with the reparation flap form the medical system for formation of the replacement hyaline-like intra-articular cartilage.
17 cl, 7 dwg, 1 ex
The technical field to which the invention relates.
The present invention relates to compositions for therapeutic purposes, providing biological effects and contains components that are connected in the form of layers. More specifically, the present invention relates to compositions, in physical form adapted for surgical implantation or introduction into a living organism. More specifically, the present invention relates to such compositions in which the surgical implant or material subject to destruction, resorption or dissolution.
The level of technology
One of the tasks of medicine, including in the area of surgery is to restore health lost due to injury or disease. Surgery is the search for increasingly effective ways of treatment on cartilage defects. Such defects of the joints (vnutribryushnye defects) can occur for a variety of reasons, including injury and disease, such as osteoarthritis. Hyaline articular cartilage is a specialized connective tissue of the body, having the properties and perform the function of maintaining the weight and shock absorption. Injury or loss of this specialized connective tissue in the joints leading to pain and dysfunction of the joint.
Although hyaline cartilage and has some ability to the novostroiki, but it is very limited. Therefore, in the field of orthopedic surgery there is a reason for the development of treatment methods by which replacement of damaged hyaline cartilage or which contribute to its regeneration. This is the answer of medicine on a large number of joint injuries that happen every year, and the growing number of older people with joint problems. Typically this treatment presents pure surgical methods, which remove dead tissue and produce mechanical damage restoration, with or without added into the injury area, active compositions that promote wound healing or prevent inflammation/infection.
Recently, in order to ensure proper healing of the industry attempts of treatment methods, which arose under the influence of bioengineering, such as autologous tissue flaps. However, presented the injury, in which there is a combination of damage to bone and cartilage, present a difficult therapeutic challenge, and in many cases still does not have therapeutic compositions and methods of treatment that would have been satisfactory in all respects. For example, certain surgical procedures for dissecting osteochondritis that use transplants what I autologous chondrocytes, require a long period of cultivation of cells and their growth, as well as multiple operations. In addition, such treatments often lead to the development of fibrous cartilage replacement tissue that is a bad substitute hyaline articular cartilage. Cm. J. Kramer and others, Cell. Mol. Life Sci., 63, 616-626 (2006).
Therefore, in this industry it is useful to have an alternative method of treatment of bone and cartilage injuries, which does not require cell culture and does not result in injury fibrous cartilage replacement tissue. Moreover, it is desirable that the resulting replacement fabric was a natural helenoftroy articular cartilage.
Disclosure of inventions
The present invention is an in situ system, contributing to the treatment/tissue growth, as well as the method of using hyaluronic acid nonhuman origin and autologous mesenchymal stem cells for regeneration vnutriarterialnah cartilage damage. More precisely, the proposed system and method, which stimulate the growth galanopoulou cartilage in situ with the purpose of correcting defects vnutriarterialnah cartilage. To this end, the system corresponding to the invention, contains healing cartilage repair graft consisting of a composition of natural hyaluronic acid and matrix from ragenovich fibers, in which additionally embedded growth hormones and/or growth factors, as well as the composition Diacerein and/or Rhein. This use of autologous mesenchymal stem cells obtained by microfractures tissue to the subchondral bone in the process of setting cartilage repair graft, as an element of the specified system to build cartilage and bone tissues in vnutriarterialnah defects.
Corresponding to the present invention implanted multilayer cartilage repair graft is a surgical tool that has biological compatibility and property physiological resorption, for in situ regeneration of cartilage tissue in vnutriarterialnah damage. Cartilage repair graft is layered or multi-layered tool. This tool contains the underlying or bottom layer adapted for placement with a fit to the area of bone to be treated. This layer is permeable to cells" in the sense that it allows the cells to migrate from the site of the wound and move through it. On top of the underlying layer is a layer haseorunemanga matrix, which is closely linked with postludium layer. Gradiometry matrix is a collagen layer and is acceptrules environment for the maps in the AI autologous stem cells and other blood components at the site of the wound. Layer matrix includes chemical components that contribute to the formation of galanopoulou cartilage in the presence of autologous stem cells. Also, if desired, the top layer can more or less play the role of a barrier layer, for example, not allowing to pass through it to the cells, but letting other small objects, such as small molecules, water and gases. All these elements combined give plastic biocompatible material that is capable of physiologically to dissolve and which is relevant to the present invention a multilayer cartilage repair graft.
Brief description of drawings
Figure 1 represents a cross-section of the subchondral bone, depicting hondaline/presented damage where there is no section of the cartilage covering the solid part of the bone.
Figa is a cross-section corresponding to the present invention sterilized, plastic multilayer cartilage repair graft, detail showing the structure of the matrix of the flap, in which collagen and hyaluronic acid are placed in the form of fibers.
FIGU is a cross-section corresponding to the present invention sterilized, plastic multilayer x is Asiago repair of the flap, detail showing the construction of the internal matrix of the flap, in which the collagen is placed in the form of fibers and hyaluronic acid in the form of cramptons suspension or visco-elastic solution.
Figs is a cross-section corresponding to the present invention sterilized, plastic multilayer cartilage repair graft, showing the lower and upper layer, with both layers have the function of ensuring that the flap mechanical strength.
Fig.2D is a cross-section corresponding to the present invention sterilized, plastic multilayer cartilage repair graft, which shows a variant containing only the lower layer performs the function of securing the flap mechanical strength.
File is a cross-section corresponding to the present invention sterilized, plastic multilayer cartilage repair graft, which shows a variation in which the lower layer performs the function of securing the flap mechanical strength.
Figure 3 depicts the General scheme of the main stages of the method corresponding to the present invention.
Figa, 4B are a cross-section characteristic of the site of the wound and illustrate the first stage of site preparation wounds reception is shown plastic multilayer cartilage repair graft: (A) the application of micro-damage or perforations on the surface of the subchondral bone; and (C) the formation of a blood convolution of local bleeding, caused by micro-damage.
Figure 5 is a cross-section characteristic of the site of the wound and illustrates the second stage corresponding to the present invention method: application to the site of the wound "fibrin glue"enriched autologous serum.
Figa is a cross-section characteristic of the site of the wound and illustrates the overlapping plastic multilayer cartilage repair graft to the site of the wound on top of the clot of fibrin glue/blood.
6 represents a cross-section characteristic of the site of the wound and illustrates the migration of mesenchymal stem cells and other blood components that appear in response to wound formation of blood convolution in 'fibrin glue to form the composition of the blood folds/fibrin glue.
Figs is a cross-section characteristic of the site of the wound and illustrates the migration of mesenchymal stem cells and other blood components that appear in response to wound formation, composition of blood folds/fibrin glue later in the matrix of cartilage repair graft.
Fig.7 is a cross-section characteristic of the site of the wound and gives the final form of the treated area after resorption of cartilage p is Aracinovo flap and transformation of the site into the bone and/or galanopoulou cartilage.
The implementation of the invention
On the accompanying drawings in graphic and schematic form presents embodiments of the present invention. In the drawings, identical elements are denoted by the same numbers, with like elements are denoted by the same numbers, but with a different subscript.
As shown in figure 1, one of the problems faced in this area is how to promote the regeneration of cartilage tissue in the area of 6 defects or injuries (cartilage damage), that is, tissue regeneration, as it is possible more close to the natural cartilage 8, which is adjacent to the specified area and which otherwise covers the subchondral bone 4 in section 6. This is especially important in areas of RAS, where the captures and damage the cartilage and bone.
As shown in figa-2E, the subject of the present invention is an implantable cartilaginous repair flap 10, which has biological compatibility and property physiological resorption and which in situ promotes regeneration of cartilage tissue in vnutriarterialnah hondaline or presented damage 6 (see figure 1). Corresponding to the invention of the cartilage repair patch 10 is a sterilized plastic multi-layer material 12, which may be implanter the Academy of Sciences in the area of 6 wounds and which can contribute to the regeneration galanopoulou cartilage. Task cartilage repair graft 10 is to stimulate growth galanopoulou cartilage in situ after arthroscopic or open surgical overlay flap 10 patients with hondaline or presented by the damage. An additional challenge is that the cartilage repair patch 10 was biologically erodible due to the interaction of its components with collagenase and other proteases and that time was dissolving and disappearing.
Multi-layered material 12 cartilage repair graft 10 in turn is built entirely from materials that possess biological compatibility and property physiological resorption, so this cartilage graft can be implanted to a patient without subsequent removal, and may eventually disappear from the site of implantation. In one embodiment of the invention, the multilayer material 12 cartilage repair graft contains the first upper (barrier) layer 16 and the second bottom or underlying porous layer 22. Cm. figa-2C. In another preferred embodiment, the material 12 cartilage repair graft consists of two layers: the underlying layer 22 and a layer 30 of a matrix. Cm. fig.2D-2E. Underlayment is designed for contact with the surface of the bone at the site 6 is Ana. And the underlying layer 22 and the top layer 16 is made of collagen sheet (see Angele and other U.S. patent 6737072, the content of which is incorporated into this description by reference). An example of a suitable source of industrial supplies collagen sheet is XENODERM™, Biometrica AG, Switzerland. On the porous spreading layer 22 is a layer 30 haseorunemanga matrix. Layer 30 haseorunemanga matrix provides a collagen substrate, detecting mesenchymal stem cells, but also creates an environment to support the growth of cells, in which these cells will grow and will be their differentiation into chondrocytes in the presence of other natural components of the layer 30 of the matrix.
In a preferred embodiment, the layer 30 of the matrix is a sterile or sterilized collagen composite plate with woven fibers 36 inhuman collagen and natural fibers 40 of hyaluronic acid. Natural collagen is obtained from a source inhuman nature - used porcine, bovine or vegetable collagen. Natural hyaluronic acid (ha) derived from a natural source, by nature not associated with mammals, for example, by bacterial fermentation or by extraction from cocks ' combs. Among the other titles of the civil code which may be used are the following: sodium salt of hyaluronic acid, sodium hyaluronate. In the matrix 30 natural GK can be represented in the form of fibers 40 natural Ledger, as shown in figa, or in powder form 40A ha gel or creamy suspension 42, distributed in free space among collagen fibers 36, as shown in figv.
In a preferred embodiment, the composite gradiometry matrix 30 includes one or more hormones (e.g. growth hormone) growth of tissue and/or stimulants 46 growth factor.
Stimulants growth factor are chemical compounds that increase the expression of growth factor at the site. In the present embodiment, stimulants growth factor are Diacerein 46a and Rhein 46b. In the embodiment presented on FIGU, suspension 42 also contains Rhein 46b and/or Diacerein 46a. The weight ratio of collagen to the General Ledger should be in the range of about 0.1:to 99.9 to 50:50 when the molecular weight of natural Ledger from 0.5 to 6 million daltons. The concentration of Diacerein or Rhein must be in the range of approximately 10 to 50 µmol when they are added to the matrix in the form of powder or in the form of gel or cream Ledger containing Diacerein or Rhein. Other songs, which presumably can be entered into the matrix layer 30 include compositions of chitosan (Chitosan) and the composition of the lactic acid polymer (Poly-actic Acid).
Autologous mesenchymal stem cells 60, originating from a source which is external to the cartilage repair patch 10, is diffused into the flap 10 through the porous spreading layer 22 and into the layer 30 of the matrix, where they are supported fibrous components (collagen fibers 36 and/or fibers 40A ha) matrix 30. Fiber 40 and 40A of the matrix provide stem cell substrate for their growth and differentiation in chondrocytes. Exogenous factors 46 growth, such as Diacerein, inhibit the parameters of inflammation (e.g., cytokines: IL-1, TNF-alpha and free radicals), which contribute to inflammation and destruction of cartilage. Diacerein stimulates the production of certain growth factors such as TGF-β, which additionally will stimulate the production of components of cartilage, such as General Ledger, collagen type II and proteoglycans (including aggrecan). Growth hormone will stimulate the production of cartilage and bone tissues. In addition, the composition 54 fibrin glue is added to endogenous factors 50 growth of autologous serum fraction that stimulates the differentiation of stem cells 60 on the border of the bundle of blood/flap. The cumulative effect of these interactions leads to growth galanopoulou cartilage.
Figure 3 summarizes diagram illustrating the main steps is sushestvennee way relevant to the present invention. In a preferred embodiment, the method comprises three stages: stage 100 site preparation wounds; stage 120 preparation and application of fibrin glue; and stage 140 overlay cartilage repair graft. At step 100, as part of the preparation, manufacture fence patient blood samples and receive autologous serum fraction. Autologous serum fraction is used as the source of the first components for wound healing, such as TGF-β, and will be added during implantation in fibrin glue in the area of 6 wounds. Data endogenous components will enhance the differentiation of mesenchymal stem cells.
Also at this stage produce microfracture/perforating the surface of the subchondral bone to cause local bleeding 58, which covers the area of 6 wounds fresh blood. Cm. figa. To cause local bleeding 58 on the surface 14 of the subchondral bone can be a number of ways. In a preferred embodiment, presented on FIGU, site preparation available chandralekha or presented the damage carried out by applying micro destructions or perforations 56 to the surface 14 of the subchondral bone 4, often associated with scraping solid bone. As shown in the figure, the microfracture/perforation/scraping 56 Subhan the Federal bones 4 causes bleeding 58 in the area of 6 wounds. Blood 58, falling on the area of 6 wounds, contains autologous mesenchymal stem cells 60 and other healing components, redundant tissue of the subchondral bone 4 in response to microfracture, perforation and scraping 56.
As shown in figv, blood 58, which covers the area of 6 wounds, entails the formation on the specified plot convolution 59 blood. In the system corresponding to the present invention, a technique is used microfractures to cause bleeding and stimulate the release of autologous mesenchymal stem cells (MSCS), and growth factors in a bundle 59. Data pluripotent MSCS in the presence of the considered cartilage repair graft 10 will differentiate into chondrocytes and extracellular create helenoftroy gradiometry matrix for repair/replacement of existing chandralekha/presented damage 6.
After section 6 of the wound will be prepared, carry out the second step 120 of the method corresponding to the present invention. This stage 120 consists in the preparation and application of fibrin glue 54 on blood folds 59 section 6 wounds. As shown in figure 5, fibrin glue 54 is mixed with fresh blood bundle to form a combined clot 54-59 of blood convolution/fibrin glue. However, the known and the other is the means of placing fibrin glue 54 in place, which correspond to the present invention, and in practice may be selected by the specialists in this field of knowledge. For example, the cartilage repair patch may be sewn into place (not shown).
After application of fibrin glue 54 on the site of the wound carry out the third step 140 of the method corresponding to the present invention. This third stage 140 consists of placing a plastic multi-layer repair of the flap 10 at the site of the wound over a combined clot 59/54 of fibrin glue/blood convolution section 6 wounds. On figa plastic multilayer cartilage repair graft 10 superimposed on a plot of 6 wounds. After setting the repair of the flap 10 in place, also can be a free way applied fibrin glue 54 to additionally stick repair patch 10 to section 6 of the wound. Upon completion of this stage is completed and surgical operations corresponding to the present invention, and cartilage repair graft 10 continues to perform its therapeutic function in situ.
As shown in figv, mesenchymal stem cells and other blood components that appear in response to injury of the blood convolution 59 migrate into the fibrin glue 54. Figs shows how it continues further migration of mesenchymal stem cells and other blood components that appear in the em to trauma, combined clot 59/54 fibrin glue/blood convolution through the porous outer layer 22 in the layer 30 matrix cartilage repair of the flap 10. In the layer 30 of the data matrix mesenchymal stem cells and autologous growth factors interact with the components of cartilage repair of the flap 10. The presence of these components is explained by diffusion of the convolution 59 gradiometry matrix 30 repair of the flap 10. The barrier layer 16 cartilage repair graft 10 is temporarily prevents further diffusion of these various compositions in the joint gap. Conversely, the movable components of the layer 30 matrix can migrate from cartilage repair graft in a mass of fibrin clot 54 and then into the blood folds 59 on the surface 14 of the subchondral bone 4.
Diacerein 46a and Rhein 46b inhibit the production and activity of Pro-inflammatory cytokines, such as IL-1β, nitric oxide, free radicals and matrix metalloproteinases, which are all involved in the inflammation and destruction of cartilage, particularly in the joints affected by osteoarthritis. This Diacerein 46a and Rhein 46b stimulate the production of growth factors such as TGF-β, which in turn stimulate the expression of cartilage components such as hyaluronic acid, proteoglycans, aggrecan and collagenase type II, in which the e are important components haseorunemanga matrix.
Growth hormone will stimulate the growth of cartilage and bone tissues. Over time, as shown in Fig.7, the cartilage repair patch 10 is resorbed, and the defective area 6 relatively quickly transformed into a more physiological, helenoftroy cartilage 90.
Collagen cartilage repair graft
For the bottom layer 22 was used collagen sheet 22 (Xenoderm - pork collagen types 1 & 2). The bottom layer had mechanical properties sufficient for the shear and tensile force, and could dissolve, and in about 6 weeks. Collagen sheet 22 was placed in a mold and then filled the collagen-SC suspension, to which was added either to the solution of Diacerein, or powder Diacerein to get in the flap concentration of 5-50 µm dry weight after lyophilization and sterilization.
The result has been a two-layer collagen plate, the bottom layer which is designed for direct placement on the bone surface. After fabrication, but prior to sterilization, the plates were placed in a mechanical press to obtain a thickness of 0.5-2 mm, the concentration of SC in the dried final product was in the range of approximately from 0.1% to 2%. Ledger was a natural GK, that is, chemically unmodified GC, obtained by fermentation.
The advantage of this is th invention is the fact that what is suggested remedy and treatment that will best promote regeneration of damaged articular cartilage.
Another advantage of the present invention is that the proposed treatment and the means are presented for damage that does not require cell culture.
Another advantage of the present invention is that for this kind of damage is proposed treatment and remedy, which does not result in the damage site fibrous cartilage replacement tissue.
And another advantage of the present invention is that the proposed treatment and the tool that best guarantee that the resulting replacement tissue will be a natural helenoftroy articular cartilage
Although this description contains many specific details, these should not be seen as parts limit the invention, but as examples of those or other preferred embodiments of the invention. There are many other options, obvious to a person skilled in this field. Accordingly, the scope of the invention should be determined by the content of the items included formulas and cash equivalents, and not a variant embodiment of the invention.
1. Implantable physiologically rassasyvanii multilayer gradev the second flap repair,
the first outer layer,
second permeable outer cell layer adapted for placement at the site of the wound in close proximity to the subchondral bone, and
haseorunemanga matrix located between the first and second outer layers, with the specified gradiometry matrix is acceptrules environment for the diffusion of autologous stem cells, and gradiometry matrix is biocompatible and physiologically rassasivaniem composite material, including natural hyaluronic acid and collagen, and promotes the formation galanopoulou cartilage in the presence of these autologous stem cells.
2. Implantable repair patch according to claim 1, characterized in that the collagen haseorunemanga matrix essentially consists of collagen inhuman origin.
3. Implantable repair patch according to claim 1, characterized in that the first outer layer, a second outer layer, or both the outer layer consists of collagen sheet.
4. Implantable repair patch according to claim 1, characterized in that the first outer layer, a second outer layer, or both the outer layer consists of a porcine collagen (Xenoderm®).
5. Implantable repair patch according to claim 1, characterized in that the natural hyaluron the traveler acid haseorunemanga matrix, essentially, consists of natural hyaluronic acid inhuman origin.
6. Implantable repair patch according to claim 1, characterized in that the natural hyaluronic acid is presented in the form of fibers, powder, gel or creamy suspension.
7. Implantable repair patch according to claim 1, characterized in that gradiometry matrix embedded chemical composition, promote the regeneration of cartilage.
8. Implantable repair patch according to claim 7, characterized in that the chemical composition, promote the regeneration of cartilage, contains one or more compounds selected from the group of compounds comprising: a growth factor, diacerein, failure to comply, polylactic acid and chitosan.
9. Physiologically rassasyvanii multilayer cartilage repair graft that has biological compatibility, for in situ regeneration of cartilage tissue in vnutriarterialnah damage, consisting of:
the underlying permeable layer made of collagen sheet, and
haseorunemanga matrix, located on the underlying layer, representing permeable collagen composite plate with woven fibers inhuman collagen and natural hyaluronic acid in the form of fibres of natural hyaluronic acid or hyaluronic acid powder the OIC acid in a gel or creamy suspension, distributed in the free space among the collagen fibers.
10. The repair patch according to claim 9, characterized in that the collagen haseorunemanga matrix consists essentially of a porcine, bovine or vegetable collagen.
11. The repair patch according to claim 9, wherein the underlying layer comprises porcine collagen (Xenoderm®).
12. The repair patch according to claim 9, characterized in that the natural hyaluronic acid haseorunemanga matrix essentially consists of natural hyaluronic acid derived from a natural source, by nature not associated with mammals.
13. Repair flap in claim 11, characterized in that the natural hyaluronic acid haseorunemanga matrix consists essentially of natural hyaluronic acid nonhuman origin, obtained by bacterial fermentation.
14. The repair patch according to claim 9, characterized in that gradiometry matrix embedded chemical composition, promote the regeneration of cartilage, which contains one or more compounds selected from the group of compounds comprising: a growth factor, diacerein, failure to comply, polylactic acid and chitosan.
15. Method of in situ vnutriarterialnah regeneration of the cartilage tissue at the site vnutriarterialnah wound of a patient, providing ispolzovaniem multilayer cartilage repair graft according to claim 1 or multilayer cartilage repair graft according to claim 9, which impose specified cartilage repair graft in the proper orientation on top of a layer of a clot of fibrin glue and blood, created on the site of the wound, cover the area of the wound and allow the cartilage repair patch to initiate growth galanopoulou cartilage on the specified site of the wound, with subsequent resorption of cartilage repair graft.
16. The method according to item 15, wherein the cartilage repair graft is sewn in place.
17. The method according to item 15, wherein the fibrin glue mixed with blood obtained from the zone microfractures/scraping on the site of the wound, while thrombin fraction of fibrin glue in the proportions 50/50 replaced centrifuged autologous serum and the clot of fibrin glue and the blood placed on the surface of the wound under the cartilage reparation flap for sealing wounds and obtain a mechanically strong structure.
SUBSTANCE: porous matrix based on biocompatible polymer or polymer mix for tissue engineering is obtained by compression of polymer and sodium chloride particle mix with defined particle size, and further removal of sodium chloride by dissolution. Porosity grade of matrix lies within 93 to 98%, its pores fall into different sizes, with definite pore distribution by size within certain limits.
EFFECT: obtained matrices are free-shaped yet pertain stability and hardness characteristics required to withstand surgical implantation methods and counteract mechanical forces applied at the implantation point.
40 cl, 2 tbl, 8 ex
SUBSTANCE: present group of inventions concerns medicine, more specifically coated implants and devices. There is offered ceramic composition-precursor for making high-strength bio-elements used as an absorbable or partially absorbable biomaterial where the composition contains at least one silicate with Ca as a base cation with the absorption rate less or equal to the bone growth rate, and this at least one silicate acts as a base binding phase in a biomaterial, and this at least one silicate Ca is present in amount 50 wt % or more, and all other components if any are presented by additives, such as an inert phase, and/or additives which make a biomaterial to be radiopaque. There is offered hardened ceramic material which is based on the ceramic composition-precursor and is in the hydrated form. There is offered a medical implant, application of the medical implant, and also a device or a substrate coated with the uncured ceramic composition-precursor and/or hardened ceramic material.
EFFECT: invention provides a biomaterial having initial and constant durability which is dissolved in due time and reacts with an organism to generate a new tissue.
29 cl, 1 ex, 3 tbl
SUBSTANCE: invention relates to field of medicine. Claimed is composition with hyaluronic acid (HA), which includes gel particles of bound water-insoluble hydrated HA. HA includes bindings, represented with the following structural formula: HK'-U-R2-U-TK'. Where each group HA' represents the same or other molecule of bound HA'; each U independently represents optionally substituted 0-acylisourea or N-acylurea; and R2 represents optionally substituted alkyl, alkenyl, alkinyl, alkoxy, cycloalkyl, cycloalkenyl, cycloalkinyl, aryl, heteroaryl, heterocyclic radical, cycloaliphatic alkyl, aralkyl, heteroaralkyl or heterocyclolalkyl. Also claimed is method of developing tissues in individual, including introduction of needle into individual in place where development of tissues is necessary, needle is connected to syringe filled with composition with HA, and applying force to syringe in order to supply composition with HA to individual. Method of obtaining composition with HA includes formation of water-insoluble dehydrated particles of bound HA, separating insoluble in water particles by their average diameter, selection of subset of particles by average diameter and hydration of subset of dehydrated particles by means of physiologically compatible water solution. Other method of obtaining composition with bound HA includes binding precursor of bound HA by means of bis-carbodiimide in presence of pH buffer and dehydration of bound HA. Also included is method of developing tissues in individual that needs tissue development. Method of stabilisation of bound HA includes hydration of water-insoluble dehydrated bound HA by means of physiologically compatible water solution which includes local anesthetic, so that value of elasticity module G' for stabilised composition constitutes not less than approximately 110% from value G' for non-stabilised composition.
EFFECT: claimed composition of hyaluronic acid and method of preparation and application of HA composition are efficient for development of tissue and/or drug delivery.
27 cl, 22 ex, 2 tbl, 7 dwg
SUBSTANCE: effect is achieved by using compositions based on different stereoregular amorphous biodegradable polymers - polylactides and copolymers of lactides with glycolides (18-72 mass ratio) as the second component of biocompatible mineral filler - hydroxyapatite with particle size of the main fraction of 1-12 mcm (8-41 mass ratio), as well as an organic solvent with boiling temperature equal to or higher than softening temperature by 3-20°C (20-41 mass ratio). After preparation of a homogenous mixture, the composition is undergoes thermal treatment at 80-130°C in a vacuum in a shaping vessel with the required shape. A porous product is obtained due to removal of solvent. Density of the obtained porous product is about 0.4-0.8 g/cm3.
EFFECT: design of a method of obtaining porous biodegradable composite polymer products based on polylactides or copolymers of lactides and gylcolides.
3 cl, 3 ex
SUBSTANCE: described are implants based on biodegradable thixotropic compound with pseudo-plastic properties and implant injected under skin or into skin in fibrous tissue. Containing microparticles of at least one biocompatible ceramic compound in suspension, in at least one liquid carrier containing at least one compound based hyaluronic acid and at least one biodegradable thixotropic compound with pseudo-plastic properties. Also disclosed is kit for preparation such implants directly before application, as well as implant production and using for filling of crinkles, and/or skin cavity, and/or cicatrices.
EFFECT: implants of simplified injection.
14 cl, 4 ex
SUBSTANCE: thin-film multichamber structure, made of collagen is used as an element for tissues regeneration, thus it is possible to enhance the stimulation of regeneration, to reduce treatment period, to accelerate the functional recovery and to achieve similar effects with regard to body tissues such as nervous tissue, subdermal tissue submucosa tissue, membranous tissue, adipose tissue, muscle tissue, skin tissue and gum tissue. Moreover, when the structure is used for patients with neuropathic pain, it leads to disappearance of pain.
EFFECT: obtaining new structure made of collagen to increase the stimulation of regeneration of nerve tissue, healing and regeneration of the soft biological tissue having defects, etc without the use of laminin, or nerve growth factor (NGF), and an element for the regeneration of tissue, including it.
12 cl, 21 dwg, 12 ex
SUBSTANCE: membrane to be used in targeted angiogenesis comprises a plate made of undemineralised or demineralised type I collagen prepared from spongy bone tissue and saturated with sulphated glycosaminoglycans, heparin and chondroitin sulphate. In dental implantation, it includes at least one hole.
EFFECT: application of the invention in targeted angiogenesis.
1 tbl, 3 ex
SUBSTANCE: group of inventions refers to pharmaceutics and medicine and concerns method of producing bioabsorbable matrix containing native nonreconstructible collagen type I, same bioabsorbable matrix used for filling defected soft and hard tissues, as implant, also method of treatment, reparation or replacement of tissue with using the disclosed bioabsorbable matrix bioabsorbable matrix. Method of producing the bioabsorbable matrix includes after treatment of animal skin; herewith derma treated with aqua-alkali solution containing sodium hydroxide, potassium dihydrogen phosphate and aqueous or anhydrous borax at temperature 1 to 10°C; herewith derma treated with aqueous solution of sodium sulphate and sodium hydroxide; herewith derma treated with aqueous solution of sodium sulphate; herewith derma treated with aqueous solution of boric acid. At the third fourth and fifth stages the derma is treated with periodic agitation of the solution periodically cooled to temperature 1 to 10°C; and each stage two to five includes water flushing of derma to ensure neutral pH of rinsing water.
EFFECT: invention ensures production of bioabsorbable matrix containing native nonreconstructible collagen type I with collagen fibre structure identical to natural collagen-containing tissue, possesses considerable mechanical properties and is applied as a matrix for growth, directional regeneration, improvement of soft and hard tissue trophism and structures.
32 cl, 1 ex, 3 dwg
SUBSTANCE: bone of natural origin is cleaned, sawed up to 0.2-2.0 cm thick plates, washed with heated to 65°C 0.1 M pH 5.8-6.0 phosphate buffer, digested in 0.1-0.4% activated papain solution at 65°C during 24 hours, then washed in five volumes of water at 40-80°C, treated with 0.4 N alkali at room temperature during 10-24 hours, rinsed in running water, degreased in ethanol/chloroform mixtures in ratio 1:2 firstly, and 2:1 secondly, decalcified in 0.4-1 N hydrochloric acid, treated with 1.5-3% hydrogen peroxide during 4 hours, washed with purified water, then with ethanol, dried at room temperature, packed up and sterilised. Material for osteoplasty and tissue engineering represents compound, in which native collagen matrix space structure and natural bone mineral component are preserved, containing 25% collagen and 75% mineral matter. According to dry material analysis it includes less than 1% non-collagen proteins.
EFFECT: method improvement.
3 cl, 5 ex
SUBSTANCE: method of biomedical material production based on titanium and cobalt alloy in mode CBC includes as follows. Exothermal mixture of raw reagents made of powdered titanium and cobalt is prepared, added with max. 4 wt % titanium hydride and max. 15 wt % amorphous nanodisperse powdered calcium hydroxyapatite (CHA) or nanocomposite calcium hydroxyapatite with biopolymers. This powdered raw mixture is pressed to preparation blanks placed to reactor CBC. Preparation blank is preheated to temperature 350-580°C. Combustion action is initiated in inert atmosphere with following release of end product. Produced biomedical material represents mushy alloy of formula TiCo of total porosity 55-70% at open porosity portion 90-98% with prolate pores sized 200-800 mcm. Pore partitions are also porous with prevailing round pores of diameter ca 100 microns. Surface of mushy alloy is coated with calcium, phosphor and oxygen compounds which are hydroxyapatite decomposition products with prevailing content of calcium perovskite.
EFFECT: material is noncytotoxic, cells are characteristically split and actively migrate inside of mushy space.
4 cl, 4 dwg, 3 ex
SUBSTANCE: collagen tubes can be used for connection and regeneration of damaged nerves. Tube is formed of single sheet of collagen-containing material. Sheet has smooth small-sized external barrier surface preventing connecting tissue from growing through it. Tube also has internal sift fibrous surface which helps nerve to grow at higher speed.
EFFECT: higher speed of regeneration of damaged nerves' prevention of scars.
18 cl, 4 att, 4 dwg
SUBSTANCE: bone-and-mineral product contains porous bone mineral particles produced from natural bone and having crystalline structure practically corresponding to natural bone structure and practically containing no endogenous organic material. The particles have fibers of physiologically compatible type II resorbable collagen at least on their surface. Mass proportion of type II collagen fibers and porous bone mineral is at least equal to approximately 1:40.
EFFECT: enhanced effectiveness in recovering combined injuries of cartilage and bone tissue in articulations having defects.
8 cl, 6 dwg
SUBSTANCE: the present innovation deals with the method to accelerate mucosal healing due to the following technique: one should apply a membrane consisted of purified collagenic material obtained out of natural collagen-containing tissue onto the part of affected mucosa to provide the chance for mucosal reconstruction in this part and, also, it deals with mucosa-regenerating preparation and application of purified collagenic material obtained out of collagen-containing natural tissue for preparing mucosa-regenerating preparation. The innovation provides more modified method that accelerates mucosal regeneration, as a whole, and, particularly, after surgical operations associated with the plasty of oral fornix.
EFFECT: higher efficiency.
12 cl, 3 dwg, 5 ex
FIELD: medicine, ophthalmology.
SUBSTANCE: the present innovation deals with a drainage for treating glaucoma that includes collagen types II-III immobilized in polymer of acrylic and vinyl rows, includes a cytostatic covalently bound with collagen types II-III, hypotensive preparation and not less than one rigidity rib at certain ratio of components. The innovation provides improved ocular hydrodynamics, suppression of reparative and cicatricial processes around the drainage suggested.
EFFECT: higher efficiency.
6 dwg, 3 ex
SUBSTANCE: method involves introducing sharp tip of hollow needle into bone cortical layer crack. The crack is filled through needle lumen by introducing Collapan gel mixed with radiopaque substance in minimum concentration providing radio contrast range excess above injured bone contrast. Soft tissues are pierced with the needle in the vicinity of crack filling area center. Needle bevel plane is set in crack plane projection and introduced into the crack. Then, needle tube is rotated with its bevel plane directed into crack space. The cerebral covering soft tissues are pressed to bone along the crack path above positioned needle tip projection and the mixture is introduced in the amount equal to crack cavity region under pressed sift tissue. The needle end is pulled and directed towards the opposite crack region without removing it from the soft tissues and the region is also filled. Collapan introduction into crack fissure is carried out under X-ray optoelectronic transducer control.
EFFECT: enhanced effectiveness of treatment; reduced risk of postoperative complications.
SUBSTANCE: invention relates to medicine. Described is implant, which can be injected in subcutaneous or intracutaneous way in form of monophase hydrogel, which contains gel, obtained from cross-linked hyaluronic acid and one of its physiologically acceptable salts.
EFFECT: obtaining subcutaneous implant used for filling wrinkles and stimulation of epidermal cells and/or supporting mechanical properties of skin density and elasticity.
15 cl, 2 ex
SUBSTANCE: present invention refers to medicine, more specifically to use of a polymer containing thiol groups, for producing a tissue extension implant where a base polymer is polysaccharide.
EFFECT: polymers containing thiol groups have an antioxidant effect, and are characterised by longed stay on an application site.
13 cl, 4 dwg, 7 ex
SUBSTANCE: what is offered is a method of making a construct containing crystal cellulose. Cellulose-forming organisms are grown at least partially in a hollow template made by means of a three-dimensional printer. What is offered is a method of making the hollow template by means of the three-dimensional printer which grows portions of the hollow template in layers from a modelling material.
EFFECT: invention can be used for making the construct which can be successfully used as an implant or for cultivation of mammal or human living cells.
16 cl, 7 dwg
SUBSTANCE: in a nanostructured bioplastic material containing a native form of hyaluronic acid, a base is nanostructured hyaluronic acid produced by photochemical cross-link and having a cellular texture in the range of 50 to 100 nm.
EFFECT: higher clinical effectiveness of using the bioplastic material ensured by better adhesion and creating the optimal cell migration conditions in a wound.
1 tbl, 1 dwg
SUBSTANCE: invention relates to medicine, namely to medical device, which includes biocompatible medical coating, glued to it, in which coating includes at least one of non-linked water-soluble salts (i) of alginic acid, (ii) hyaluronic acid or (iii) chitosane, coating being completely dissolved in at least one physiological fluid of human organism for less than 3 hours.
EFFECT: coating quickly dissolves from device.
29 cl, 2 tbl, 7 ex