Biomaterials consisting of sulphated hyaluronic acid and hellane applied for prevention of commissures in spine

FIELD: medicine.

SUBSTANCE: novel biomaterials consist of combination of sulphated hyaluronic acid and deacetylated hellane for application as highly efficient barrier for prevention of post-operation commissures in operation in abdominal, pelvic areas and, first of all, on spine.

EFFECT: increase of application efficiency.

16 cl, 1 dwg, 2 tbl, 6 ex

 

The technical FIELD TO WHICH the INVENTION RELATES.

The present invention relates to new biomaterials consisting of a combination of sulfated hyaluronic acid and'gellan (and'gellan, which are not associated with other polymers), for use as a highly effective barrier, preventing postoperative adhesions during surgery in abdominal, pelvic region and, above all, on the spine.

The LEVEL of TECHNOLOGY

The formation of postoperative adhesions is the most common complication that occurs in 70-90% of cases after surgery in the abdominal or pelvic region (Holmdahl L. Et al., Eur. J. Surg. 1997, 163(3):169-174) and with a frequency of up to 40% during operations on the spine (Einhaus SL et al., Spine 1997, 22(13):1440-1447).

Many factors determine and/or affect the formation of postoperative adhesions, such as mechanical trauma, postoperative bleeding, the occurrence of ischemic and inflammatory phenomena and possible microbial infection.

Serous bleed and have exudate, which is formed as a result of surgical trauma, if it is not quickly reabsorbable, may cause a marked recruitment of fibroblasts with subsequent deposition of collagen molecules responsible for the formation of adhesions between adjacent tissues.

In conclusion, it appears that the formation of postoperative adhesions is what I direct consequence of the inflammatory process.

In the field of spine surgery, the formation of epidural fibrosis is a major postoperative risk. In fact, after a laminectomy and/or discectomy fibrous astrocytes (cells characteristic of glia) form a glial scar tissue, the function of which is to prevent leakage of neuronal substance of the dura matrix, the most remote meninges covering the spinal cord, formed by fibrous connective tissue.

This is normal in the healing process of damaged tissues of the spine, but in the postoperative inflammatory process such perfectly inelastic tissue adhesions can occur in excess of and interfere with neuromotor processes of the nerve root and dura matrix, destroy adjacent tissues and anatomical structures, thus making it painful normal movement of the spinal cord and limbs.

Any subsequent operations may be more complex, requiring a longer hospital stay and less optimistic forecasts.

In connection with the foregoing reasons, the prevention and/or suppression of postoperative adhesions, in particular, epidural fibrosis, becomes the main tasks in medical and pharmaceutical research.

The necessary characteristic features of EF is an objective barrier against the formation of adhesions are Biodegradability, and biocompatibility, low toxicity or no, good adhesiveness and manipulation, no obstruction to the natural healing process of damaged tissues, but mainly the ability to prevent adhesions, which may be formed between adjacent tissues subjected to surgery in the abdominal area or on the spine.

Had a lot of different substances (both in vitro and in vivo) as a possible new anti-adhesions, such as synthetic or semi-synthetic membrane made of polyethylene terephthalate (Dacron), methacrylate, polylactic acid (Klopp LS et al., Neurosurg Focus 2004,16(3):E2), polytetrafluoroethylene (type Goretex)(Llado A, et al., Eur Spine 1999, 8(2): 144-150).

In other experiments investigated the influence of the washing steroid or non-steroidal drugs, but these substances do not meet all the necessary requirements (described above) for anti-adhesions, which can effectively and safely be used in clinical practice.

In U.S. patent 5017229, 5527893 and 5760200 described a new type of membrane against adhesions (Seprafilm), consisting of two chemically linked polymers, such as hyaluronic acid and carboxymethylcellulose, however, the effectiveness of the new barrier is reduced due to problems of toxicity associated with the use of activating agents, such as carbodiimide that are necessary for having obrazovaniya chemical bonds between the two polymers.

In U.S. patent 5605938 described medical device against adhesions (ADCON-L), consisting of rasskazyvaemoe and extrudable gel, consisting of pork gelatin and dextran sulfate. The ADCON gel®-L proved to be very effective for the prevention of postoperative adhesions and, for this reason, it was used by the applicant as a control means in the animal experiments described below.

In contrast, in the patent EP 1323436 described a new barrier against adhesions obtained from a combination of carboxymethyl cellulose and'gellan, in a mass ratio of 1:(0.2 to 5). Derivative of cellulose in this case is an active agent in the prevention of adhesions, however, it is known that it did not have anti-inflammatory and/or antimicrobial properties, unlike sulfated hyaluronic acid (SHA) (OR B1), which is the active agent in a new barrier against adhesions, which is the subject of this invention.

Also conducted research with hyaluronic acid, which has not been chemically modified (U.S. patent 4141973), to study its properties as a barrier against adhesions, but since this polymer is easily hydrated and biodegraders, the time of its existence in situ is too short to was the ability to completely prevent the formation of the ration.

For this reason, hyaluronic acid modified with the formation of ester linkages within the molecule (EP 0341745 B1)that make it effective for preventing both abdominal and pelvic adhesions (Hyalobarrier®gel-based ACP®gel) a marked increase in the lifetime of the polymer at the injury site (EP 0850074).

Esters of hyaluronic acid (EP 0216453 B1), in particular the benzyl ester (Hyaff®-11), was effective for the prevention of postoperative adhesions (US 6723709), and also particularly suitable when applied to the manufacture of solid structures, such as felts (EP 0618817 B1).

However, the validity of the modified hyaluronic acid in spine surgery have never experienced.

This invention relates to a new biomaterial derived from a combination of sulfated hyaluronic acid and'gellan, as well as a new biomaterial formed only Gellan polymer. The biomaterials of the invention proved to be highly effective for prevention of postoperative adhesions, as abdominal and pelvic, and is particularly effective for General prevention of adhesions that form after back surgery such as laminectomy and diskectomy.

DETAILED description of the INVENTION

The present invention relates to a new bio is the material, consisting of a combination of sulfated hyaluronic acid or other sulfated derivatives of hyaluronic acid and'gellan, as well as a new biomaterial formed only'gellan, as new medical devices to prevent post-operative adhesions, as abdominal and pelvic, and in particular, adhesions that form after surgery on the spine.

In fact, biomaterials, which represents the present invention was effective to prevent adhesions, which are often formed after surgery laminectomy/discectomy, or as a consequence of various types of operations on the spine.

Found that sulfated hyaluronic acid plays a major role in the prevention of adhesions; in fact, the presence of carboxylate polysaccharide together with its sulfated groups leads to strong electrostatic repulsion relative to fibroblasts, leading, thus, to slow down the cellular invasion of the damaged tissue of the spine. 'gellan, on the other hand, acts as a structural matrix capable of suppressing the absorption of sulfated hyaluronic acid being treated fabrics, at the same time acting as a carrier for biomaterial (preferably in gel form) maintaining its initial consistency over time, while he effectively performs its role as a barrier against adhesions.

Sulfated hyaluronic acid, its preparation and application of the device against adhesions described and claimed in EP 0702699 B1. However, the physico-chemical characteristics of SHA are such that the gel formed only called polymer will have a viscosity comparable to the viscosity, which has not been chemically modified. In fact, it turns out that SHA more easily hydrated than desulfuromonas polysaccharide, and has the same Biodegradability. For these reasons, itself SHA cannot be used as a biomaterial to prevent postoperative adhesions, since the time of its existence in situ it is not enough to prevent adhesions.

On the other hand, it appears that the combination of sulfated hyaluronic acid and'gellan is optimal, since the experiments performed on animals (and subsequently described), show that the formation of fibrous tissue around the meningeal dura membrane matrix is negligible compared to untreated controls as relative to untreated controls, and experiments with the device ADCON®-L (device against adhesions, has long been used in clinical practice), and that, therefore, there are no spikes or LF the development of scar tissue in relation to the dura matrix.

In EP 0702699 B1 describes the new derivatives of hyaluronic acid obtained by the method of sulfation of the polysaccharide, which leads to the formation of molecules sulfated hyaluronic acid (which can be sulfated in varying degrees), with specific anticoagulant and antithrombotic properties, for the manufacture of new medical devices.

In contrast, the applicant has shown that the presence of sulfated groups chemically related to hyaluronic acid in the biomaterial according to the invention does not interfere with the normal blood clotting process.

In addition, the biomaterial of the present invention also has anti-inflammatory and antimicrobial properties, providing, thus, all the characteristics necessary for an effective agent against adhesions.

'gellan is a microbial exopolysaccharide origin, derived from a microorganism Sphingomonas elodea aerobic fermentation. Natural'gellan is heteroglycan resulting binding recurring tetrasaccharide links consisting of glucose, glucuronic acid and ramnose, in the molar ratio 2:1:1.

Diallylammonium'gellan (base hydrolysis) get a commercial product Gelrite®, which is used in the present invention, as the howl or in combination with sulfated hyaluronic acid or its sulfated derivatives.

In its natural state'gellan forms gels that are weak, but elastic and flexible, while deacetylating'gellan in the same conditions forms a dense gels.

'gellan can be applied in the field of food biotechnology and pharmacy. It is used in food and/or feed as a thickener and stabilizer in plant biotechnology as the substrate (solid) for growing bacterial cultures. In the pharmaceutical industry'gellan used in the formation of microcapsules with slow release due to its ability to form gel in the presence of cations.

Hyaluronic acid is heteropolysaccharide, consisting of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. It is a polymer with an unbranched chain with a molecular weight that varies from 50,000 to 13 x 106Daltons (Da), in accordance with the source from which it was received, and methods used to obtain. It is present in nature in the surrounding cage gels, the main substance of the connective tissue of vertebrate organisms (in which she is one of the main components), in the synovial fluid of joints, in the vitreous body and the umbilical cord.

ON plays an important role in the body, especially as mechanical the cue media for the cells of many tissues, such as skin, tendons, muscles and cartilage. In addition, since it is the main component of the extracellular matrix, it plays a role or is involved in other biological functions, such as tissue hydration, lubrication of joints, migration and differentiation of cells.

Due to bio/mucoadhesive properties and compatibility with the tissue hyaluronic acid and its salts (especially sodium, potassium, magnesium and calcium may properly derivateservlet), proposed as a system for controlled release agents, and for the manufacture of medical devices such as prostheses.

ON used in this invention, can be obtained from any source, for example it can be extracted from scallops males (EP 0138572 B1), obtained by fermentation (EP 0716688 B1) or technological ways, it can have a molecular weight in the range from 400 to 3×106Yes, in particular from 10,000 to 1×106Yes, and more specifically, from 100000 to 250000 Yes.

The sulfate crystallization process of hyaluronic acid and its derivatives can be made by the method known to the person skilled in the art, but preferably, as described in EP 0702699 B1.

Derivatives, which can be used in sulfate crystallization method are listed below:

ON in the form of salts with organic and/or reorganizes is their reason, with a molecular mass of 50-730 KDa (EP 0138572 B1) or with high molecular weight 750-1230 KDa (EP 535200 B1); preferably with a molecular mass of from 100 to 250 KDa;

Hyaff, esters with aliphatic alcohols, arylaliphatic, cycloaliphatic, aromatic, cyclic or heterocyclic series (EP 216453 B1); the percentage of esterification of hyaluronic acid, which is then subjected to sulfate crystallization may vary from 5 to 65%, in accordance with the type and chain length used alcohol as the resulting product must be water-soluble;

Billing, internal esters (EP 03411745 B1); the percentage of internal esterification of hyaluronic acid, which is then subjected to sulfate crystallization may vary from 1 to 15%, as the resulting product must be water-soluble;

HyoxxTM, proboscidian derivatives, obtained by the oxidation of primary hydoxyl N-acetylglucosamine part (EP 1339753); the percentage of percarboxylic hyaluronic acid, which is then subjected to sulfate crystallization may vary from 1 to 50%.

All available carboxypropyl ON may form salts with organic and/or inorganic bases.

The degree of sulfate crystallization of hyaluronic acid and/or its derivatives, listed above, in terms of the number of sulfated groups on the repeating element can what sonatica from 0.5 to 3.5 and can be preferably equal to 3.

A number of pharmacologically and/or biologically active substances possibly associated with the main components of the biomaterial of the present invention to increase its effectiveness against adhesions, in particular, antibiotics and medicines that are classified as inhibitors of proteins, such as interleukin (IL)-10, IL-13, IL-1, TNF and interferon.

Device against adhesions according to the invention can be manufactured in various forms: sponges, gels or hydrogels, foams or powders, and the preferred form is a gel or hydrogel.

The mass ratio of'gellan (G) and SHA (or G, and sulfated derivatives ON) can be changed from 1.5:1, 2:1 to 2:1,5, and it is preferable mass ratio of 2:1. Alternatively, as described previously, 'gellan can be used as such, preferably in the form of a gel or hydrogel, as a new biomaterial against adhesions in the spine.

In the following text describes some examples of the preparation of biomaterials of the present invention, active against adhesions, together with the results of in vivo experiments.

Example 1

Obtaining a biomaterial in the form of a hydrogel consisting of'gellan in combination with sulfated ON with the mass ratio2:1

ON sulfation according to EP 0702699 B1 to the extent sulfate crystallization 3./p>

A solution of 20 mg/ml deacetylating'gellan (Gelrite) was obtained by heating (75-85°C) and by dissolving 1 g of'gellan in 50 ml of NaCl at 0.9%. After complete dissolution was added 500 mg of the sulfated ON and left to dissolve. Then the mixture was cooled to room temperature, until then, until he had the hydrogel, which can then be sterilized by steam.

Example 2

Obtaining a biomaterial in the form of a hydrogel consisting of'gellan in combination with sulfated ON with the mass ratiothe 1.5:1

Obtaining carried out as in example 1 by dissolving 750 mg'gellan and 500 mg of sulfated ON.

Example 3

Obtaining a biomaterial in the form of a hydrogel consisting of'gellan in combination with sulfated complex benzyl ether, with a degree of esterification of 25%, with the mass ratio2:1

The solution'gellan was obtained as described in example 1 was then added 500 mg of the sulfated complex benzyl ether and left to complete solubilization. He was then left for cooling to room temperature, thus obtaining a hydrogel, which can then be sterilized by steam.

Example 4

Obtaining a biomaterial in the form of a powder, consisting of'gellan in combination with sulfated ON with the mass ratio2:1

Getting Khujand who have been as in example 1, but after the dissolution of sulfated ON the still warm solution was slowly poured into absolute ethanol, cooled to 4°C. Then the precipitate was separated from the solvent by filtration. The obtained powder was dried using high vacuum system.

Example 5

Obtaining a biomaterial in the form of sponges, consisting of'gellan in combination with sulfated ON with the mass ratio2:1

Obtaining carried out as in example 1. Then the final solution obtained after cooling at room temperature, was subjected to lyophilization cycle. Thus was obtained a three-dimensional structure in the form of a sponge.

Example 6

Obtaining a biomaterial in the form of a hydrogel formed only'gellan

A solution of 20 mg/ml deacetylating'gellan (concentration may vary from 1 to 50 mg/ml) was obtained by dissolution after heating (75-85°C) 1 g'gellan, Kelcogel CG-LA (viscosity of 32 CP) in 50 ml of 0.9% NaCl. Complete dissolution usually occurs within 3-5 minutes. (Time to solubilize the dissolution of the powder'gellan depends on its viscosity, which can vary from 26 to 39 SDR). The solution was left to cool to room temperature until, until I got the hydrogel, which can be sterilized by steam.

Preclinical experiments

Experiments Prov is conducted on laboratory animals, to show the full efficacy and safety of a new biomaterial of the present invention.

Testing devices against adhesions

The biomaterials were tested on laboratory animals, were:

ADCON-L, a medical device in the form of a gel consisting of pork gelatin and sulfated dextran, used as a control proven clinical efficacy against adhesions;

ASR gel, consisting of inner esters with internal esterification of 5%obtained in physiological solution with a concentration of 60 mg/ml;

Gel Hyaff-11, complicated benzyl ether ON with a degree of esterification of 50%obtained in physiological solution with a concentration of 70 mg/ml;

Gel G/SHA formed by the combination of G and SHA received physiological solution with a mass ratio of'gellan to 2:1 (see example 1);

Gel G/CMC-S, consisting of a combination of'gellan and sulfate carboxymethylcellulose (CMC-S)obtained in physiological solution with a mass ratio of 1.5:1;

Gel ASR/SHA formed billing and SHA received physiological solution as the Association between polymers with a mass ratio of 5:1;

Gel'gellan, obtained according to example 6.

Experimental model of education post

adhesions after surgery

Used 24 new Zealand to whom the oliku with an average weight of 2.5 kg Each animal was anestesiologi intravenous solution Zoletil/Rompun/saline (1:0,5:3,5 about./about./about., 0.25 ml/kg); all animals were operated on the lumbosacral level on two separate sections of the spine: L2 and L4.

After the incisions 5 cm along the spinous processes of the corresponding region of the underlying muscle fascia was then cut off any excessive bleeding was stopped by cauterization. Then there was a laminectomy (5×10 mm) at the level of the lumbar vertebrae L2 and L4, thus exposing the dura matrix and the nerve roots that emerge from the spinal cord.

At this stage of the operation used is described above the device against adhesions and muscle fascia, and lying on top of her skin sewed together at the same place.

Three specimens of animals served as negative controls. They operated in the same way, but without receiving any treatment against adhesions to assess the level of adhesion and contraction of fibrous tissue, which is formed in relation to the dura matrix.

Just operated 24 animals on 2 different sites and analyzed 7 devices. Whereas negative controls, each device was tested on 3 animals, have had 6 sections of the spine on each device.

Tests

Prothrombin lie is (RT)

After one month after surgery, all animals were killed. Blood samples were taken from 3 used as negative controls and animals 3 animals, which were subjected to treatment gel G/SHA for 3 days before surgery and on day 21 of treatment for the specific hemodynamic tests (RT) to evaluate any effects SHA clotting comparison of blood from treated animals with the blood of untreated controls (Mennmeyer ST et al., JAMA 1993,269(8):1030-1033).

Histological analyses

Samples were taken from the spinous processes (zone L2 or L4) animals treated with G/SHA, and animals treated with ADCON-L, as well as animals belonging to the negative control group. Then received samples for histological analysis, samples were fixed in 10% formalin, then immersed in decalcifiers solution consisting of a mixture of formalin/nitric acid/distilled water (10/5/85). Then the samples dehydrational in alcohol, immersed in paraffin, then cut into sections of 5 µm thickness and stained with hematoxylin and eosin.

Subsequent analyses detected the formation of fibrous tissue and adhesions from dura matrix presented in terms of scoring after analysis of all samples as follows:

A score of 0 corresponds to the fact that there is fibrous tissue that is present near the dura matrix;

Assessment sootwetstwuet to that is a very thin fibrous tissue, visually prominent between the newly formed scar tissue and dura matrix;

A score of 2 corresponds to the presence of fibrous tissue, tied with dura matrix, affecting nearly 2/3 of the area exposed by a laminectomy;

A score of 3 corresponds to the presence of fibrous tissue, which causes compression and completely fused with the dura matrix, affecting more than 2/3 of the area exposed by a laminectomy.

Anatomical observations

After killing all the animals examined at the site of the laminectomy. Then the dura matrix and nerve roots were again exposed to assess the formation of adhesions and compression in the form of the following system of scoring:

A score of 0 corresponds to the absence of fibrous tissue that is visible near the dura matrix.

A score of 1 corresponds to a thin layer of fibrous tissue, which can be seen unstable welded to the dura matrix.

A score of 2 corresponds to the presence of fibrous tissue, moderately welded with dura matrix.

A score of 3 corresponds to the presence of fibrous tissue, compressing and significantly tied with dura matrix.

A score of 4 corresponds fibrous tissue present in a quantity sufficient to occupy all of the area subjected to surgical operations.

The obtained results

Evaluation of prothrombin time (PT):

Table 1 presents the values of RT samples of blood taken from animals, processing the data G/SHA in comparison with untreated controls.

rawsamples: RT measured at3 daysbefore surgeryrawsamples: RT measured after28 daysafter surgeryprocessedsamples: RT measured at3 daysbefore surgeryprocessedsamples: RT measured after28 daysafter surgery
RT= 7,5RT= 7,6RT= 7,6RT= 7,8

The results show that there are changes in RT before and after surgery, neither in controls nor in the treated animals, thus indicating that the SHA in combination with'gellan used as a biomaterial against adhesions in no way affects the clotting time of blood in the treated animals.

Histological evaluation:

Table 2 shows the evaluation scores obtained for samples treated animals, as described above, in comparison with samples of untreated animals that are negative controls.

SamplesThe average point score, the article is pensato changing in accordance with the formation of fibrous tissueThe average point score, changing stepwise in accordance withthe formation of adhesions in the dura matrix
ControlAssessment 1,5Assessment 2
G/SHAEvaluation of 0.3A score of 0
ADCON-LAssessment for 1.1Evaluation of 1.8

The results clearly show that the biomaterial according to this invention is quite effective to prevent the formation of fibrous tissue, stick to the meningeal dura membrane matrix and compressive her and, consequently, also the nerve roots that protrude forward from the spinal cord.

Anatomical observations:

The figure shows the results obtained from anatomical evaluation, expressed as scoring from 0 to 4, all tested devices against adhesions compared with the same quantities of untreated controls.

As can be clearly seen in the drawing G/SHA and'gellan as such, the new anti-adhesions of the present invention completely prevent the formation of postoperative adhesions in the spine, giving much better results than the device ADCON-L,which is usually used in clinical practice due to its proven effectiveness.

Finally, the above graph shows that SA as is not equivalent to semi-synthetic sulfated polymer, such as SMS-S and cannot be replaced by such equivalent. In fact, its combination with the'gellan (G/CMC-S) undoubtedly gives a negative result, especially when compared with the result obtained with gel-G/SHA.

As described thus of the invention it is clear that the examples of the preparation of the biomaterial, which is the subject of the invention can be modified in various ways. Such modifications should not be considered as deviation from the essence and objectives of the invention, and all such modifications which will be obvious to the expert in this field, does not go beyond the limits of the following claims.

1. Biomaterials consisting of deacetylating'gellan, to prevent postoperative adhesions.

2. The biomaterials according to claim 1, where postoperative adhesions are a postoperative adhesions in the spine.

3. The biomaterials according to claim 2, in which deacetylating'gellan a combination of sulfated hyaluronic acid or its sulfated derivative, to prevent postoperative adhesions.

4. The biomaterials according to claim 3, in which the sulfated hyaluronic acid or its sulfated derivative has come a degree of sulfate crystallization from 0.5 to 3.5.

5. The biomaterials according to claim 4, in which the sulfated hyaluronic acid or its sulfated derivative has a degree of sulfate crystallization, is equal to 3.

6. The biomaterials according to claim 5, in which the sulfated hyaluronic acid or its sulfated derivative has a molecular weight of from 10,000 to 1×106Yes, and preferably from 100000 to 250000 Yes.

7. Biomaterials according to any one of claims 1 to 6 in combination with a pharmacologically and/or biologically active substances.

8. Biomaterials according to any one of claims 1 to 6, made in the form of sponges, gels or hydrogels, foams and powders.

9. The biomaterials according to claim 7, made in the form of sponges, gels or hydrogels, foams and powders.

10. Biomaterials according to any one of p-6, in which the mass ratio deacetylating'gellan and sulfated hyaluronic acid or its sulfated derivative is in the range from 1.5:1, 2:1 to 2:1.5, and preferably equal to 2:1.

11. The biomaterials according to claim 7, in which the mass ratio deacetylating'gellan and sulfated hyaluronic acid or its sulfated derivative is in the range from 1.5:1, 2:1 to 2:1.5, and preferably equal to 2:1.

12. The biomaterials according to claim 8, in which the mass ratio deacetylating'gellan and sulfated hyaluronic acid or its sulfated derivative is in the interval for which f 1.5:1, 2:1 to 2:1.5, and preferably equal to 2:1.

13. Biomaterials according to any one of p-6, in which the derivative of hyaluronic acid selected from:
A) of ester by esterification of from 5 to 65%;
B) internal esters with internal esterification of from 1 to 15%;
C) percarboxylic ON with percarboxylic from 1 to 50%.

14. The biomaterials according to claim 7, in which the derivative of hyaluronic acid selected from:
A) of ester by esterification of from 5 to 65%;
B) internal esters with internal esterification of from 1 to 15%;
C) percarboxylic ON with percarboxylic from 1 to 50%.

15. The biomaterials according to claim 8, in which the derivative of hyaluronic acid selected from:
A) of ester by esterification of from 5 to 65%;
B) internal esters with internal esterification of from 1 to 15%;
C) percarboxylic ON with interest percarboxylic from 1 to 50%.

16. Pharmaceutical compositions containing biomaterials according to any one of the preceding paragraphs, in combination with a filler and/or pharmacologically acceptable excipients.



 

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FIELD: medicine.

SUBSTANCE: invention refers to medicine and can be used for post cosmetic surgery rehabilitation that is ensured by introduction of mixed medicinal preparations in lymphoid region of orbit, namely within pterygopalatine fossa and parotid. The mixed preparations introduced in pterygopalatine fossa are lidocaine 50-100 mg, dexamethasone 4-8 mg, glucose 400-800 mg, dalargin 1-2 mg and Lydasa 16-32 UN. And parotid injection contains lidocaine 50-100 mg, aminophylline 24-28 mg, hystochrom 10-20 mg and Lydasa 16-32 UN. Introduction of the mixed preparations is carried out on right or left side of face alternately every 4-5 hours daily within the course 6-8 procedures. Then 3-5 procedures of discrete plasmapheresis follow with using no more than 20-25% of total blood volume for exfusion. The prepared cell mass is incubated with 250-350 cm3 of ozone-oxygen mixture of ozone concentration 3000-3200 mkg/l.

EFFECT: method allows reducing post cosmetic surgery rehabilitation time owing to stimulation of regional lymph flow ensured by high local concentration of medical preparations.

2 ex

FIELD: medicine; surgery.

SUBSTANCE: mini thoracotomic access with the subsequent aspiration of a transudate for treatment of patients with secondary recurring transudate pleuritis is made in the 6th intercostal space. Then pleurodesis is carried out under visual control, treating thus parietal and visceral leaves of a pleura by the drape moistened plentifully with the 70% ethyl alcohol solution. After that active drainages are placed in a pleural cavity and an operational wound is taken in.

EFFECT: full and proof obliteration of a pleural cavity, prevention of local liquid accumulations relapse occurrence in it at the expense of uniform total processing of a pleural cavity by an ethyl alcohol solution under visual control.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and can be used for prevention and/or treatment of visceral and parietal peritoneum adhesions. It is ensured as follows. At the final stage of operation, 1-4 silicone male drainage tubes of internal diametre 4-8 mm are inserted in subhepatic space, and/or in left subphrenic space, and/or in right lateral sinus and/or in left lateral sinus. Besides, 1 to 3 silicone female drainage tubes of internal diametre 6-8 mm are installed in left and/or right lateral canals, and/or in small pelvis cavity. Provided the blood analysis showed lymphocyte content more than 19%, leukocytes at least 3.5×109/l and thrombocytes at least 180×109/l, in early postoperative period, epidural anaesthesia aided 5% glucose, dialysis or Ringer-Lock based solution containing 5-Fluorouracil 0.25-0.75 g/m2 of body surface in amount 800 - 2000 ml is introduced through the inserted male tubes. Solution exposition in abdominal cavity makes 4-23 hours. After that the solution is evacuated from abdominal cavity through the drainage tubes. Further all drainage tubes are removed. The procedure is carried out daily starting from the first to fifth days after operation.

EFFECT: method allows for high effectiveness of prevention and/or treatment of postoperative adhesions in abdominal cavity including recurrent adhesions owing to application of complex of the preparations that effect adhesive process in abdominal cavity without disturbing intestinal transit.

3 cl, 4 ex

FIELD: medicine.

SUBSTANCE: treatment of the patients with purulent wounds is ensured by bathing of a purulent wound that is being in alterative and exudative inflammation phase, with physiologic saline. It is followed with registering fluorescence of the purulent wound within its depth, centre and infiltrate. Thereafter a factor K1=Iav/If is calculated, where Iav is an average fluorescence index of the wound within depth, centre and infiltrate, If is a standard fluorescing reference of a comparison object which is the fluorescence of earlap. Then the wound is sponged with a probiotic in amount 5.0-50.0 ml and more considering the wound extent. It is drained and loosely filled with a probiotic-saturated tampon. Thereafter an aseptic dressing is applied, and conventional integrated therapy is administered. Probiotic re-management of the wound is carried out once a day and more often, with multiple bathing of the purulent wound and fluorescence registration. Provided K1>>K2, where K2 is the fluorescence measured again in combination with the integrated therapy, the same is continued. Otherwise, the integrated therapy is corrected by changing an antibacterial preparation and/or prescribing the other antibacterial preparations and/or additional oral introduction of probiotic Euflorin L and B dosed 1 tablespoon 1-3 times a day. The therapy is prolonged until granulations are observed in the wound, and until K1>>Kn is provided, where Kn is a value verging towards fluorescence powers specific for intact tissues or varies no more than by 5-20%.

EFFECT: higher effectiveness of purulent wounds repair combined with integrated therapy without local application of antibacterial preparations owing to local introduction of probiotics in this case acting as antagonists to pyogenous flora of the wound.

2 tbl

FIELD: medicine.

SUBSTANCE: method involves drying injured zone after having removed dental deposit and additional treating cement surface in inflammation zone with citric acid solution of 0.1 mMole/l concentration during 5 min, and then with 0.06% Chlorohexidine solution and Nikiforov mixture. Sulfacrylate is placed into periodontium pocket as glue periodontial bandage and the lesion focus is treated with ultrasound of 26.5 kHz during 3 s.

EFFECT: accelerated treatment course; activated reparative processes in periodontium; improved mechanical strength; accelerated polymerization in glue bandage.

2 tbl

The invention relates to medicine, in particular to the gynecologist, and can be used to treat ovarian cysts

The invention relates to a method of preventing unwanted pregnancy in an individual, comprising intravaginal administration to the individual an effective amount of a composition containing narrow or monodisperse condensation polymer of aromatic sulfonic acids and aldehyde or its pharmaceutically acceptable salt, as well as to a method of preventing unwanted pregnancy in an individual, including vaginal introduction of the gel containing the above-described condensation polymer

The invention relates to the field of medicine and biology and relates to drugs that regulate metabolism

The invention relates to the field of medicine and AIDS, normalizes metabolic processes in the cell

The invention relates to medicine and veterinary medicine, particularly to pharmacology

The invention relates to biology and medicine and relates to remedies for pneumonia

The invention relates to biology and medicine and relates to means against radiation damage

Drug against shock // 2108790
The invention relates to biology and medicine and relates to a medicinal product that protects from shock

FIELD: medicine.

SUBSTANCE: combined chondroprotective pharmaceutical composition is made in the form of gel and contains chondroitin sodium sulphate, glucosamine sulphate sodium chloride, propylene glycol, Carbomer (Carbopol), lavender oil, methyl parahydroxybenzoate (Nipagin, methylparaben), sodium methabisulphite, ethanol and purified water in the relevant ratio of the components.

EFFECT: stimulated mechanisms of cartilage reparation, suppressed activity of enzymes destroying cartilage tissue, anaesthetising and antiinflammatory action within an application area.

1 ex

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