New active substance for regenerative process and use thereof
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is a group of inventions which refers to medicine, namely dermatology. The group of inventions involves the use of a known compound as an agent for preparing a composition for stimulating and/or accelerating fibroblast proliferation in vivo and ex vivo, and respectively wound healing, as a wound healing dressing containing such compound. This compound represents a copolymer of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propane sulfonic acid salt and propenoic acid 2-hydroxyethyl ester. It may be used either separately or in a combination with the other active substances for inducing or accelerating wound healing. This compound either separately, or in a combination with the other active substance may be introduced on the wound directly and a surrounding area or mucous membranes by local application. The presents inventions also find application for making dressings on the basis of hydrogels and hydrocolloids which contain said copolymer. For the purpose of the use in vivo, the given copolymer is used in the composition or in the dressing for wound healing that promotes better improvement of wound surface regeneration and healing stimulation.
EFFECT: use of the copolymer ex vivo is effective for autologous skin or skin-epidermal transplants as that enables accelerating fibroblast proliferation.
The object of the invention is essentially a new application connection, which is a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ether.
More specifically, the present invention relates to the use of this compound as an agent to stimulate and/or accelerate the proliferation and/or differentiation of fibroblasts, in particular for the manufacture of a composition intended to stimulate healing or alternative for the manufacture of a composition intended for use ex vivo to generate cells for skin grafts.
The invention also relates to a bandage for the treatment of wounds containing this compound, alone or in combination with other active ingredients.
It is known that open wounds, including burns, ulcers, neuropathic ulcers, venous or arterial ulcers, diabetic ulcers, decubitus ulcers, bullous lesions, exudative wounds, superficial dermal-epidermal damage, which can be chronic or acute, the vast majority of wounds.
One of the primary goals in the treatment of wounds, regardless of its nature or origin, is the closure of this wound.
In addition, it is known that wound healing is a natural biological phenomenon is s, where human and animal tissue is able to repair localized damage through the process of repair and regeneration, which are specific to it.
In General, wound healing occurs in three phases: phase purification, the phase of granulation and epithelialization phase, where each of these three phases is characterized by specific cellular activities that cause the progression of the process of reparation in accordance with the exact chronological sequence.
Phase purification is characterized by the appearance of early inflammatory events. Immediately after injury begin secretion, originating from blood and lymphatic vessels. Coagulation induced activation of thrombokinase, which is released when it is accompanied by the formation of fibrin. After about 10 minutes starts exudation, which should provide protection against infection and cleansing wounds. About 4 days later, the damage comes in the proliferative phase. The body begins to compensate for the loss of the substance of the new cloth. For this purpose fibroblasts initially produce mucopolysaccharides, which serve as a matrix for the development of collagen fibers of the connective tissue. Between 6-th and 10-th day, on average, starts phase of differentiation. Begins the maturation of collagen fibers. The wound is reduced the od of the influence of special cells, myofibroblasts. Granulation tissue is gradually becoming depleted water and contains fewer vessels, thus becoming stronger. Then it is converted into scar tissue, which, in turn, stimulate the contraction of the scar.
During the second phase of healing, known as the phase of granulation tissue, fibroblasts play an important role. The granulation phase lasts about 3 weeks, and during the normal healing process takes place epithelialization phase. Fibroblasts proliferate in the wound, as well as precursor cells keratinocytes from the wound edges, from hair follicles and sweat glands. After 3 days, fibroblasts produce collagen fibers which are oriented in accordance with the forces to which they are exposed. Their proliferation is controlled by a set of defined factors. As a General rule, this proliferation is stopped when the granulation tissue made up for the loss of substance, and when the proliferation of fibroblasts reached the level of the edges.
The fibroblast is one of the main agents in the healing process. Indeed, about 6 days more than half of fibroblasts present in the wound, converted to myofibroblast. These cells are characterized by the presence in their cytoplasm of the contractile myofibrils, which cause the reduction of the wound and, therefore, slimming the surface area of the wound and accelerate its closing.
These cells, therefore, play an indispensable role in reducing wound, which is the main phenomenon of spontaneous closure in abdominal wound. More than 40% of myofibroblasts (containing contractile protein, smooth muscle actin alpha) are present in the granulation tissue. When the wound heals, these cells die, although the signal that triggers their disappearance, is not fully understood.
The fibroblast is also a key cell proliferative phase. The secretes fibroblast collagen type III, and then the collagen type I and heparan sulfate, which are fundamental components of the dermal extracellular matrix, but also hyaluronic acid, chondroitin sulfate, fibronectin and collagenase, leading through the result to the closure of the wound.
The healing process, even for small wounds or holes, can last for several hours, several days or several weeks or even more in some circumstances, as, for example, in the case of ulceration, where the wound can be kept for much longer periods of time, i.e. months or years.
During this period of healing, if he lasts a short or long time, the wound may be susceptible to infestations of any type (pathogenic organisms or foreign substances) up until regen is the situation of new tissue will not completely close the hole.
To prevent any infection of the wound is usually treated to remove any contaminants (dust, debris, etc.), capable of introduction of pathogenic substances in the area of the damaged region. Consistently conducts the removal of dead tissue in this area and disinfection. In some cases, introducing a certain number of stitches to facilitate wound closure. Once these stages are carried out, the wound support in an environment conducive to healing. To do this, use different types of bandages to prevent the introduction of pathogens and/or their proliferation.
Therefore, in the treatment of wounds, it is important to stimulate the phenomenon of wound closure to prevent, for example, invasion of the wound microorganisms or foreign substances and, consequently, infection of the wound. The need to have funds for the induction or stimulation of the wound-healing process.
For the purpose of inducing or accelerating the healing of wounds you can enter a number of active agents. These active agents may act at different levels and in different phases of healing. They vary according to the stage and type of wound to be treated. These active agents may, for example, be a factor in the growth of fibroblasts and/or keratinocytes (such as the main factor in growing the and fibroblasts) or pseudovector growth (such as mannose-6-phosphate), glycosaminoglycans (such as hyaluronic acid, collagen and so on), hormones such as estradiol, dehydroepiandrosterone, and so on), polysaccharides (such as dextran), etc.
It was discovered, unexpectedly and surprisingly, it is also possible to stimulate and/or accelerate the proliferation and/or differentiation of fibroblasts and, therefore, stimulate healing through connection, which is a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ether.
Preferably the above-mentioned salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.
This copolymer is a product which is in itself known, in particular, in the field of cosmetics due to its emulsifying/stabilizing properties and good thickening ability.
Such a product, for example, sold by SEPPIC under the trade name Sepinov EMT 10®.
Thus, in accordance with the first aspect, the object of the present invention is the use of a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ester for the manufacture of a composition intended to stimulate and/or accelerate the proliferation of fibroblasts in vivo or ex vivo, and in which lastnosti, for the manufacture of a composition intended to stimulate healing.
The above-mentioned copolymer can be applied in vivo or ex vivo.
As an example of the application of ex vivo may be mentioned the use of this compound for the preparation of culture medium for stimulating the proliferation of fibroblasts. It turns out that this application is useful for autologous skin grafts or skin epidermal layer. This is because with this type of transplant techniques of cell culture used in order to obtain a sufficient surface area of the skin from a small sample taken from the patient or the patient. The use of a copolymer according to the present invention makes it possible to accelerate the proliferation of fibroblasts and, therefore, it appears that it is useful for this type of treatment.
In the context of its application in vivo the above-mentioned copolymer can be applied for the manufacture of a composition, which will enable its direct application to the wound and surrounding area, or even on the mucous membrane, preferably by topical application. Preferably the copolymer include in a bandage.
Typically, the above-mentioned copolymer can be used alone or in combination with other active substances, which provide the ability to induce or is Smriti healing, or which may play a favorable role in the treatment of wounds, such as, for example, antimicrobial agents, or pain relievers. This combination of active agents provides the combined conservative treatment of wounds. Among the active substances that can be applied in the context of the invention, one can mention, as examples, bactericidal or bacteriostatic agents (bleach, chlorhexidine, of silver salts, zinc salts, metronidazole, neomycin etc), agents for stimulating healing (hormones, peptides etc), enzymes to stimulate cleansing of the wound (pepsin, trypsin, and so on), protease inhibitors or metalloproteinase, pain relievers or local anesthetics (lidocaine, cinchocaine) or nonsteroidal anti-inflammatory drugs (ibuprofen, Ketoprofen, fenoprofen, diclofenac).
Preferably the above-mentioned copolymer should be used in combination with the sulfated saccharide or a salt or complex of sulfated saccharide. This sulfated saccharide may, for example, be octasulphate sucrose in the form of a complex or salt with a metal such as Na, K, Ca, SB, Ba, Al, Zn, si, Zr, Ti, Mn, or Os, or with an organic base, such as an amino acid. In particular, preferred results are obtained when the above-mentioned copolymer is used in combination potassium octasulphate sucrose, which is an active ingredient known for its action in the healing process.
Studies of cell proliferation in vitro unexpectedly given the opportunity to show that the copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ester exhibits activity on the proliferation of fibroblasts at a very low dose. Specifically, this activity see, when the copolymer is present in the culture medium at a concentration of 0,00064 mg/ml
Also it is shown that, particularly preferably, the above-mentioned copolymer is also active in several days. Tests conducted in vivo, given the opportunity to detect activity on the proliferation of fibroblasts in 72 hours after the inclusion of the specified copolymer in the culture medium. Particularly preferably, when the copolymer include in a bandage. Specifically, the same bandage can be applied for several days, and at the same time it remains active without the need for its replacement.
Typically, the copolymer used in the context of the present invention may be included in any type of composition, such as, in particular a solution, cream, gel, mass (sludge), in particular elastomeric mass, or bandage. The copolymer may be included in the compress. The term "compress" as meaning any type AB is orbimage material, usually used in dressings, such as, for example, textile materials, which may be an absorbent nonwoven materials (e.g., based on viscose), possibly combined with non-absorbent non-woven materials (such as polyester). It may also include overabsorbed fiber (such as Lanseal® Fibres, commercially available from Toyobo company, Ltd) or polyurethane foam.
In particular, the copolymer may be present in the mass, part of the dressing, or on a separate layer dressings, or as an alternative, the coating covering the surface of the bandage, designed to bring it into contact with the wound for its treatment.
The term "bandage" is here meant to include any type of well-known bands, and preferably the edge of the dressing. These dressings are commercially available, e.g. under the trade names Tulle Gras®(Solvay Pharma), Physiotulle®(Coloplast) or even Urgotul®(Laboratoires Urgo) and described in the patent EP 1143895.
These border dressings, as a rule, are in the form of a sieve or mesh, covered with a mass, usually elastomeric mass. They may also consist of masses without fabric or mesh-shaped layer, which may or may not have through holes depending on the type of wound that dressings (layer, which has through holes, etc is doctitle use on exudative wound, when the mixture has or has weak absorbent ability, holes, thus, enable the evacuation of exudate from the wound).
The present invention also finds application for the manufacture of bandages, based on hydrogels and hydrocolloids, which include the above-mentioned copolymer. Known dressings based on hydrocolloids are commercially available, for example, under the names Algoplaque®(Laboratoires Urgo), Duoderm®(Convatec) and Comfeel®(Coloplast). Such dressings are described in the following patent applications: FR 2392076, FR 2495473 and WO 98/10801 and EP 264299.
The copolymer used in the context of the present invention can be incorporated into the absorbent element, such as a wrap or foam, for example, by depositing it on the surface intended to bring into contact with the wound, as described in patent application WO 2006/007844.
The present invention also finds application for the manufacture of edge dressing in combination with an absorbent layer, such as foam or wrap, or hydrocolloid in combination with absorbent foam. Such dressings are known and are commercially available, e.g. under the trade names UrgotulDuo®and Cellosorb®(Laboratoires Urgo). In such bands the above-mentioned copolymer may be included in the mass and/or the absorbent layer.
Edge dressing, preferably use is Jaimie in the context of the present invention, consist of elastomeric mass, i.e. consisting of one or more than one elastomer selected from block copolymers of styrene-olefin-Sterol, and one or more than one compounds selected from plasticizers, adhesive resins, and optionally antioxidants.
Such elastomeric mass is well known to specialists in the art and described, for example, in the book "Advances in Pressure Sensitive Adhesive Technology", published by Donatas Satas in April 1995 Chapter 7, "Wound dressings", s-171.
When it is incorporated into the dressing, such as the edge of the bandage, the above-mentioned copolymer can be applied at a concentration of from 1% to 5 wt.% relative to the mass of the elastomeric mass. It is shown that this concentration is sufficient to activate fibroblasts and, therefore, to stimulate healing.
Typically, the above-mentioned copolymer should be present in the bandage in number, which can range between 0.1% and 20 wt.% regarding the mass, in which it is included, and preferably between 1% and 5 wt.%.
According to the second aspect of the present invention is coated dressings described above, which includes a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ether.
To demonstrate the activity of the above-mentioned copolymer in fibroblasts was Prov who were in vitro study, using two types of experiments:
1. Copolymer, alone or in combination with the active substance (in this case potassium sucrose by octasulphate) was added directly to the culture medium of fibroblasts at various concentrations.
In this case, the various cultivation of the copolymer, of one or in combination with potassium sucrose by octasulphate thus prepared was added to the culture medium.
Breeding copolymer Sepinov EMT 10 at 0.011 mg/ml and potassium sucrose octasulphate when 0,00064 mg/ml, therefore, tested in culture medium containing fibroblasts.
2. Copolymer, alone or in combination with the active substance (in this case potassium sucrose by octasulphate) included in the matrix edge of the bandage, and then the bandage was applied to the culture wells containing fibroblasts.
In this case, the various border dressings containing copolymer at various concentrations, in combination or not in combination with potassium sucrose by octasulphate were made in accordance with the method described below. Edge dressing that does not contain neither of these two active agents, was also fabricated and tested for comparison.
A method of manufacturing a test bandages
a. Getting elastomeric masses
Various elastomeric mass (examples 1-5) were prepared with the use of the eat to the following components in mass, specified in table 1:
- Elastomer: block copolymers of poly(styrene-ethylene-butylene-styrene) (abbreviated SEBS); Kraton G 1654 and G 1651, commercially available from the company Kraton;
- Plasticizer: mineral oil: Ondina 917, commercially available from Shell company;
- Antioxidant: Irganox 1010, commercially available from the company Ciba Specialty Chemicals;
- A fatty substance: petroleum jelly: petroleum jelly Codex A, commercially available from the company'aiglon;
- Hydrocolloid: sodium carboxymethyl cellulose: CMC Blanose 7H4XF, commercially available from the company Hercules;
- Additional active ingredient: potassium sucrose octasulphate: commercially available from the company Euticals;
The copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylamide ether propanolol acid: Sepinov EMT 10, commercially available from the company SEPPIC.
Mass-based elastomer was prepared by mixing in a Z-blade mixer at set point temperature 155°C:
1. Triple elastomers styrene-ethylenebutylene-styrene mixed with half mineral oil and an antioxidant.
2. After 30 minutes, to the mixture with petroleum jelly.
3. After 40 minutes add the rest is mineral oil.
4. After 55 minutes, to the mixture of the sodium carboxymethyl cellulose, where suitable, the active agent (agents).
The mixer is empty after 70 minutes.
B. The manufacture of bandages
the Edge of the bandage, consisting of a bolt, covered elastomeric mass, were prepared using the above-mentioned elastomeric mass.
More specifically, they used a sieve formed from yarns thermosetting Voile made of polyester (polyethylene terephthalate) 33 decitex in the directions of warp and weft, with the square mesh sieve with an aperture of about 0.8 to 1 mm2(mesh 555, commercially available from the firm MDB Texinov).
This sieve covered with a layer of molten elastomeric mass at 135-145°C, and then the excess was removed by passing between two fixed rollers having a gap between them 200 μm. Thus obtained strip was cut, and then formed a complex with protective polyester film having a thickness of 23 μm, on each of its sides, forming, thus, individual bandages are Packed in impermeable protective bags and sterilized with β-radiation at 25 kGy.
|Components||Example 1||Example 2||Example 3||Example 4||Example 5|
|Mineral oil (Ondina 917)||75||74||70||62,38||69,9|
|S-EB-S (Kraton G 1651)||a 4.9||a 4.9||a 4.9|
|S-EB-S (Kraton G 1654||6||6|
|Antioxidant (Irganox 1010)||0,1||0,1||0,1||0,12||0,1|
|(petroleum jelly Codex A)|
|(CMC Blanose 7H4XF)|
|Sepinov EMT 10||1||5||5||5|
|Potassium sucrose octasulphate||7,5|
The effect of copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ether on the proliferation of fibroblasts was determined in accordance with the following Protocol.
Demonstration of the activity of the above-mentioned copolymer on the proliferation of fibroblasts
Type: pool normal fibroblasts of human skin (NHDF) R9PF2
Culture: 37°C, 5% CO2
DMEM (modified Dulbecco Wednesday Needle, Invitrogen 21969035)
2 mm L-glutamine (Invitrogen 25030024)
50 u/ml penicillin (Invitrogen 15070063)
10% fetal calf serum (V/V, Invitrogen 10270098).
Tested headbands with the size of the hole made, as described previously, using an elastomeric mass of examples 1-5, and the cultivation of a copolymer Sepinov EMT 1 to 0.011 mg/ml and potassium sucrose octasulphate to 0,00064 mg/ml
Effects on proliferation:
Fibroblasts were sown in 12-hole tablets at low density (60% confluentus), and then cells were treated with dilutions or pieces of bandages were applied to these plates and held in place by means of tubes (called "test"). Control without a bandage, without dilution, but with tube (called "control").
Then cells were incubated for 24 hours, 48 hours and 72 hours. For each incubation period was added tretirovanie thymidine ([methyl-3H]-thymidine, Amersham TRK 686, final concentration of 2.5 MCI/ml) in the past 24 incubations, and then the DNA of cells from the cell layers were extracted and purified, and the radioactivity incorporated into DNA was considered, using a scintillation counter.
The results are expressed in counts per minute (CPM), then as percentage relative to control in accordance with the following formula:
cpmtest: number of pulses per minute, obtained for the test
cpmcontrol: number of pulses per minute obtained for the control
All experiments were performed three repetitions.
The results are shown below in tables 2-4.
|The results of the study of NHDF proliferation after activation titiraupenga thymidine 24 hours|
|Dressing in accordance with example 1||130|
|Dressing in accordance with example 2||196|
|The results of the study of NHDF proliferation after activation titiraupenga thymidine after 48 hours|
|Dressing in accordance with example 1||181|
|Dressing in accordance with example 2||260|
|Dressing in accordance with example 3||506|
|Dressing in accordance with example 4||456|
|Dressing in accordance with example 5||243|
|Potassium sucrose octasulphate at 0.011 mg/ml||106|
|Sepinov EMT 10 when 0,00064 mg/ml||125|
|Potassium sucrose octasulphate at 0.011 mg/ml and Sepinov EMT 10 when 0,00064 mg/ml||152|
|The results of the study of NHDF proliferation after activation titiraupenga thymidine after 72 hours|
|Dressing in accordance with example 1||150|
|Dressing in accordance with example 2||120|
|Dressing in accordance with example 3||493|
|Dressing in accordance with example 4||292|
|Sepinov EMT 10 when 0,00064 mg/ml||147|
Thus, these in vitro experiments was given the opportunity to demonstrate the role of copolymer Sepinov EMT 10 when Strait is perezii fibroblasts, as well as the combined activity of this copolymer and potassium sucrose octasulphate on the same cells.
The effect is particularly favorable when the copolymer Sepinov EMT 10 include elastomeric mass concentration of 5% of the total mass, where this effect takes place after 48 h and 72 h of contact with the cell culture environment.
The copolymer used separately when diluted in cell culture medium at very low concentrations (0,00064 mg/ml)significantly stimulated the proliferation of fibroblasts.
It was also possible to observe that surprising that when the copolymer Sepinov EMT 10 is used in combination with potassium sucrose by octasulphate, there is a synergistic effect on the proliferation of fibroblasts. This synergy was observed, in particular, when potassium sucrose octasulphate added to the culture medium at a concentration of 0.011 mg/ml, and the copolymer Sepinov EMT 10 at a concentration of 0,00064 mg/ml
The copolymer used in accordance with the present invention, therefore, is particularly preferred for the treatment of wounds and, in particular, to stimulate healing, especially when it is turned on in the dressing.
1. The use of a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ester for the manufacture of a composition intended to stimulate and/or accelerate p is oliveraie fibroblasts in vivo or ex vivo.
2. The use according to claim 1 for the manufacture of a composition intended to stimulate healing.
3. The use according to claim 1, characterized in that the said copolymer is combined with one or more than one active substance.
4. The use according to claim 1, characterized in that the said copolymer is combined with the sulfated saccharide, preferably potassium sucrose by octasulphate.
5. The use according to any one of claims 1 to 4, characterized in that the salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.
6. The use according to claim 2, characterized in that the said copolymer is combined with one or more than one active substance.
7. The use according to claim 2, characterized in that the said copolymer is combined with the sulfated saccharide, preferably potassium sucrose by octasulphate.
8. The use according to claim 6 or 7, characterized in that the salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.
9. Bandage for treating a wound, characterized in that it contains a copolymer salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and 2-hydroxyethylphosphonate ether.
10. The bandage according to claim 9, in which the above-mentioned copolymer is combined with one or more than one active substance.
12. The bandage according to claim 9, in which the specified copolymer is present in an absorbent element comprising a bandage.
13. The bandage according to claim 9, in which the specified copolymer is present in the mass, preferably elastomeric mass, component specified bandage.
14. Bandage according to item 13, in which the specified copolymer is present in amounts of between 0.1% and 20 wt.%, and preferably between 1% and 5 wt.% in relation to the weight of the mass, in which it is included.
15. Bandage according to any one of p-14, in which the salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.
16. The bandage according to claim 11, in which the specified copolymer is present in an absorbent element comprising a bandage.
17. The bandage according to claim 11, in which the specified copolymer is present in the mass, preferably elastomeric mass, component specified bandage.
18. The bandage on 17, in which the specified copolymer is present in amounts of between 0.1% and 20 wt.%, and preferably between 1% and 5 wt.% in relation to the weight of the mass, in which it is included.
19. Bandage according to any one of § § 11, 16-18, in which the salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.
SUBSTANCE: invention refers to medicine, namely medical education, and may be used for blood grouping with the use of mixtures imitating whole blood and diagnostic serums for student training of ABO-based blood grouping technique. For this purpose, the mixtures imitating whole blood and diagnostic serums are presented by cow milk and raw albumen dissolved in water and painted to blood colour with 2.5-3% direct scarlet solution and imitators of isohemagglutinating serums with using water and 2% sulphosalicylic acid.
EFFECT: method provides 100% accuracy of blood grouping, enables multiple and unassisted technique with ensured safety, ease, low price for assimilation and check of ABO-based human blood grouping skills on laboratory classes in medical institutions and schools.
4 ex, 4 tbl
SUBSTANCE: invention refers to medicine, namely restorative medicine and angiology, and may be used for treating the patients with chronic lymphovenous insufficiency of lower extremities. That is ensured by applying a homogenised gel of brown algae at temperature 28-30°C and wrapping the extremities with non-woven tissues (drapes). That is followed by immediate alternative pneumatic compression by the Lympha-E apparatus on the lower extremities. That involves the ascending wave pressure memorising mode, the II operation mode at pressure 60-90 mm Hg for 40-60 minutes. The procedures are daily, 5 times a week with a pause of 2 days. The therapeutic course is 10-20 procedures.
EFFECT: method provides higher clinical effectiveness at all the stages in any length of the disease including due to additional stimulation of the lymphodrainage function, improved microcirculation, peripheral haemodynamics, improved plasma-coagulation phase of haemostasis, improved tissue trophism.
SUBSTANCE: simulating osteoarthrosis of a temporomandibular joint is ensured by using the antithyroid preparation mercazolil (thiamazole) in the form of a water-starch suspension The preparation is introduced orally through a probe in dose 10.0-15.0 mg/kg of rat's body weight once a day. The preparation is introduced daily during 90 days.
EFFECT: method provides creating an optimal model of no-inflammation degenerative-dystrophic joint injury and enables practicing methods for studying, preventing, treating this disease.
1 tbl, 2 ex, 2 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of invention refers to medicine, and concerns treating nonsense mutation(s) associated diseases: Duchene muscular dystrophy and cystic fibrosis. What is presented is the use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid or its pharmaceutically acceptable salts, solvate or hydrate in preparing a drug for treating Duchene muscular dystrophy associated with nonsense mutation in position 1417, 3625 or 492 of dystrophin; and cystic fibrosis associated with nonsense mutation in position 414, 493, 1316, 553, 542, 1162, 122, 1455, 822, 60, 764, 1291, 849, 434, 88, 1158 or 6542 CTFR. What is also presented is the use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid or its pharmaceutically acceptable salts, solvate or hydrate in preparing a drug for producing a functional readthrough protein in a subject having Duchene muscular dystrophy and cystic fibrosis.
EFFECT: use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid provides suppression of premature termination of translation in a subject by mediating nonsense codon reading and producing the functional protein in the amount sufficient for treating the disease.
3 cl, 3 dwg, 17 tbl, 16 ex
SUBSTANCE: invention relates to medicine, namely to pediatrics, in particular to physical training of 7-10 years old children in school conditions. For this purpose during lesson of physical training exercises are performed in conditions of saturation of gymnasium with sea water aerosol. Selection of physical exercises is performed depending of season. In autumn season period exercises developing endurance, constitute 30-40% from total number of exercises. In winter period exercises developing speed-force abilities constitute not less than 30% of total number; exercises, developing flexibility constitute not less than 20%; exercises developing coordination abilities constitute not less than 30%. In spring period exercises developing speed abilities correspond 30-40% of total number of exercises. Saturation of gymnasium with sea water aerosol is performed in two stages. First stage is carried out at the end of autumn and beginning of winter period in course of final part of each lesson, 4 minutes long, increasing this time after each four lessons by 2 minutes until 8-10 minutes duration is achieved. Second stage is carried out at the end of winter period and beginning of spring period in the course of main part of lesson with 10 minutes duration, gradually increasing this time after each four lessons by 5 minutes until 5-35 minutes duration 2 is achieved. Saturation of gymnasium with sea water aerosol is realised during 15-17 days in each period. Multivitamin complex is additionally introduced at the end of the lesson after saturation of gymnasium with sea water aerosol.
EFFECT: method ensures essential improvement of state of health of children of primary school age, prevention of diseases of upper airways, improvement of parameters of physical fitness and functional parameters of main systems of organism.
6 cl, 4 dwg, 6 tbl, 2 ex
SUBSTANCE: what is presented is an antibody characterised by the fact that it binds the human p40 IL-12 subunit and comprises six CDR regions (CDR1, CDR2, CDR3 from the light chain and CDR1, CDR2, CDR3 from heavy chain). There are described: an antibody construct, an antibody conjugate, versions of coding nucleic acid, versions of vectors (for expression and replication), versions of a host cell, a method for producing the antibody, versions of compositions, versions of a method of treating an individual having unfavourable IL-12 activity, a method of reducing IL-12 activity in a human.
EFFECT: use of the invention can find application in medicine for prevention and treatment of acute and chronic diseases associated with activity of the human p40 subunit.
115 cl, 24 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biology and medicine, and concerns a lifespan increasing drug.
EFFECT: substance of the invention involves the use of hyaluronidase immobilised by electron-beam synthesis nanotechnology as a drug for retardation of natural aging and lifespan increase.
1 ex, 3 tbl
SUBSTANCE: what is offered is application of 2-ethyl-6-methyl-3-oxypiridinium L-asparaginate as a drug possessing actoprotective, antihypoxic, neuroprotectivem antiamnestic and thermoprotective activity. It is shown that actoprotective activity of this chemical compound 1 mg/kg exceeds that of the nearest analogue of the declared drug - Mexidol 5 and 10 mg/kg. Thermoprotective activity of this substance 5 mg/kg twice exceeds that of the nearest analogue of the declared drug - Mexidol 50 and 100 mg/kg. Antihypoxic, neuroprotective and antiamnestic activities of the declared drug in animals of various models exceed and/or are highly competitive with the nearest analogue Mexidol and the other reference preparations.
EFFECT: drug is used for the purpose of higher usual and extreme physical performance, as well as for treating acute and chronic disturbed cerebral circulation, including ischemic stroke and other conditions and diseases accompanied by depression of cognitive functions and neurodegeneration, including in ageing.
SUBSTANCE: invention refers to a composition for cell, tissue and organ preservation containing as an active ingredient indole and indazole compounds of formula (1), or their pharmaceutically acceptable salts or isomers which are effective for prevention of the damage of organs, recovered cell systems or tissues caused by low-temperature storage, transplantation surgery or post-transplantation reperfusion.
EFFECT: invention also refers to a method for preparing said composition.
21 cl, 5 dwg, 6 tbl, 156 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, particularly to a radioprotective agent. Fresh, dry or frozen wild leek (Allium ursinum) is applied as the radioprotective herbal agent.
EFFECT: agent described above shows effective radioprotective action.
SUBSTANCE: invention refers to medicine, particularly pharmaceutical preparations, namely: plasters for transdermal application. Substance of invention consists in the fact that a transdermal plaster representing a matrix system and comprising a lining layer, a matrix layer and a lightproof protective coating in the following proportions is produced: 6.72 wt % of hypoxene substance, 15.11 wt % of sodium metabisulphite in propylene glycol with 0.067% of sodium metabisulphite, as well as 56.0 wt % of 95% ethanol and 22.17 wt % of PVP K30. The plaster aims at the transdermal introduction of hypoxene. A plaster area is 25 cm2.
EFFECT: offered plaster used for treating and preventing chronic diseases allows avoiding the problems related to oral administration, improves patient compliance, enables prolonged maintenance of the hypoxene concentration; it is suitable for purposes of combination therapy.
6 dwg, 1 tbl
SUBSTANCE: invention refers to high-molecular compounds for medical purposes. Water-soluble polymeric complexes of antiviral agent arbidol of general formula: are described, where: Arb - arbidol: ethyl ester 6-bromo-4-dimethyl-aminometil-1-methyl-5-oxy-2-feniltiometilindolinil-3-carboxylic acid hydrochloride monohydrate; m1=100-(m2+m3) mol %; m2=(7.6-9.8) mol %; m3=(11.5-13.6) mol %; content of Arb=26.4-32.1 wt %.
EFFECT: obtained water-soluble polymeric complexes of arbidol may find application in pharmacology, as they can serve as basis for new effective and safe antiviral drugs and their dosage forms.
1 cl, 6 ex, 4 tbl, 2 dwg
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
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.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention concerns zoopharmacy. A selenium-containing preparation for microelementosis prevention and treatment caused by selenium deficiency in farm animals and poultry contains a stabiliser presented by high-molecular nitrogen-containing polymer 0.1-10.0%, nanosized selenium of null valency 0.0001-1.0%, fat-soluble vitamin E 1.0-20.0%, the molar ratio of vitamin E/selenium 5:1-50:1, a wedding agent 1.0-20.0% and water.
EFFECT: invention provides metabolic process activation and selenium deficiency correction in an animal's body.
3 tbl, 3 ex