RU2218167C2 - Method for preparing composite agent "ointment "svf" - Google Patents

Abstract

FIELD: medicine, veterinary science. SUBSTANCE: invention relates to agent for treatment of infected wounds that contains bee honey, furacillin, methyluracil, 3-substituted sodium citrate, succinic acid, phosphaden, sea-buckthorn oil, vinyline, polyvinylpyrrolidone and distilled water in the following ratio of components, wt. -%: bee honey, 83.2-83.6; furacillin, 0.4-0.41; methyluracil, 3.0-3.1; 3-substituted sodium citrate, 0.02-0.04; succinic acid, 0.04-0.05; phosphaden, 0.001-0.0012; sea-buckthorn oil, 5.0-5.1; vinyline, 1.0-1.1; polyvinylpyrrolidone, 5.9-6.0; distilled water, up to 100. Invention can be used for preparing ointments and their following using in treatment of infected wounded. EFFECT: enhanced effectiveness of composition. 1 tbl, 3 ex

Description

 The invention relates to medicine and veterinary medicine and can be used to obtain ointments and their subsequent use in the treatment of infected wounds.

A known method of composition is Konkova ointment intended for the treatment of sluggish wounds and pyoderma. A method of obtaining this composite substance is to maintain a composition consisting of honey and a fat base - fish oil, the antimicrobial component of rivanol in the following ratio, wt.%:
Rivanol - 0.3 g
Bee honey - 63.2 g
Fish oil - 35 g
Distilled water - 1.5 g
(M.D. Mashkovsky. Medicines. Kharkov: Torsing, 1998, Volume 2).

 A significant disadvantage of the known method for producing the prototype is that rivanol introduced into its composition exhibits antimicrobial activity, mainly in relation to coccal microflora (I.S. Chekman et al., 1987; M.D. Mashkovsky, 1998). In addition, and in honey, antimicrobial properties are manifested mainly against gram-positive microorganisms (T.V. Vakhonina. Bee pharmacy. - St. Petersburg: Agropromizdat, 1992, p. 190).

 But the wound process is often complicated by gram-negative microflora.

 The disadvantage of this method is that rivanol refers to substances with a very high degree of cytotoxic effect (G.P. Chervonskaya et al. Cytotoxic effect of chemicals contained in the form of impurities and some medical immunological preparations. "ZhMEI", 1988, p. 85-90).

The rivanol content in the prototype is 0.3% (3 mg / ml), which is higher than its cytopathogenic effect (CPP ₁₀₀ ) - 2.5 μg / ml more than 1000 times. This means that rivanol is pharmacologically incompatible with other components of the prototype.

 According to the recommendations of the WHO Expert Committee on Standardization of Biological Substances, they should not contain potentially hazardous chemicals (WHO, Technical Report Series, 1982, 636, pp. 45-86). Fish oil - a product from a unique scarce raw material of animal origin - gives the ointment an unpleasant odor.

 Given these disadvantages of the prototype - Konkova ointment, the objective of the invention is to increase the effectiveness of the composition.

The essence of the proposed method is that the task is solved by introducing into the composition containing honey bee and a fat base - sea buckthorn oil, and instead of the antimicrobial component of rivanol - furatsilin and additionally methyluracil, sodium citrate, succinic acid, phosphaden, vinylin and polyvinylpyrrolidone in the following ratio of components , wt.%:
Bee honey - 83.63-83.17
Furatsilin - 0.4-0.41
Methyluracil - 3.0-3.1
Sodium citrate 3-substituted - 0.02-0.04
Succinic acid - 0.04-0.05
Phosphaden - 0.001-0.0012
Sea buckthorn oil - 5.0-5.1
Vinylinum - 1.0-1.1
Polyvinylpyrrolidone - 5.9-6.0
Distilled Water - Else
The technical result achieved is an increase in the antimicrobial activity of the composition by introducing at a specified dose furatsilina, not decreasing in the presence of synergistically trophically active preparations, emollients and formative components in the indicated concentrations.

 The composition can be widely used in medicine and veterinary medicine as a means to accelerate the healing of infected wounds.

The properties of the present invention are:
- novelty - the introduction of furatsilin in the composition in 0.4-0.41% concentration increases its antimicrobial activity, which does not decrease with the additional introduction of synergistically trophically active methyluracil, citrate, succinate, phosphaden, vinylin and polyvinylpyrrolidone,
- the inventive step is confirmed by the progressiveness of the known methods and non-obviousness (in the analysis we did not find the use of this method to obtain the composition as a wound healing agent in medicine and veterinary medicine),
- The obvious possibility of mass production for the purposes of medicine and veterinary medicine, the availability of serial use.

 The method is carried out by mixing the components. The antimicrobial activity of Konkova ointment and the proposed compositions was evaluated in vitro by agar diffusion, for which filter paper disks (d = 6 mm) were impregnated with the test composition and tweezers were applied to the surface of the test medium-infected microbes at the same distance from each other (Tentsova A I., Gretsky V.M. Modern aspects of research and production of ointments. - M .: Medicine, 1980. - 192 p.).

 As test microbes, 24-hour cultures of E. coli strains (ATCC 25922) and St. aureus (ATCC 25923), as well as strains of E. coli, St. aureus, Ps. aeroginose and other bacterial isolates, including those resistant to many antimicrobial agents.

 The initial version of the test product was, like the prototype, a 3-component composition containing bee honey, sea buckthorn oil (instead of fish oil deficient with an unpleasant odor) and an antimicrobial component with a wide spectrum of bactericidal action. As the latter, we tested many preparations known to us with such properties (antibiotics, nitrofurans, and other agents that turned out to be effective in our composition). In addition to the compositions previously tested in this way, agents that increased tissue trophism were additionally sequentially introduced: methyluracil, sodium citrate, succinic acid, phosphaden and vinylin — giving the ointment the ability to maintain tissue elasticity, as well as polyvinylpyrrolidone — form-forming, which prevents the separation of the components of the ointment, strengthens its film-forming property when application to the wound. In this composition, stable bactericidal activity against gram-positive and gram-negative microorganisms was preserved only in furatsilin and gentamicin. A mixture of 0.2% furatsilin and 0.2% gentamicin in such a composition showed increased bactericidal activity due to the synergism known for these agents, but, like separately taken in the ointment, 0.2% furatsilin and 0.2% gentamicin, it did not antimicrobial properties on Pseudomonas aeruginosa isolates. It was possible to achieve an antimicrobial and only bacteriostatic effect with respect to this microorganism only by doubling the concentration of furatsilin taken separately and mixed with gentamicin. Taken separately, gentamicin in double concentration in the composition did not have such an effect. Thus, by the method of the only similarities and differences, the desired stable antimicrobial effect was achieved by introducing furatsilin in the composition at a concentration of 0.4-0.41%. The decrease in the concentration of the drug below the specified led to an unstable bacteriostatic effect against Pseudomonas aeruginosa. The achieved bacteriostatic effect did not change in relation to this pathogen and others with a further increase in the concentration of furacilin in the ointment.

 Prepare ointment "SVF" by simple mixing in the following sequence.

 Example 1

Bee honey - 83.6
Furacilin - 0.4
Methyluracil - 3.0
Sodium citrate 3-substituted - 0.02
Succinic acid - 0.04
Phosphaden - 0.001
Sea buckthorn oil - 5.0
Vinylinum - 1.0
Polyvinylpyrrolidone - 5.9
Distilled water - Up to 100 g
In the ointment compiled according to example 1, the concentration of furatsilina is minimal, at which the bacteriostatic effect is preserved in relation to isolates of Pseudomonas aeruginosa.

 Example 2

Bee honey - 83.43
Furacilin - 0.405
Methyluracil - 3.05
Sodium citrate 3-substituted - 0.03
Succinic acid - 0.045
Phosphaden - 0.0011
Sea buckthorn oil - 5.05
Vinylinum - 1.05
Polyvinylpyrrolidone - 5.95
Distilled water - Up to 100 g
In the composition compiled according to this option, the concentration of furatsilina is optimal, the ointment has a wide range of antimicrobial properties and a stable bactericidal effect against Pseudomonas aeruginosa.

 Example 3

Bee honey - 83.2
Furacilin - 0.41
Methyluracil - 3.1
Sodium citrate 3-substituted - 0.04
Succinic acid - 0.05
Phosphaden - 0.0012
Sea buckthorn oil - 5.1
Vinylinum - 1.1
Polyvinylpyrrolidone - 6.0
Distilled water - Up to 100 g
In the composition compiled according to example 3, the content of furatsilina maximum, above this concentration, the bactericidal and bacteriostatic effectiveness of the drug does not increase.

 Materials of antimicrobial activity of Konkova ointment and "SVF" ointment are presented in the table (see the end of the description) ..

 As can be seen from the table, Konkova ointment really shows activity against coccal microflora and does not inhibit the growth of gram-negative microorganisms and Pseudomonas aeruginosa on a burn. At the same time, ointment "SVF" in various forms has a wide range of bactericidal and bacteriostatic effects. It was found that gentamicin significantly enhances the bactericidal effect of furatsilin in this composition due to the known synergism. However, gentamicin does not inhibit the growth of Pseudomonas aeruginosa alone and in combination with furacilin. The composition shows a stable bacteriostatic effect in relation to Pseudomonas aeruginosa strains with an increased content of furatsilin in ointment (up to 0.4-0.41%). A further increase in the concentration of furatsilin did not increase the antimicrobial effect, which indicates the advisability of a further increase in the concentration of this drug.

Long-term tests of the SVF ointment showed that the achieved antimicrobial effect on many isolates of microbes from hospital patients and animals is preserved when the drug is stored in the refrigerator at a temperature of + (2-4) ^o C for a year.

 The resulting ointment is yellow (various shades) in color, with a pleasant smell of bee honey, is stable when stored in the refrigerator.

 In experiments on rabbits and white rats, it was found that the ointment does not change the state of the mucous membranes of the eyes and cornea, as well as the functions of vision with 10 times in a row exposure to the ointment once a day. In patients with nonspecific acute and chronic conjunctival kearatitis of calves, the ointment had a pronounced therapeutic effect.

 When treating operative infected wounds in white rats and dog puppies, it was found that “SVF” ointment, in contrast to Konkova ointment, suppresses exudation, forms a film on the surface of the wound, under which, as under a scab, healing is more intense than when exposed to Konkova ointment . Thus, the ointment "SVF" along with a large antimicrobial effect and has greater wound healing activity, and can also be used as an ophthalmic agent in veterinary practice.

Claims (1)

A method of obtaining an agent for treating infected wounds containing bee honey, a fat base, an antimicrobial preparation and distilled water, characterized in that sea buckthorn oil is taken as a fat base, furatsilin is an antimicrobial preparation, and methyluracil, sodium 3-substituted citrate, is additionally administered amber, phosphaden, vinylin, polyvinylpyrrolidone in the following ratio, wt.%: Bee honey 83.2-83.6 Furatsilin 0.4-0.41 Methyluracil 3.0-3.1 Sodium citrate 3-substituted 0.02-0.04 Succinic acid 0.04-0.05 Phosphaden 0.001-0.0012 Sea-buckthorn oil 5.0-5.1 Vinylinum 1.0-1.1 Polyvinylpyrrolidone 5.9-6.0 Distilled water Up to 100

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