RU2259816C1 - Wound-healing remedy - Google Patents

Abstract

FIELD: medicine, cosmetology.

SUBSTANCE: the suggested wound-healing remedy includes a gel-forming agent, an active substance and distilled (deionized) water. As the active substance it contains Mexidol (2-ethyl 6-methyl 3-oxypyrridine succinate) at the following ratio of components, weight%: gel-forming agent 0.5-5.0, stabilizing agent 0.01-0.8, conservant 0.01-1.0, Mexidol 0.01-10.0, distilled (deionized) water - the rest. The suggested remedy is highly efficient. It is of pronounced wound-healing action in 1, 2 and 3 phases of wound process. It quickly liquidates inflammatory processes, decreases painfulness, edema, considerably improves the state of affected tissues, accelerates reparative-degenerative processes and terms of epithelization. It possesses the wide spectrum of action, manifests pronounced action at treating different skin and mucosal lesions - wounds, fissures, bedsores, trophic ulcers of different genesis, surface burns of 1-3 degree, radiation lesions, it, also, removes skin microlesions that possess the nature of cosmetic defects, moreover, it improves skin structure.

EFFECT: higher efficiency of application.

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Description

The invention relates to medicine and cosmetology, in particular to medicines made in the form of a gel for topical application - treatment of injuries of the skin and mucous membrane, trophic ulcers, wounds, burns, injuries of the skin complicated by purulent-inflammatory processes.

A large number of wound healing drugs for topical application are known, made in the form of various dosage forms - ointments, emulsions, applications, gels.

Known ointments used in the first phase of the wound healing process, containing substances that have antimicrobial effects, for example synthomycin, tetracycline, gentomycin and others:

- Kotelnikov V.P. Wounds and their treatment. - M. Knowledge. 1991 .-- 123 s .;

- Kuzin M.I. Wounds and wound infection. - M. Medicine, 1990. - 484 p .;

- Lyapunov N.A., Kalinichenko N.F. New opportunities for local treatment of wounds complicated by anaerobic infection. // Implementation of scientific achievements in practical pharmacy: Thesis. Doc. Rep. Scientific Conf. October 16-18, 1991 - Kharkov, 1991 - 38 p.

The disadvantage of these ointments is the unidirectionality of their action - antimicrobial. They have limitations for use because of their individual intolerance, as well as the danger of developing side effects with prolonged use - reducing the sensitivity of microflora, impaired function of internal organs.

Multicomponent ointments on an osmotically active basis have a complex effect on the wound surface - Levomikol, Sulfamikol, Levosin (Mashkovsky M.D. Medicines: A manual for doctors: in 2 volumes M .: Medicine, 1995, - 575 from.).

However, these ointments also contain antibacterial and sulfamylamide preparations and have side effects.

Known tool for the treatment of various injuries of the skin and mucous membrane "Solcoseryl" containing standardized deproteinized hemodialysate from the blood of calves, which is produced in the form of ointment, cream and gel (Reference Vidal, Medications in Russia, Astra Farm Service, 1997, 531 pp. )

"Solcoseryl" improves metabolic processes, accelerates the regeneration of damaged cells and tissues.

The disadvantage of the drug is its low efficiency. Gel and ointment-based Solcoseryl is recommended for complex use when fresh granulations appear on the surface of a wound, ulcer, or burn surface. This requires long-term treatment and compliance with recommendations, which is often disrupted by patients and does not lead to proper results.

As the closest analogue, the Vitamustine-gel wound healing agent (RU 2185149, class IPC A 61 K 9/06; 31/715; 35/56, A 61 P 29/00, 2002) containing a gel-forming agent, mummy purified and distilled water in the following ratio of components, wt.%:

Gelling agent 1.0-3.0 Mummy peeled 1.0-5.0 Distilled water rest

As a gelling agent in some cases, polysaccharides, at least galactomannan or glucomannan or hyaluronic acid, can be selected. In other cases, gelatin, or pectin, or aerosil, or zeolites can be selected as a gelling agent.

The disadvantages of the above gel composition include the fact that the mummy, as a medicine, is not clinically rigorously studied. It is generally accepted that it is of animal origin. However, all the components that make up its composition have not yet been determined. Therefore, the use of ointment and gel compositions with mummies can cause allergic reactions in patients. As a result, the gel can be used only in a limited number of patients in the treatment of damage to the skin and mucous membranes of various origins. Treatment of patients using this gel requires an individual approach.

The objective of the invention is to provide a highly effective wound healing agent with a more pronounced clinical effect and with wider functionality.

The essence of the invention lies in the fact that the wound healing agent, including a gelling agent, an active substance and distilled water, contains Mexidol (2-ethyl 6-methyl 3-hydroxypyridine succinate) as the active substance in the following ratio, wt.%:

Gelling agent 0.5-5.0 Stabilizer 0.01-0.8 Preservative 0.01-1.0 Mexidol 0.01-10.0

Distilled (deionized) water - the rest.

Using the invention allows to obtain the following technical result.

The proposed wound healing agent is highly effective. It has a pronounced wound healing effect in the 1st, 2nd and 3rd phases of the wound healing process.

Quickly eliminates inflammatory processes. On the 2-3rd day of its use, a decrease in soreness and swelling is noted, the condition of the affected tissues is significantly improved, reparative-degenerative processes are accelerated, and the time for epithelization is significantly accelerated.

It has a wide spectrum of action and functionality, shows a pronounced therapeutic effect in the treatment of various injuries of the skin and mucous membrane - wounds, cracks, bedsores, trophic ulcers of various origins, superficial burns of 1-3 degrees, radiation injuries, eliminates microdamages of the skin, which have the character of cosmetic defects improves skin structure and can be used in medicine and cosmetology.

In this case, the gel has no contraindications, is harmless, does not cause allergic reactions, has no contraindications and age restrictions. It does not require additional use of other drugs, including antibacterial drugs, etc.

The technical result is achieved due to the introduction of the drug Mexidol into the gel, the synergism and prolonged action of its components.

The high therapeutic effect of the gel is primarily due to the wide spectrum of its action and pathogenetic orientation to all links of the wound process.

Mexidol has anti-inflammatory, antibacterial, decongestant, adaptogenic, antihypoxic, antitoxic effects, improves microcirculation, reparative and regenerative processes, increases local immunity, which allows you to simultaneously affect all the links in the pathogenesis of the wound process.

The restoration of microcirculation occurs due to stabilization of the permeability of cell membranes of the walls of capillaries, maintaining their elasticity, and normalizing metabolic processes in them. Mexidol inhibits the intensity of free radical lipid oxidation, as a result of which its direct effect on the respiratory chain increases with an increase in adenosine triphosphate (antihypoxic effect), which leads to an improvement in the supply of oxygen to tissues. Changing the fluidity of the capillary membranes helps to reduce blood viscosity by normalizing the ratio of atherogenic and antiatherogenic functions of lipoproteins, improving the rheological properties of blood, increasing blood supply to tissues, thereby stimulating the processes of regeneration and repair.

The antitoxic effect of Mexidol is achieved by reducing the toxic level of free radicals, the sorption effect on the primary source of inflammatory endotoxemia (binding of endo- and exotoxins), which is enhanced by the presence of sorption properties in the gelling base. This increases the drainage function of the lymphatic system. The gel thus contributes to the rapid removal of toxins from the focus against the background of stabilization of the cell membranes and blood vessels, which provides the active substance, it prevents the penetration of pathogenic microflora, toxins and decay products into the blood.

Mexidol, possessing membrane modulating properties, stimulates detoxification processes, normalizes microflora, which leads to normalization of the metabolism of damaged cells and tissues. By stimulating the energy processes in them, it also contributes to a significant improvement in treatment outcomes.

By stimulating the links of non-specific humoral defense, increasing local immunity due to the phagocytic activity of leukocytes, Mexidol leads to the rapid elimination of the inflammatory process in damaged tissues.

The high therapeutic activity of the gel is also due to the presence of Mexidol, as a powerful antioxidant, at the same time immunomodulating and immunostimulating properties.

Given that Mexidol is a chemically active substance, the authors conducted studies on the selection of a compatible base, since it leads to the destruction of most gelling and ointment bases used in the Russian and foreign pharmaceutical industries.

The following requirements were made to the basis:

- the possibility of application in the pharmaceutical industry

- compatibility with mexidol

- the possibility of use for the mucous membrane

- not to create a barrier for the gradual penetration of the main active substance into the tissues.

As a result of the tests, it was determined that the base is a gelling agent of a series of cellulose ethers, or a gelling agent based on polyvinylpyrrolidone (PVP), or gelling agents based on resins that meet the requirements for their use as a drug medium in the pharmaceutical industry in accordance with regulatory organizations of different countries.

Mexidol in the proposed ratio optimally interacts with the gelling base, giving it its properties, because she is neutral. In this case, the base provides active diffusion and deep penetration of mexidol into damaged tissues, its gradual release and prolonged action, thus allowing to obtain a quick and pronounced therapeutic effect. Moreover, an almost monomolecular film is formed on the surface of the wound, which has high gas permeability with a simultaneous strong biocidal and reparative effect on the tissue.

As a gelling base (gelling agent), hydroxyethyl cellulose or sodium carboxymethyl cellulose or hydroxypropyl cellulose are used:

- hydroxyethyl cellulose for pharmaceutical use (SCE) is a non-ionic cellulose ether that dissolves rapidly in water. In solution, this product acts as a thickener and rheology-controlling agent, as a protective colloid, a binder, a stabilizer and an auxiliary agent for dispersion (the analogue is NATROSOL 250 Pharm).

- sodium carboxymethyl cellulose (CMC). The analogue is BLANOSE Cellulose Gum. Conforms to the requirements of the European Pharmacopoeia and the US Pharmacopoeia.

- hydroxypropyl cellulose (GOC). Analogue "KLUZEL Farm". Combines thermoplasticity and surface activity, as well as stabilizing properties.

As a preservative, sodium parabens that are compatible with Mexidol and well-proven, that meet the requirements of the Pharmacopoeia, methyl paraben, propyl paraben, etc.) are chosen. Other preservatives, such as propylene glycol and the like, are also possible.

As a stabilizer, the sodium salt of ethylenediaminetetraacetic acid used in the pharmaceutical industry can be used, the analogue is TRILON-B or another, similar in properties and action. Mexidol® (2-ethyl 6-methyl 3-hydroxypyridine succinate) is used as the active substance.

Wound healing agent is prepared as follows.

All the necessary components are prepared: a gel-forming base, a stabilizer, a preservative, the active substance is Mexidol and distilled water in a prescription amount.

The required amount of deionized distilled water is placed in a special reactor, it is heated to 70 ° C and, with constant stirring, a gelling base and a stabilizer are introduced.

Further, the preservative is dissolved in a separate container with stirring at room temperature, then Mexidol is added and stirred until the solution is completely transparent. The resulting solutions are mixed by stirring for two hours until complete transparency and uniformity of the system.

The resulting gel was cooled to room temperature. Measure viscosity and pH. The viscosity should be between 5.0 and 7.0.

Ready gel is packaged in metal or plastic tubes.

Example 1. The content of the components of the therapeutic composition, wt.%:

Sodium carboxymethyl cellulose 1.0 Sodium Methyl Paraben 0.01 Trilon B 0.01 Mexidol 0.1 Deionized water rest

First, methyl paraben is dissolved with stirring at room temperature until the solution is completely transparent (about 15 minutes). Then, Mexidol® is dissolved at room temperature and stirred until the solution is completely transparent. Then, in a separate container, water is heated to 40 ° C and Trilon B is dissolved with stirring until the solution is completely transparent, then the resulting solution is heated to 70 ° C and, with vigorous stirring, carboxymethyl cellulose is poured and stirred for two hours until the system is completely transparent and uniform. Add the previously obtained solution to the resulting solution and mix for 10 minutes. The prepared gel is cooled to room temperature. Next, measure the viscosity and pH of the gel. gel pH = 5.0-7.0.

Example 2. The content of the components of the therapeutic composition, wt.%:

Sodium carboxymethyl cellulose 5.0 Sodium Propyl Paraben 1.0 Trilon B 0.8 Mexidol 10.0 Deionized water rest

First, methyl paraben is dissolved with stirring at room temperature until the solution is completely transparent (about 15 minutes). Then, Mexidol® is dissolved at room temperature and stirred until the solution is completely transparent. Then, in another container, water is heated to 40 ° C and Trilon B is dissolved with stirring until the solution is completely transparent, then the resulting solution is heated to 70 ° C and, with vigorous stirring, carboxymethyl cellulose is poured and stirred for two hours until the system is completely transparent and uniform. Add the previously obtained solution to the resulting solution and mix for 10 minutes. The prepared gel is cooled to room temperature. Next, measure the viscosity and pH of the gel. gel pH = 5.0-7.0.

The composition is a homogeneous plastic mass, withstands shelf life without changing the microbiological, physico-chemical properties of at least 2 years.

Experimental tests of a wound healing agent are given.

In order to identify the effect of the gel on tissue epithelization, mice were used in the experiment. The wound was applied with a scalpel to the shaved surface of the mouse skin. The depth of the wound was about 0.8 mm, the length of the wound was 3 mm. Already on the first day after application of the gel, a scab began to form, on the third day the edges of the wound completely converged, the skin regained its elasticity on the 7th day.

To study the activity of the gel in burns of ST degree and in case of muscle-plane wound, standard rat models were used. The experiment showed that the gel has a pronounced wound healing effect in the initial phase of the wound process and provides earlier terms for the complete healing of wounds compared to the standard multicomponent ointments.

Also, the gel was used to prepare the wound surface for free skin grafting in case of burns of the 2-ZB degree. After a good condition of the granulated tissue was noted, skin grafting was performed. Graft engraftment was 100%.

It should be noted the self-epithelization of areas of the wound surface not covered by a skin graft, the absence of rough scars. The tests were carried out with all selected gelling bases.

Tests have shown high clinical efficacy of the proposed wound healing agent. Thus, a universal composition with Mexidol was developed, which is quite simple and technologically reproducible, which meets all the requirements of the pharmaceutical and cosmetic industries, which can be recommended for widespread use for the treatment of wounds, erosions, trophic ulcers, burns, pressure sores and other injuries of the skin and mucous membranes, especially complicated by purulent-inflammatory processes.

The gel can also be used to improve tissue trophism with varicose veins of the lower extremities, bruises, edema, hematomas, and to improve the structure of the skin.

Claims (1)

A wound healing agent, including a gelling agent, an active substance and distilled water, characterized in that Mexidol (2-ethyl 6-methyl 3-hydroxypyridine succinate) is used as the active substance in the following ratio, wt.%: Gelling agent 0.5-5.0 Stabilizer 0.01-0.8 Preservative 0.01-1.0 Mexidol 0.01-10.0 Distilled water deionized Rest