RU2752066C1 - Antibacterial ointment with alcoholic extracts of royal jelly and propolis - Google Patents

Abstract

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to an antibacterial agent. The antibacterial agent for the skin and mucous membranes in the form of an ointment contains 10% alcohol extract of propolis and 25% alcohol extract of royal jelly as active ingredients and an ointment base including RH40 cremophore, coconut oil or shea butter, emulsion wax, lutrol F-127 and purified water, with a certain ratio of components.

EFFECT: antibacterial agent has a pronounced and prolonged antibacterial, antioxidant effect, good fixation and uniform distribution on the mucous surface, convenient to use, without side effects.

1 cl, 3 dwg, 3 tbl, 3 ex

Description

The proposed invention relates to the field of medicine, namely to pharmacy, and concerns the development of an ointment containing royal jelly and an alcoholic extract of propolis, and can be used in the complex treatment of infectious and inflammatory diseases of the skin and mucous membranes (wounds, scratches, seizures).

Known synthomycin liniment 1%, 5% and 10%, containing the antibacterial active substance chloramphenicol and an ointment base containing castor oil, emulsifier No. 1, hydroxystearate macrogolglycerol, sorbic acid, sodium carmelose, purified water used for treatment and prevention of infectious and inflammatory diseases in surgery, dermatology and obstetrics and gynecology [Mashkovsky M.D. Medicines. 4.2. - M .: Medicine, 1993 .-- p. 303-304].

However, this agent has an antimicrobial, bacteriostatic effect, and the absorption of the drug when applied externally is negligible, does not have anti-inflammatory and prolonged action.

Known antibacterial agent in the form of an ointment, which contains, by weight. %: erythromycin 0.889-1.333, sodium sulfate pyro 0.009-0.011, anhydrous lanolin 36-44, medical petrolatum 53.1-64.8 [patent RU 2217147, 2003].

Known composition for external use for the treatment of wounds and destructive lesions of the mucous membrane and skin of mammals, containing an effective amount of nanoparticles of cerium oxide, a pharmaceutically acceptable carrier, which includes water-soluble cellulose derivatives and water-soluble polysaccharides of brown algae - pectin, fucoidin and alginate, at a certain ratio of components, and the target the additive is selected from a number of: immunomodulators, antibacterial drugs, stimulants of reparative processes, analgesics, anesthetics, anti-inflammatory agents, antioxidants, vitamins, polysaccharides or mixtures thereof [patent RU 2699362, 2019].

Known ointment for the treatment of wounds, including substances of plant origin, beeswax, pork fat, while as substances of plant origin it contains a crushed herbal mixture of St. John's wort, Veronica officinalis, burdock leaves, blackheads, leaves and stems of white lily, black root with a mass ratio of ingredients 1: 1: 1: 1: 1: 0.5, respectively, and additionally contains egg oil, grape seed oil at a certain ratio of components [patent RU 2706333, 2019].

The closest analogue of the present invention is an ointment for the prevention and complex treatment of acute respiratory viral infection caused by the influenza virus, containing as an active ingredient an alcoholic extract of large wax moth larvae and 10% alcoholic extract of propolis, as an ointment base - a copolymer of styrene with maleic anhydride, petroleum jelly, emulsifier T-2, Cremophor RH40 and lutrol F-68 and purified water at a certain ratio of components [patent RU 2477141, 2013].

The objective of the invention is to expand the arsenal of agents with antibacterial activity.

The technical result is the creation of a new drug of domestic production in the form of an ointment, which has a pronounced and prolonged antibacterial, antioxidant, anti-inflammatory and regenerating effect, with good fixation and uniform distribution on the mucous surface, easy to use, without side effects.

The proposed antibacterial agent for skin and mucous membranes in the form of an ointment contains 25% alcoholic extract of royal jelly and 10% alcoholic extract of propolis as active ingredients and an emulsion ointment base including coconut oil or shea butter, Cremophorus RH40, lutrol F-127 , emulsion wax and purified water, with the following ratio of the starting components, wt. %:

25% alcoholic extract of royal jelly 20.0 10% alcoholic extract of propolis 5.0 coconut oil or shea butter 20.0 Cremophor RH40 1.0 lutrol F-127 20.0 emulsion wax 2.0 purified water up to 100.0.

The invention is illustrated by the following materials: Table 1 shows the antimicrobial activity of the ointment according to examples 1-2. Table 2 shows the antioxidant activity of the ointment, namely the chemiluminescence indices in the model system that generates reactive oxygen species (ROS) when drugs are added. Table 3 shows the results of the total content of antioxidants in alcoholic and aqueous-alcoholic extracts of propolis and royal jelly. Figure 1 shows a record of chemiluminescence in a model system that generates ROS after adding drugs, where: 1-control, 2-alcoholic extract of royal jelly 25%, 3-alcoholic extract of propolis 10%. Figure 2 shows a record of chemiluminescence in a model system that generates ROS after adding drugs, where: 1-control + alcohol, 2-alcohol extraction from the ointment base according to example No. 1, 3-alcohol extraction from the ointment base according to example No. 2.

Figure 3 shows a record of chemiluminescence in a model system that generates ROS after adding drugs, where: 1-control, 2-water extraction from the ointment base according to example No. 1, 3-water extraction from the ointment base according to example No. 2.

All components that make up the ointment are approved for medical use.

Royal jelly contains: proteins (proteins) are mainly represented by albumin and globulins in a 2: 1 ratio; proteins of royal jelly are close to proteins of blood serum; carbohydrates (glucose, fructose, sucrose); vitamins A, D, C, B1, B2, B3, B6, B12, B15, H, E, PP, pantothenic acid; free fatty acids (15): succinic, palmitic, stearic, decenic, etc.; hormones (estradiol, testosterone, progesterone); pyruvic and lactic acids; mineral salts; trace elements; acetylcholine; sterols; lipids [http://spirkinmed.ru/index.php/produkty-pchelovodstva/matochnoe-molochko].

Propolis alcohol extract. The introduction of alcoholic extracts of propolis and royal jelly into the composition of the ointment simultaneously increases the antioxidant activity of the ointment, contributes to the manifestation of the antiviral, anti-inflammatory, reparative, prolonged effect of the ointment.

Lutrol F-127 (LutrolF-127), BASF (Germany) 9003-11-6, promotes prolongation of the active ingredient in the composition.

Cremofor RH-40 (Cremofor® RH-40) BASF (Germany) No. 013635 / 01-2002 oxyethylated hydrogenated castor oil, improves the structure of the solvent, increases the bioavailability of the active ingredients introduced into the composition due to surface-active properties.

Edible coconut oil - GOST 10766-64. Organic virgin coconut oil. Nutritious superfood suitable for indoor and outdoor use. Mild coconut aroma and flavor. Supports Brain Function Certified Organic by Quality Assurance International (QAI) and USDA Organic. Does not contain GMOs, hexane and pesticides. It can be used as an excipient in the production of soft medicines for external use. Manufactured in a third-party GMP facility. Coconut is a superfood with a subtle tropical aroma and flavor. Coconut oil is a rich source of medium chain triglycerides such as lauric, capric, and caprylic acids.

Shea Butter - (Shea Butter). The oil gained fame in cosmetology and medicine due to its composition, more than 80% are triglycerides - vegetable fats necessary for moisturizing and restoring cells. Also organic oil contains acids: oleic; stearic; palmitic; linoleic; linolenic. The smallest proportion (8%) of the content in shea butter is occupied by unsaponifiable substances: phenols; tocopherols; triterpenes; steroids; hydrocarbons. A small amount of terpene alcohols are present in the composition, which provide shea butter with a characteristic odor. Often this component is extracted from the natural environment and added as a fragrance to perfumery and cosmetics. Promotes penetration into the skin, the coating on the skin prevents the penetration of UV rays, prevents dehydration.

The introduction of a 25% alcoholic extract of royal jelly into the composition of the ointment in an amount of 20 wt. % in combination with a 10% alcoholic extract of propolis in an amount of 5 wt. % increases the antimicrobial activity of the ointment, stimulates the processes of tissue regeneration, promotes the manifestation of anti-inflammatory, reparative and antiviral action and a prolonged effect of the dosage form.

In addition to the manifestation of known properties, each component of the claimed composition, in aggregate, enhances its effect, which is evidently explained by the effect of their synergism.

As a result of experimental studies, it was found that the emulsion base provides reliable fixation of the drug on the mucous surface when applied in a thin continuous layer, promotes distribution in the ointment base, the emulsion base increases the bioavailability of royal jelly and propolis due to surface-active properties. Giving the drug the form of an ointment provides convenience and hygiene of use, the drug forms a creeping film, has a pronounced prolonged action and stability during storage.

The proposed ointment is used as follows.

Example 1

The composition of the ointment, wt. %: 25% alcoholic extract of royal jelly - 20.0; 10% alcoholic extract of propolis - 5.0; coconut oil - 20.0; Cremophor RH40 1.0; lutrol F-127 - 20.0; emulsion wax - 2.0; purified water up to 100.0. Get the ointment as follows.

Cremophor, lutrol, emulsion wax and coconut oil are fused. The mixture is thoroughly mixed, homogenized and purified water is added, stirred with a stirrer. In the resulting ointment base add 25% alcoholic extract of royal jelly and 10% alcoholic extract of propolis. The resulting ointment is uniform, yellow, of satisfactory consistency, easily spreads on the skin surface, stable, density - 1.45 g / cm ³ , ointment pH - 6.3. The ointment is easily applied to the skin and mucous membranes with the formation of an even continuous smear, has a pronounced prolonged action, as well as convenience and hygiene of use due to the proposed composition of ingredients.

An alcoholic extract of 25% royal jelly is prepared at a ratio, wt. %: royal jelly 25.0; ethyl alcohol 40% to 100.0.

An alcoholic extract of 10% propolis is prepared at a ratio, wt. %: propolis 10.0; ethyl alcohol 40% to 100.0.

Example 2

The composition of the ointment, wt. %: 25% alcoholic extract of royal jelly - 20.0; 10% alcoholic extract of propolis - 5.0; shea butter - 20.0; Cremophor RH40 1.0; lutrol F-127 - 20.0; emulsion wax - 2.0; purified water up to 100.0.

Get the ointment as follows.

Cremophor, lutrol, emulsion wax and shea butter are fused. The mixture is thoroughly mixed, homogenized and purified water is added, stirred with a stirrer. In the resulting ointment base add 25% alcoholic extract of royal jelly and 10% alcoholic extract of propolis. The resulting ointment is uniform, yellow, of satisfactory consistency, easily spreads on the skin surface, stable, density - 1.45 g / cm ³ , ointment pH - 6.3. The ointment is easily applied to the skin and mucous membranes with the formation of an even continuous smear, has a pronounced prolonged action, as well as convenience and hygiene of use due to the proposed composition of ingredients.

Example 3

The composition of the ointment, wt. %: 25% alcoholic extract of royal jelly - 20.0; 10% alcoholic extract of propolis - 5.0; Cremophor RH40 1.0; lutrol F-127 - 20.0; emulsion wax - 2.0; purified water up to 100.0.

Get the ointment as follows.

Cremophor, lutrol, emulsion wax are fused. The mixture is thoroughly mixed, homogenized and purified water is added, stirred with a stirrer. In the resulting ointment base add 25% alcoholic extract of royal jelly and 10% alcoholic extract of propolis. The resulting ointment is homogeneous, yellow, of satisfactory consistency, easily spreads on the skin surface, stable, density - 1.55 g / cm ³ , ointment pH - 6.3. The ointment is easily applied to the skin and mucous membranes with the formation of a smear, while leaving a sticky film on the skin.

Determination of the antibacterial activity of the ointment according to examples 1-2, containing 25% alcoholic extract of royal jelly and 10% alcoholic extract of propolis, was carried out in accordance with the requirements for dosage forms. Studies of the antibacterial efficacy of the ointment were carried out according to the method described in the GF XII ed., OFS 42-0068-07 (Table 1).

As shown in figure 1, in the model system, in which the reactions of ROS formation took place, the addition of drugs: 25% alcoholic royal jelly extract, 3-10% alcoholic propolis extract at a final concentration of 1 mg / ml, truly suppressed the characteristics of CL. The maximum antioxidant activity (AOA) in this concept was shown by the 2nd sample - 10% alcoholic propolis extract, which reduced the light sum of the luminescence by 92%. 3rd sample - 25% alcohol extract of royal jelly reduced the light sum of luminescence by 69%.

The data obtained indicate that the antioxidant activity of alcoholic extracts from the studied bases had a pronounced character. A less pronounced character was noted in the alcoholic extract from the ointment base No. 2, and more pronounced properties were in the alcoholic extract from the ointment base No. 1. According to table 2 and figure 3, aqueous extracts from ointment base # 1 have AOA.

In a comparative analysis, alcoholic and alcohol-water extracts of the investigated extracts of propolis and royal jelly were investigated (table 3).

The proposed dosage form - an ointment containing beekeeping products royal jelly and propolis, is easy to use and has a wide range of applications in the complex treatment of infectious and inflammatory diseases of the skin and mucous membranes.

Claims (2)

Antibacterial agent for skin and mucous membranes in the form of an ointment containing 10% alcoholic extract of propolis in an amount of 5.0 wt. % as an active ingredient and an ointment base including Cremophor RH40, lutrol F and purified water, characterized in that it additionally contains 25% alcoholic extract of royal jelly as an active substance, additionally contains coconut oil or shea butter as an ointment base and emulsion wax, and as lutrol contains lutrol F-127 with the following ratio of starting components, wt. %: 25% alcoholic extract of royal jelly 20.0 10% alcoholic extract of propolis 5.0 coconut oil or shea butter 20.0 Cremophor RH40 1.0 lutrol F-127 20.0 emulsion wax 2.0 purified water up to 100.0

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