RU2397752C2 - Ointment "argolon" for treating infected wounds - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and pharmacology, namely to compositions for infected wounds treatment. Application of ointment: for treatment of post-operational wounds, as well as old, abundantly seeded with pathogenic microflora wounds, difficult or impossible to heal, turning trophic. Ointment based on gel based on various polyethylene oxides (PEO-400, 1500, 2000, 4000) contains active substances: stabilised zol of silver nanoparticles and proteolytic means - chymopsin, trypsin, chymotrypsin.

EFFECT: invention adds to ointment prolonged synergetic medicinal and antiseptic effect.

8 ex, 1 tbl

Description

The invention relates to medicine and pharmacology, in particular to compositions for treating infected wounds.

The invention can be used to treat postoperative wounds, as well as old, heavily seeded pathogenic microflora wounds, difficult or not amenable to healing, turning into trophic.

Known ointment "Oksizon" (FS 42-2246-84) for the treatment of skin lesions, eczema, infected wounds. The preparation is made on a vaseline basis and contains oxytetracycline dihydrate, 3.0 wt.% (Antibiotic), and hydrocortisone acetate, 1.0 wt.% (Anti-inflammatory agent) as active substances. However, the Vaseline ointment base "Oksison" does not provide a sufficiently effective transport function of the active components to the infected area. It should also be noted that the antibiotic (oxytetracycline dihydrate) does not have a wide spectrum of action on pathogenic microflora.

Also known is an ointment for the treatment of purulent wounds (Pat. RU 2146127, 2000), containing 0.07-0.48 wt.% Colloidal silver, stabilizer-polyvinylpyrrolidone - 0.93-5.52 wt.% And the base - gel polyethylene oxide - 1500. Colloidal silver as an antibacterial substance has a wider spectrum of exposure to pathogens than antibiotics. However, the use of colloidal silver without any anti-inflammatory compounds does not accelerate repair processes in chronic wounds, and it is also not effective with a high degree of bacterial contamination and a variety of types of pathogenic microflora.

Closest to the patented invention is the ointment "Hydropent" (Pat. RU 2233652, 2003).

Specified as a prototype, the drug is intended for the treatment of infected wounds and contains colloidal silver - 0.24-0.40 wt.%; polyvinylpyrrolidone - 2.76-4.60 wt.%; propolis - 0.80-0.90 wt.%; metronidazole - 0.90-0.95 wt%; a mineral based on aluminosilicates - 5.0-18.0 wt.%; polyethylene oxide-1500 gel - the rest. Ointment has a wide spectrum of effects on both gram-positive and gram-negative pathogenic microorganisms, including staphylococci and anaerobic strains. However, the antiseptic metronidazole is included in the ointment, which, as recent toxicological studies show, is unsafe for the central nervous system, blood-forming organs, and the gastrointestinal tract. Colloidal silver, which is part of the prototype, exhibits antibacterial activity against the polyassociate of pathogenic microflora. However, the relatively large particle size of silver (1-10 microns), and, therefore, the underdeveloped mass transfer surface does not allow the antiseptic properties of this active substance to be maximized.

The task of the invention is to increase the healing efficiency of infected wounds with the simultaneous exclusion of toxic components from the composition of the preparation.

This task is achieved by the fact that in order to heal infected wounds containing a wide variety of microorganism strains, active substances are introduced into the ointment that enhance each other's influence on the pathogenic microflora in the wound, as well as expand the spectrum of suppressed varieties of pathogenic microorganisms.

The inventive preparation is an ointment based on a gel of polyethylene oxides (PEO) grades 400, 1500, 2000, 4000, containing active substances - a stabilized sol of silver nanoparticles, trypsin, chymotrypsin, chymopsin in the following ratio, wt.%:

PEO-400 40.0-50.0 PEO-1500 10.0-15.0 PEO-2000 0,0-10,0 PEO-4000 0,0-5,0 Stabilized sol silver nanoparticles 7.0-10.0 Chymopsin 0.1-0.3 Trypsin 0,0-0,2 Chymotrypsin 0.1-0.2 Water up to 100

The introduction of the claimed ointment of chymopsin (trypsin, chymotrypsin) is aimed at facilitating the breakdown of necrotic tissues and fibrinous formations, thinning viscous secretions, wound exudate, blood clots.

The inclusion in the inventive preparation of a stabilized sol of silver nanoparticles due to the extremely small particle size (2-20 nm) and, as a result of this highly developed mass transfer surface, significantly enhances the effect of suppressing pathogenic microflora. In connection with the gradual release of active silver as a result of the interaction of nanoparticles with wound exudate, prolongation of the antiseptic properties of the ointment proposed for patenting is achieved. In addition to their antimicrobial properties, silver particles act as a preservative in the composition.

The ointment base - a gel based on a combination of polyethylene oxides of various molecular weights - also carries an additional function - transporting the active substances of the ointment deep into the infected area.

The technological process for preparing the ointment for the treatment of infected wounds "Argolon" is carried out in a reactor equipped with a combined stirrer, a jacket for heating / cooling and an external homogenizer with a recirculation loop. The process proceeds at a temperature of 60 to 35 ° C with continuous homogenization and evacuation. Evacuation allows to reduce the oxygen content in the ointment to a minimum, as a result of which the possibility of oxidation of active substances is sharply reduced and, accordingly, the shelf life of the claimed ointment is increased.

Ointment is packaged on a filling machine in plastic tubes of 30 g each.

Production safety is stipulated by the relevant sections of the regulation and safety instructions. To ensure sanitary standards, the premises where the ointment is manufactured, packaged, and packaged are equipped with supply and exhaust ventilation, an air conditioning system, and bactericidal UV lamps. According to the degree of fire and explosion hazard, the production of ointment belongs to the category “B”, according to sanitary design standards - non-toxic, according to the rules of electrical installations - non-explosive. By-products, wastewater, and air emissions from the production of ointment are absent.

Example 1. Preparation of ointment (per 100 wt.%) Under aseptic conditions, when heated, 50 wt.% PEO-400, 10 wt.% PEO-1500, 3 wt.% PEO-4000 are mixed, cooled, a mixture of 7 wt. % stabilized sol of silver nanoparticles with 0.2 wt.% chymopsin, adjusted to 100 wt.% with water and mixed with simultaneous homogenization. The test results of the drug are shown in the table (example 1).

Example 2

While maintaining the conditions of example 1 take 45 wt.% PEO-400, 15 wt.% PEO-1500, 5 wt.% PEO-2000, 0.2 wt.% Trypsin.

Example 3

While maintaining the conditions of example 1 take 40 wt.% PEO-400, 15 wt.% PEO-1500, 6 wt.% PEO-2000, 2 wt.% PEO-4000, 10 wt.% Stabilized sol of silver nanoparticles, 0.2 wt.% chymotrypsin.

Example 4

While maintaining the conditions of example 1 take 45 wt.% PEO-400, 10 wt.% PEO-1500, 5 wt.% PEO-2000, 1 wt.% PEO-4000, 10 wt.% Stabilized sol of silver nanoparticles, 0.3 wt.% chymopsin.

Example 5

While maintaining the conditions of example 1 take 40 wt.% PEO-400, 15 wt.% PEO-1500, 10 wt.% PEO-2000, 2 wt.% PEO-4000, 7 wt.% Stabilized sol of silver nanoparticles, 0.2 wt.% chymotrypsin.

Example 6

While maintaining the conditions of example 1 take 40 wt.% PEO-400, 15 wt.% PEO-1500, 10 wt.% PEO-2000, 2 wt.% PEO-4000, 7 wt.% Stabilized sol of silver nanoparticles, 0.1 wt.% chymotrypsin, 0.1 wt.% trypsin.

Example 7

While maintaining the conditions of example 1 take 45 wt.% PEO-400, 10 wt.% PEO-1500, 5 wt.% PEO-2000, 1 wt.% PEO-4000, 10 wt.% Stabilized sol of silver nanoparticles, 0.1 wt.% chymopsin, 0.1 wt.% chymotrypsin, 0.1 wt.% trypsin.

For comparison, the table shows the test results of the ointment prototype (example 8).

The antibacterial activity of the drugs was studied on clinical strains of conditionally pathogenic microorganisms (gram-positive and gram-negative), isolated in various purulent-inflammatory processes. For comparison, the sensitivity of the aforementioned microorganisms to the prototype ointment was determined.

The test results (table) indicate that due to the synergistic effect of silver nanoparticles in combination with chymopsin (trypsin, chymotrypsin) and a spasmodic increase in the mass transfer surface of active silver, the patented ointment exhibits significantly stronger antibacterial properties than the prototype ointment for all fourteen varieties of pathogenic microflora .

Table Test results of ointments for the treatment of infected wounds (sensitivity of pathogenic microorganisms to the drug) Culture The number of strains Inhibition of microflora, rel.% / Abs. Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 (prototype) Escherichia coli fourteen 93/13 64/9 93/13 86/12 71/10 86/12 93/13 50/7 Enterobacter 3 67/2 67/2 100/3 67/2 67/2 67/2 100/3 33/1 Enterococcus faecalis 9 67/6 56/5 78/7 67/6 89/8 78/7 89/8 56/5 Haffnia alvei 3 33/1 66/2 100/3 66/2 66/2 66/2 100/3 33/1 Klebsiella oxytoca 7 71/5 71/5 57/4 86/6 57/4 71/5 86/6 43/3 Klebsiella pneumoniae 8 100/8 63/5 100/8 75/6 100/8 88/7 88/7 63/5 Morganella morganii 3 100/3 100/3 100/3 100/3 100/3 100/3 100/3 33/1 Pseudomonas aeroginosa 5 40/2 80/4 60/3 100/5 60/3 80/4 100/5 40/2 Staphylococcus aureus twenty 70/14 60/12 85/17 80/16 90/18 75/15 85/17 50/10 Staphylococcus epidermis eleven 100/11 73/8 82/9 73/8 100/11 91/10 82/9 64/7 Staphylococcus hyicus 3 67/2 100/3 100/3 67/2 100/3 100/3 100/3 33/1 Staphylococcus haemolyticus 13 100/13 62/8 92/12 92/12 77/10 85/11 77/10 46/6 Total 106 78/83 65/69 85/90 81/86 82/87 76/81 82/87 47/50

Claims (1)

An ointment for the treatment of infected wounds, containing polyethylene oxides - 400, 1500, 2000, 4000 and water as the basis, characterized in that instead of colloidal silver, a stabilized sol of silver nanoparticles is used and additionally proteolytic compounds - chymopsin, trypsin, chymotrypsin with a ratio of components, wt .%:
PEO-400 40.0-50.0 PEO-1500 10.0-15.0 PEO-2000 0,0-10,0 PEO-4000 0,0-5,0 Stabilized sol silver nanoparticles 7.0-10.0 Chymopsin 0.1-0.3 Trypsin 0,0-0,2 Chymotrypsin 0.1-0.2 Water Up to 100