RU2189809C2 - Ointment containing 5% of sainfoin milk vetch dry extract - Google Patents

Abstract

FIELD: pharmaceutical industry, veterinary science, phytotherapy. SUBSTANCE: invention proposes an ointment comprising components taken in the definite ratios, namely: methylcellulose (MC) (carboxymethylcellulose-Na; CMC), glycerol, sainfoin milk vetch dry extract and purified water. The invention provides the enhancement of penetrating ability of an active component into biotissue and tissue healing and the retention of biologically active properties for 2 years. The invention provides the anti-inflammatory, wound-healing and antibacterial effects. EFFECT: simplified composition of ointment, simplified technology of preparing, enhanced biological activity. 1 dwg, 3 tbl

Description

 The invention relates to the pharmaceutical industry and veterinary medicine and provides anti-inflammatory, wound healing and bactericidal action. It has a wide spectrum of action - it is used to treat skin diseases, wounds, ulcers, abrasions.

Known ointment for the treatment of trophic ulcers (AS USSR 305549, class A 61 K 9/06, bull. 36, 1979) containing components in the following ratio, wt. %:
Camphor dextrorotatory - 2.0-4.0
Ethyl ether - 8.0-10.0
Basic bismuth nitrate - 4.0-6.0
Salicylic acid - 1.0-3.0
Amidochloride mercury - 2.0-6.0
Vaseline oil - 8.0-10.0
Medical Vaseline - 43.0-35.0
Lanolin water - 24.0-26.0
The ointment is stored in a glass or porcelain dish at a temperature of 8-10 ^o C; the ointment retains its properties for 6 months, has good smear and adhesion to integumentary tissues and is difficult to wash off with soap.

 However, the presence of bismuth nitrite and amidochloride mercury in the composition can cause a negative effect on skin regeneration, and various people with prolonged use may experience not only an allergic reaction, but also poisoning of the body. As a result, the healing process itself may be ineffective.

Known drug (US Pat. RF 2007164, class A 61 K 9/06, bull. 3, 1994), containing components in the following ratio, wt.%:
Apricot oil - 20.0-82.0
Dibenzoid (DB) - 1.0-7.0
Dibenzoid Peroxide (PB) - 1.0-7.0
Lanolin - 63.9-62.0
Urotropin - 0.05-0.1
Ethanol - 1.0-9.5
This ointment is used in the treatment of skin diseases, burns, in oncology and proctology and has antitumor, antifungal and antiviral activity and retains it for 1 year.

 However, this ointment in its composition contains a large number of chemical components that can cause an allergic reaction of the body and irritation of the wound surface.

Known antiseptic ointment (US Pat. USSR 1805952, class A 61 K 9/06, bull. 12, 1993), containing components in the following ratio, wt.%:
Beeswax - 12.0-13.0
15% rivanol solution - 1.2-1.3
Vegetable Oil - Else
In contrast to the analogs given, this ointment contains chemical components in a smaller amount and due to the content of its wax-oil mixture, it provides increased penetration into biological tissues and tissue healing. The ointment is used for external use in purulent wounds and frostbite. The prepared ointment is suitable for more than 90 days when stored in the dark at room temperature.

 However, the combination of vegetable oil and beeswax does not provide a sufficient active regenerative effect, and the presence of rivanol, although in small quantities, does not exclude the occurrence of an allergic reaction and, on the contrary, with prolonged (more than 14 days) use can cause irritation of the wound surface.

Known ointment for wound healing and anti-inflammatory effects (US Pat. 2128990. Cl. A 61 K 9/06, 35/78, bull. 11, 1999). This ointment has a wide spectrum of action, is used to treat skin diseases, as well as in gynecology and proctology, contains components in the following ratio, wt.%:
Anhydrous lanolin - 15.0-17.0
Interior Fat - 22.0-24.0
Beeswax - 8.0-10.0
Karofilen - 1.0-3.0
Water-alcohol extract of the rhizomes of the cervix erect - 1.0-3.0
Water-alcohol hood of Japanese Sophora - 2.0-4.0
Hydroalcoholic extract of yarrow grass - 1.0-3.0
Propolis alcohol extract - 4.0-6.0
Vegetable Oil - Else
As an ointment base, anhydrous lanolin, internal fat and vegetable oil are included in this preparation. However, the negative side of this ointment is high viscosity, stickiness, unpleasant odor, as well as the allergic reactions manifested due to the content of lanolin.

 Vegetable oils have low chemical stability. When fat is oxidized in hydrolysis, peroxide compounds, aldehydes and other products are formed, which causes allergic reactions, and the wound suture is irritated.

 The combination of vegetable oil and beeswax does not provide a sufficiently active regenerative effect.

 The invention provides increased penetration in biological tissue and tissue healing while maintaining biologically active properties for at least 2 years. The ointment is simple in composition and preparation technology, has a high biological activity. The basis of the invention is the task of creating an ointment that would have increased healing, bactericidal, anti-inflammatory, biologically active and regenerating properties, could be used for skin diseases, injuries, bruises, for the treatment of skin diseases and mucous membranes and would retain its properties for at least 2 years at room temperature, due to the presence in the composition of components of plant origin, and among them components that exclude the decomposition of the structure of the ointment.

 The solution to this problem is ensured by the fact that the ointment with a 5% content of sainfoin astragalus contains MC, glycerin, distilled water, to prevent microbial contamination, benzoic acid, nipagin, nipazole and other antimicrobial excipients that are approved for use are additionally introduced (GF-X1 , 1991).

 It was found that the MC and NaKMH gels, unlike lipophilic bases, have high osmotic activity, and therefore contribute to the rejection of necrotic masses, clean the wound, absorbing wound discharge from purulent wounds.

 Dry extract of Astragalus sainfoin contains flavonoids 30-35%, saponins 40-50%, phenolcarboxylic acids 15-20%, coumarins 0.3-0.5%, tannins 5-10%. The biologically active substances contained in the dry extract of astragalus provide anti-inflammatory, wound healing, antimicrobial action, the presence of flavonoids and phenolcarboxylic acids provides an anti-allergic effect of the ointment. The dry extract is soluble in water.

MC - soluble methyl cellulose (Methylcellulosum solubili) [C ₆ H ₇ O ₂ {OH} _3- x {OCH ₃ } ₃ ] _n . It is an ether of cellulose and methinol, odorless and tasteless. Aqueous solutions of MCs have a high sorption, emulsifying and wetting ability; they form a film upon drying. 3-8% aqueous solutions sometimes with the addition of glycerol form glycerogels, which are used as a non-drying base for ointments (Kondratyeva T.S. et al., 1991).

Glycerin (Glycerinum) C ₃ H ₅ (OH) - a colorless, syrup-forming liquid, sweet taste, odorless with a relative density of 1,224-1,235. In all ratios it mixes with water (Kondratyeva et al., 1991; Muravyov, 1980).

The composition of the ointment with a 5% extract of Astragalus sainfoin, wt.%:
MC - 5.0-7.0
Glycerin - 10.0-12.0
dry extract from the aerial part of astragalus sainfoin - 5.0
Purified water - Up to 100
When the content of the dry extract is less than 5%, the activity of the ointment will be reduced. An extract content of more than 5% does not lead to an improvement in the biological activity of the ointment. The distilled water content is determined by the total content of the components in the ointment.

In a reactor with a steam jacket and an anchor stirrer, 7 kg of MC are loaded and half-filled with water heated to 80-90 ^o C; heating off. The remaining water _^1/2 in the auxiliary reactor dissolved dry extract of astragalus and stirred. After cooling the water, glycerin is added to the main digester and mixed, and then the dry extractor solution is transferred from the auxiliary reactor to the digester and mixed with an anchor stirrer.

 Pharmacological studies of the ointment were carried out on white rats, animals (cats, dogs, cattle).

 An ointment with a 5% dry extract of Astragalus sainfoin has a high pharmacological activity, has a healing, anti-inflammatory, bactericidal effect, cleanses the wound well, rejects necrotic tissue, absorbing the wound compartment, quickly relieves pain, swelling, and stimulates rapid healing of wounds. It is used to treat varicose veins, a number of skin diseases, allergic manifestations.

 An experimental study of the wound healing effect of ointment Astragalus.

 The experiments were carried out on white outbred male rats weighing 150-180 g. Linear skin wounds were inflicted under ether anesthesia. The skin of the back was cut to its own fascia. The length of the incision was 5 cm. Then at an equal distance 3 sutures were put together, bringing together the edges of the wound [1].

 Ointment "Astragalus" was applied to the wound daily 2 times for 8 days. Comparison drug was Solcoseryl ointment, which was applied to wounds in a similar manner. The third group of animals was not treated (control). Evaluation of the wound healing effect was carried out by the method of tensinometry.

 On the 8th day after the operation, the animals (8 in each group) were anesthetized with sodium ethamine (20 mg / kg) and cut out pieces of skin 1 cm wide, 3 cm long, fixed at one end at the upper point using a special clamp, and to the lower end of the piece they suspended another clamp with a platform for installing weights, the mass of which was gradually increased until a scar was fractured (see drawing). The large mass required to rupture the scar indicated its greater strength.

 The experiments showed that in groups of animals treated with Astragalus and Solcoseryl, by the 8th day after the operation, there was a complete rejection of the crusts. In the course of the wound, a formed scar was visible. In the control group, crust rejection was observed in only one case out of 8.

 When tensometric measurement of scar strength obtained the following results. In the group of animals treated with Astragalum ointment, the weight of the weights leading to rupture of the scar was 452.0 ± 42.2 g; receiving ointment "Solcoseryl" 407.2 ± 67.2 g (see table 1).

 Thus, Astragalus and Solcoseryl ointments statistically significantly increase the strength of the scar with respect to the control; accordingly, Astragalus showed a greater tendency in the wound healing action by 1.11 times than solcoseryl.

Study of the anti-inflammatory effect of a 5% ointment with hydrophilic sainfoin astragalus extract (Astragalus)
The anti-inflammatory effect of Astragalum ointment was studied on a model of rat paw edema caused by kaolin. A kaolin suspension was administered under the aponeurosis of the plantar surface of the paw. The dynamics of the increase in edema was measured by the method of oncometry. The paw volume was recorded 1, 2, 3, and 24 hours after administration of kaolin.

 The ointment was applied to the skin of the legs twice a day, preceding the experiment, and 30 minutes before the introduction of kaolin. As a comparison drug, 5% butadione ointment was used, which was applied in the comparison group according to a similar scheme. The experiments showed that the ointment Astragal significantly reduces the degree of swelling of the paws of rats relative to the control at all measurement times (ie, 1, 2, 3, and 24 hours after administration of kaolin). Regarding the group of animals that received Butadion ointment, an unreliable difference was observed only 1 hour after the introduction of kaolin. After 2, 3 and 24 hours, the differences were significant (see table 2). Thus, the ointment containing extracts from astragalus showed a pronounced anti-inflammatory effect on the model of kaolin edema of the paws of rats, superior to that of 5% ointment "Butadion".

The study of the antimicrobial effect of ointment Astragalus
The determination of the sensitivity of pathogenic microorganisms to the ointment Astragalus was carried out using the "wells" method.

 Methodology: A thick layer of agar (PA) in a Petri dish was inoculated with 1-2 ml of suspension of the test microbe. The excess suspension was completely removed, dried for 30 minutes. Then 4-6 holes ("wells") were made with a drill (6 mm in diameter) at a distance of 2.5 cm from the center and at the same distance from each other. Wells were filled with extracts. The cups were left at room temperature for 30 minutes to slightly decrease the level of the drug. Then the cups were placed in a thermostat, without turning over, strictly horizontally to obtain round zones. After 16-18 hours, the diameter of the zones of oppression was measured. Evaluation of the results was carried out according to the diameter of growth inhibition around the disk, including the diameter of the disk itself. The research results are presented in table. 3.

 The larger the delay zone of the test culture, the higher its sensitivity to the Astragalum ointment being tested.

Test cultures:
1. Staphyllococcus aureus 209 r;
2. St. aureus (Makarov);
3. St. aureus Type;
4. St. epidermidis Wood-46;
5. Escherichia coli 675;
6. Shigella flexneri 266;
7. Bacillus subtilis L2;
8. B. Anthracoides-1
From the data table. 3 it follows that the ointment "Astragalus" has an antimicrobial effect.

 Preclinical and clinical studies of the action of Astragalus ointment in veterinary medicine have been carried out.

Literature
1. A.S. USSR 305549, class A 61 K 9/06, bull. 36, 1979.

 2. Pat. USSR 1805952, class A 61 K 9/06, bull. 12, 1993.

 3. Pat. RF 2007164, class A 61 K 9/06, bull. 3, 1994.

 4. Pat. RF 2128990, cl. A 61 K 9/06 35/78, bull. 11, 1999.

 5. The State Pharmacopoeia of the USSR, - 11th ed. - M: Medicine. 1991.- T.2.

 6. Kondratieva TS Technology of dosage forms. -M.: Medicine. 1991 - T. 1.P. 209-210.

 7. Muravyov I. A. Technology of drugs. - M .: Medicine. 1980.- T.2. S. 484-529.

Claims (1)

An ointment with a wound healing, anti-inflammatory, antimicrobial effect, containing extracts from plant materials as the active substance and a base, characterized in that 5% dry extract of astragalus sainfoin is used as plant material, and glycerogel MC (Na CMC) and glycerin are used as the basis in the following ratio of ingredients, wt. %:
MC (Na CMC) - 5.0-7.0
Glycerin - 10.0-12.0
Dry extract from the aerial part of Astragalus sainfoin - 5.0
Purified water - - Up to 100

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