RU2472490C1 - Soft dosage forms for treating skin purulent infections, formulations and methods for preparing - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an agent for treating skin purulent infections, containing microcrystalline fusidic acid, an emulsion base (butylhydroxyanisol, emulsifier No.1, distilled glycerol, Vaseline oil, potassium sorbate, tween 80, medical white Vaseline, purified water) and additionally zinc oxide. The invention also concerns methods for preparing the specified agent.

EFFECT: developing an integrated preparation for treating purulent skin infections on the emulsion base that enables higher therapeutic effectiveness and reduced length of treatment.

3 cl, 2 tbl, 6 ex

Description

The invention relates to the field of pharmaceuticals and medicine, namely to external agents for the treatment of purulent skin infections.

The wide distribution of Gram (+) pathogens, especially methicillin-resistant staphylococci, makes it necessary to reconsider the attitude to such an “old” drug as fusidic acid and to pay attention to the possibility of its use in the treatment of infections caused by these microorganisms.

Fusidic acid (FC) - C ₃₁ H ₄₈ O ₆ × 1/2 H ₂ O (molecular weight - 525.7) is a tetracyclic triterpenoid in chemical structure. It is produced by Fusidium coccineum fungi and is the only representative of the fusidan class used in clinical practice.

FC was first isolated in 1960 by specialists from Leo Laboratories (Denmark). Since 1962, it has been used in the treatment of both systemic and superficial staph infections.

The spectrum of antimicrobial activity of FC is unique, since within the same genus different types of microorganisms may have different sensitivity to FC preparations. The highest activity of FC is against Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-resistant strains. On most other types of staphylococci and streptococci, it acts moderately, highly active against corynebacteria, meningococci and neisseria. Gram (-) aerobic sticks are overwhelmingly resistant to FC. FC has high activity against Gram (+) anaerobes, including clostridia, peptococci, peptostreptococci, is significantly less active against Gram (+) anaerobes, such as bacteroids and fusobacteria, and some activity against a number of protozoa, including Ciardia lamblia and Plasmodium falciparum.

Interest in fusidic acid is also attracted by the fact that the number of strains resistant to it does not increase. According to foreign researchers, the frequency of FC resistance in methicillin-sensitive strains of S. aureus is 1-3%, similar indicators for methicillin-resistant strains are slightly higher - 2-5.7%.

FC is used in the treatment of a number of infections of the skin and soft tissues, including pustular skin diseases, acne, abscesses, wound and burn infections, and a secondary infection against the background of scabies and insect bites.

Such widespread use of the drug is explained by its high activity against the most likely pathogen - S. aureus, including methicillin-resistant strains. FC is one of the drugs of choice for secondary infection of atopic dermatitis, as more than 90% of patients with this pathology have staphylococcal skin colonization.

When comparing the activity of FC with other antibiotics, it was found that in the treatment of superficial skin infections it is not inferior to mupirocin (clinical efficacy is 94-95.2 and 97-98%, respectively)

A known drug having antimicrobial and regenerative effects, containing fusidine sodium, methyluracil, sodium pyrosulphuric acid, polyvinylpyrrolidone, lanolin, petrolatum, distilled water (patent RU 2180216). The composition has an imperfect vaseline-lanolin base.

Famous domestic drug for the treatment of purulent skin infections - gel "Prefusin" containing fusidic acid and prednisone. The gel base forms a thin film on the skin, which has a protective effect in small wounds, at the same time painfully tightens the tissue, making it difficult for pus to drain in case of serious skin lesions, increasing the duration of treatment.

Emulsion ointment foundations are widely used in medical practice. The works of domestic and foreign authors have proved that ointments prepared on emulsion bases are well absorbed by the skin and easily release the medicinal substances introduced into them. This is due to the fact that the flow of drugs into the body occurs mainly as a result of the conversion of fatty bases into a stable water-in-oil emulsion, similar in composition to skin fat [4]. In addition, emulsion bases soften and swell the epithelial layer, which also contributes to better absorption of drugs into the skin. The use of emulsion bases together with this reduces the need for fatty bases, which are food products, and significantly reduces the cost of ointments.

As a prototype, the foreign drug Fucidin manufactured by Leo Laboratories Limited (Ireland) was selected - an external cream on an emulsion basis, which includes fusidic acid. The drug is used to treat bacterial skin infections.

The objective of the present invention is to develop a drug for the treatment of purulent skin infections on an emulsion basis, which will significantly increase the effectiveness of therapy and reduce treatment time.

The problem is solved in that the proposed preparation contains microcrystalline fusidic acid, distilled glycerin, liquid paraffin, medical petrolatum, emulsifier No. 1, polysorbate 80, potassium sorbate, butyl hydroxyanisole, purified water, additionally zinc oxide (option), in the following ratio of components, g:

Fusidic acid microcrystalline 1.8-2.2 Zinc oxide 0,0-5,0 Butylhydroxyanisole 0.001-0.002 Emulsifier number 1 5.0-15.0 Glycerol (glycerin distilled) 9.0-20.0 Liquid paraffin (liquid paraffin) 1.0-5.0 Potassium sorbate 0.1-0.3 Polysorbate-80 (twin-80) 0.5-1.5 Vaseline medical white 8.0-15.0 Purified water up to 100

Zinc oxide in the composition of a soft dosage form has an anti-inflammatory dermatotropic, drying effect. It reduces the effects of exudation, inflammation and irritation of tissues, forms a protective barrier against irritating factors, and softens irritated skin. Zinc oxide also has an adsorbing, astringent and antiseptic effect, forms albuminates and denatures proteins.

The indicated ranges of concentrations of the active ingredients are optimally acceptable and pharmacologically significant.

Example 1

56.6 g of purified water are mixed with 20.0 g of distilled glycerol, 0.5 g of polysorbate-80, 5.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° C, stirred, dissolved in 0.1 g of potassium sorbate ( mixture 1). 15.0 g of petrolatum are melted, 1.0 g of paraffin oil, 0.001 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 1.8 g of fusidic acid is mixed with 5.4 g of mixture 3, mixed until homogeneous (mixture 4). Mixture 3 and mixture 4 are combined, altered to homogeneity, packaged in tubes.

Example 2

64.15 g of purified water is mixed with 10.0 g of distilled glycerol, 0.7 g of polysorbate-80, 7.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° C, stirred, dissolved 0.15 g of potassium sorbate ( mixture 1). 11.0 g of petroleum jelly are melted, 1.0 g of petrolatum oil, 0.001 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 2.0 g of fusidic acid is mixed with 2.0 g of liquid paraffin and 2.0 g of distilled glycerin, mixed until homogeneous (mixture 4). Mixture 3 and mixture 4 are combined, alter to homogeneity, packaged in tubes.

Example 3

63.6 g of purified water are mixed with 10.0 g of distilled glycerol, 1.0 g of polysorbate-80, 10.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° С, stirred, 0.2 g of potassium sorbate is dissolved ( mixture 1). 8.0 g of petroleum jelly are melted, 1.0 g of petrolatum oil, 0.002 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 2.2 g of fusidic acid is mixed with 4.0 g of liquid paraffin, and mixed until uniform (mixture 4). Mix 3 and mixture 4 are combined, mixed until homogeneous, packaged in tubes.

The resulting drug is stable during storage, meets the requirements of the pharmacopoeia and has a shelf life of 2 years (table 1).

Example 4

56.6 g of purified water are mixed with 15.0 g of distilled glycerol, 0.5 g of polysorbate-80, 15.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° C, stirred, dissolved in 0.1 g of potassium sorbate ( mixture 1). 8.0 g of petroleum jelly are melted, 1.0 g of petrolatum oil, 0.001 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 1.8 g of fusidic acid is mixed with 3.6 g of mixture 3, mixed until homogeneous (mixture 4). 5.0 g of zinc oxide are mixed with 10.0 g of mixture 3, mixed until homogeneous (mixture 5). Mixture 3, mixture 4 and mixture 5 are combined, altered to homogeneity, packaged in tubes.

Example 5

55.8 g of purified water are mixed with 10.0 g of distilled glycerol, 1.0 g of polysorbate-80, 12.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° С, stirred, 0.2 g of potassium sorbate is dissolved ( mixture 1). 11.0 g of petroleum jelly are melted, 1.0 g of petrolatum oil, 0.001 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 2.0 g of fusidic acid is mixed with 2.0 g of liquid paraffin and 2.0 g of distilled glycerin, mixed until homogeneous (mixture 4). 3.0 g of zinc oxide is mixed with 6.0 g of mixture 3, mixed until uniform (mixture 5). Mixture 3, mixture 4 and mixture 5 are combined, altered to homogeneity, packaged in tubes.

Example 6

58.1 g of purified water are mixed with 7.0 g of distilled glycerol, 1.5 g of polysorbate-80, 9.0 g of emulsifier No. 1, heated to a temperature of 70-80 ° С, stirred, 0.2 g of potassium sorbate is dissolved ( mixture 1). 14.0 g of petrolatum are melted, 1.0 g of paraffin oil, 0.002 g of butylhydroxyanisole are added, stirred, heated to 70-80 ° С (mixture 2). Mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3). 2.2 g of fusidic acid is mixed with 2.0 g of liquid paraffin and 2.0 g of distilled glycerin, mixed until uniform (mixture 4). 1.0 g of zinc oxide is mixed with 2.0 g of liquid paraffin, mixed until uniform (mixture 5). Mix 3, mix 4 and mix 5 are combined, mixed until homogeneous, packaged in tubes.

The resulting drug is stable during storage, meets the requirements of the Pharmacopoeia and has a shelf life of 2 years (table 2).

Information sources

1. Yu.A. Belkova. Fusidic acid in modern clinical practice. Clinical microbiology and antimicrobial chemotherapy. No. 4, Volume 3, 2001.

2. Patent RU 2180216.

3. Mashkovsky M.D. Medicines Vol. 15. New Wave LLC, 2005, p. 739.

4. T.P. Korobko, A.A. Tsofina, Pharmacology with the recipe, M., Medicine, 1967.

5. Register of medicines, CLIFAR, CD.

Table 1 Table of analytical data on the quality and stability of the drug Description pH Particle size Uniformity Foreign matter quantitation Cream white or white with a yellowish tint from 5.0 to 8.5 No more than 60 microns No less than three samples should not have visible particles. Not more than 5.0% (HPLC) Not less than 1.8% and not more than 2.2% (HPLC) at the time of manufacture Etc. one Cream white with a yellowish tint 6.3 50,0 homogeneous 0.48 1.83 Etc. 2 Cream white with a yellowish tint 6.0 56.0 homogeneous 0.49 1.96 Etc. 3 Cream white with a yellowish tint 6.4 54.0 homogeneous 0.50 2.08 after 2 years of storage - at the end of the expiration date Etc. one Cream white with a yellowish tint 6.0 56.0 homogeneous 0.51 1.80 Etc. 2 Cream white with a yellowish tint 6.4 53.0 homogeneous 0.48 1.88 Etc. 3 Cream white with a yellowish tint 6.3 55.0 homogeneous 0.50 1.98

table 2 Table of analytical data on the quality and stability of the drug Description pH Particle size Foreign matter quantitation Cream white or white with a yellowish tint from 5.0 to 8.5 No more than 60 microns Not more than 5.0% (HPLC) Fusidic acid - not less than 1.8% and not more than 2.2% Zinc oxide - not more than 5.0% at the time of manufacture Etc. four White cream 7.3 39.5 0.85 1.82 4.9 Etc. 5 White cream 7.1 43.0 0.88 1.95 3.2 Etc. 6 White cream 7.0 41.2 0.87 1.99 1.8 after 2 years of storage - at the end of the expiration date Etc. four White cream 7.0 40,0 0.97 1.80 4.7 Etc. 5 White cream 7.2 42.1 0.95 1.84 2.7 Etc. 6 White cream 7.1 46.0 0.99 1.90 1,5

Claims (3)

1. The agent for the treatment of purulent skin infections contains fusidic acid microcrystalline and emulsion base in the following ratio of components, g:
microcrystalline fusidic acid 1.8-2.2 zinc oxide 0,0-5,0 butylhydroxyanisole 0.001-0.002 emulsifier No. 1 5.0-15.0 distilled glycerin 10.0-20.0 Vaseline oil (liquid paraffin) 1.0-5.0 potassium sorbate 0.1-0.3 polysorbate-80 (twin-80) 0.5-1.5 medical white petrolatum 8.0-15.0 purified water up to 100 2. The method of obtaining the agent according to claim 1 is that the purified water is mixed with distilled glycerin, polysorbate-80, emulsifier No. 1, heated to a certain temperature, mixed, potassium sorbate is dissolved (mixture 1), petroleum jelly is melted separately, and liquid paraffin is added. oil, butylhydroxyanisole, stirred, heated (mixture 2), then mixture 1 and mixture 2 are mixed, homogenized, cooled (mixture 3), part of the resulting mass is combined with fusidic acid, mixed until homogeneous (mixture 4), zinc oxide is mixed with oil green, mix until smooth (mixture 5), after which the mixtures 3, 4, 5 are combined, mix until smooth, packaged in tubes. 3. The method of obtaining funds according to claim 1, characterized in that the purified water is mixed with distilled glycerin, polysorbate-80, emulsifier No. 1, heated to a certain temperature, stirred, potassium sorbate is dissolved (mixture 1), the petrolatum is melted separately, the petrolatum is added oil, butylhydroxyanisole, stirred, heated (mixture 2), then mixture 1 and mixture 2 were mixed, homogenized, cooled, after which part of the resulting mass was combined with fusidic acid, mixed until homogeneous, combined with the remaining mass, varied sew to a homogeneous state, packaged in tubes.