RU2187302C2 - Antiphlogistic wound-healing ointment used for treating the mastitis - Google Patents

Abstract

FIELD: veterinary science. SUBSTANCE: the suggested ointment consists of an ointment foundation, baliz-2 preparation, kumyss peptide fraction at 500-4000 Da molecular weight, pectin, mixture of essential oils, distilled water at the following ratio of components, weight%: ointment foundation 27.5-65.5, baliz-2 20-36.5, kumyss peptide fraction 2-2.5, mixture of essential oils 0.9-1.2, pectin 0.2- 0.3, distilled water - the rest. As essential oils one should use peppermint, eucalyptus, fir, lavender and rose ones. Moreover, it could additionally contain sea buckthorn oil at the quantity of 1.5-2.0 weight%. The ointment enables to shorten the period of wound healing and remove inflammatory processes in case of mastitis. EFFECT: higher efficiency. 4 cl, 4 tbl

Description

 The invention relates to medicine and veterinary medicine, in particular to medicines used as anti-inflammatory, wound healing agents, including in the treatment of mastitis.

 A lot of methods and medicines have been proposed for the treatment of mastitis.

 At present, domestic and foreign industry produces many finished dosage forms, anti-mastitis drugs, the main active ingredients of which are most often various combinations of antibiotics, sulfonamides and nitrofurans. Among them: 1) the introduction intracisternally - mastisany, mastikur, mastitsid, mastaerozol, neomastaerozol, difurol, penersin, mastivalen, endofarm, ITT, neotame, aerodit, sulfatetraretin, supermastikort, ilkoltsellin, tetraolean, yodosan, nitrenol, hlorfilipt, DMSO 90, volatile preparations - onions, garlic, wild garlic, propolis, and other drugs; 2) for intramuscular injection - lactopen; 3) for cutaneous applications - berlitsetin, levomexide, thixotropin, polymer iodismuthsulfamide, vivaton, DMSO-90, DMSO with antibiotics (Rodin I.A., Cow mastitis: etiology, diagnosis and treatment. Krasnodar, Kuban State Agrarian University, 1999, pp. 94-96 )

 Many experts note a number of negative side effects of the use of anti-mastitis drugs containing antibiotics, sulfonamides, nitrofurans, and therefore their therapeutic effectiveness is reduced. Their disadvantages include: a) the formation of drug-resistant strains of opportunistic microbes of mastitis pathogens; b) dysbiosis; c) prolonged excretion of antimicrobial substances with milk, in connection with which milk is not suitable for food purposes; d) toxic effect of nitrofurans; e) one-sided action of drugs; f) with intracisternal administration of drugs, the latter cause additional tissue irritation, and therefore their intravasal and cutaneous application is more promising.

 Known drug containing (wt. H): 2% novocaine 3-4; 10% dimexide 1; 1% diphenhydramine 0.05-0.1; 50% analgin 0.05-0.1; 5% ascorbic acid 0.05-0.1 (Application 97106303/14. The drug for the treatment of mastopathy and method of treatment. Davydkina L.A., 971063202/14, decl. 15.04.97, publ. 20.04.99, B. I. 11, p. 59). It is used in the form of applications for mammary glands, previously fat-free, for 40-60 minutes.

Known means for the prevention and treatment of mastitis in cows, wt.%:
Dioxide - 0.7-1.1
Methyluracil - 0.6-1.0
Diphenhydramine - 0.7-1.1
Fat Regenerating Component - 3.5-6.5
Emulsifier - 1.5-3.5
Distilled water - 80.0-100.0
(Application 96121718/13. Means for the prevention and treatment of mastitis in cows. Sokolov V.D., Sokolov A.V., Andreeva N.L., Voitenko V.D., Tsagaany Volodya, publ. 30.109.96, publ. 02.10.99, B.I. 4, 1999, p. 40).

Known ointment anti-inflammatory and wound healing "Vundekhim", consisting, 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 hood of Japanese Sophora - 2.0-4.0
Hydroalcoholic extract of yarrow grass - 1.0-3.0
Water-alcohol extract of the rhizomes of the cinquefoil - 1.0-3.0
Propolis alcohol extract - 4.0-6.0
Vegetable Oil - Else
(Patent 2128990. The ointment is anti-inflammatory and wound healing "Vundekhim", Chistyakov A. G. Application 98100013/14, decl. 12.01.98, publ. 04.20.99, B.I. 11, p. 318).

Known drug for the treatment and prevention of mastitis in cattle, containing, wt.%:
Ristomycin - 3-5
Lanolin - 20-40
Petroleum jelly - Other
(Patent 2135166. The drug for the treatment and prevention of mastitis in cattle in the dry period. Application 98116801/12, application. 09.09.98, publ. 08.28.99, B.I. 24, p. 187).

Famous ointment - balm "Frolova - for the treatment of burns and infected wounds of various etiologies, consisting, wt.%:
Wax - 10-11
Sea buckthorn oil - 2.4-3.0
Calendula tincture (60-70 ^o ) - 5.0-6.0
Fir oil - 1.0-1.5
Menthol - 0.3-0.4
Olive Oil - Else
(Application 97110475/14, M. cl. (6) A 61 K 9/06, 35/78, Ointment-balm “Frolova.” Frolov V.V., decl. 19.06.97, publ. 20.05.99, B .I. 14, p. 32).

Anti-inflammatory and stimulating granulation of the skin surface ointment, consisting, wt.%:
Dimexide - 5-6
Novocaine - 2-3
Alcohol tincture of calendula - 9-10
St. John's wort alcohol tincture - 9-10
Vinylinum - 7-8
Lanolin - Up to 100
(Patent 2013093, M. cl. (5) A 61 K 435/78, 31/075, 31/00, application 3915735, filed June 26, 85, published May 30, 94, B.I. 10, p. 12 )

The closest of the analogues to the claimed is an ointment for wound healing (Patent 2102062, M. class. (6) A 61 K 9/06, Ointment for wound healing (options), Shurygin A.Ya., Myrinova M.Yu., Zlishcheva EI, application 05.03.94, publ. 01.20.98, 9c.), Containing ointment base, medicinal substances, distilled water. As medicinal substances, it contains the drug baliz-2, the peptide fraction of koumiss with mol. m. 500-4000 Yes. The components are taken in the ratio, wt.%:
Ointment base - 54.0-75.0
The drug baliz-2 - 20.0-36.5
Peptide fraction of koumiss with mol. m. 500-4000 Yes - 2.0-2.5
Distilled Water - Else
In addition, the ointment may contain pectin, which has a gel-forming property and the ability to absorb toxic substances.

 The disadvantages of the ointment include a relatively long period of wound healing and removal of inflammatory processes.

 The technical task of the invention is to reduce the healing time of wounds, removal of inflammatory processes, expanding the arsenal of funds for treating wounds, inflammatory processes, for example mastitis, with the availability of the starting components and their low cost.

To solve the technical problem, an ointment is used, consisting of an ointment base, a baliz-2 preparation, a peptide fraction of koumiss (SK) with a mol. m. 500-4000 Yes, pectin, ether concentrate, distilled water in the following ratio of components, wt.%:
Ointment base - 27.5-65.5
Baliz-2 - 24.0-26.5
Peptide fraction of koumiss with mol. m. 500-400 Yes - 2.0-2.5
Pectin - 0.2-0.3
Essential Concentrate - 0.9-1.2
Distilled Water - Else
Or apply an ointment consisting of an ointment base, a baliz-2 preparation, a peptide fraction of koumiss with a mol. m. 500-4000 Yes, pectin, essential concentrate, sea buckthorn oil, distilled water in the following ratio, wt.%:
Ointment base - 27.5-65.5
Baliz-2 - 24.0-26.5
Peptide fraction of koumiss with mol. m. 500-400 Yes - 2.0-2.5
Pectin - 0.2-0.3
Essential Concentrate - 0.9-1.2
Sea buckthorn oil - 1.5 - 2.0
Distilled Water - Else
An essential concentrate is a mixture of essential oils. Peppermint oil, eucalyptus oil, fir oil, lavender oil and others with anti-inflammatory, antiseptic and other useful properties are used as essential oils of the essential concentrate.

 As ingredients of ointments can be used, for example, emulsifier T-2, petroleum jelly, lanolin, spermaceti, confectionery fat, salad oil "Kuban" and others, which are approved for use in medicine (GF USSR X edition, M., 1968, GF USSR XI edition, 2 volume, M., 1989) and veterinary medicine (Veterinary legislation, 1973, v. 2), taken in various combinations and ratios.

 Peptide fraction of koumiss with mol. m. 500-4000 Yes (SC) has an immunostimulating effect (A.S. USSR 1295557. A method of producing a peptide fraction of koumiss with an immunostimulating effect. Shurygin A.Ya., Zlishcheva E.I., Senicheva M.A., etc. M., CL A 61 K 37/02, publ. 1989). Previous toxicological studies have shown that SC is practically non-toxic, LD-50 is not installed, does not have a cumulative effect, does not have a skin-resorptive effect, does not have a mutagenic effect (Shurygin A.Ya., Zlishcheva E.I. et al. Use of lactic microorganisms and products of their metabolism. Krasnodar, 1996, 286 c).

 Baliz-2 is approved for clinical use as an external agent by order of the Ministry of Health of the USSR 129 of 02.02.1985. The drug has an antibacterial effect (Shurygin A. Ya., Zubarev R.P., Zlishcheva L.I., Use of the drug baliz in clinical practice - Method, recom. M., 1986) and antioxidant effect (Shurygin A.Ya., Yugay G.A., Kolendo S.V., Derbenev A.V. Determination of antioxidant activity of comenic and meconic acids. - Dep. At VINITI 1814-B98, 06.17.98).

 Pectin is approved for use as a preventative agent as an adsorbent of toxic substances (Guidelines for the use of pectins and pectin-containing products for therapeutic and preventive purposes. Kiev, 1990, p. 5).

 Peppermint oil is an easily moving, transparent liquid, colorless or slightly colored yellowish, with a characteristic mint smell and a burning cooling taste without bitterness.

The main components:
L-menthol, L-menton and menthol esters with acetic, valerianic and other acids (GF USSR X ed., M., 1968, p. 488).

 According to V. Petkov ("Modern Herbal Medicine"; Sofia, 1988, p. 197), peppermint oil contains up to 60% menthol and also menthol, methyl acetate, tannin and bitterness.

 Menthol has a local anesthetic spasmolytic effect. When applied topically, it cools tissues and causes a vasoconstrictor effect on peripheral vessels. There is evidence of the antiseptic effect of peppermint essential oil (P. Ikonomov, “Medicinal plants,” Sofia, 1974).

 Eucalyptus oil - an easily moving transparent liquid, colorless or slightly colored in a yellowish color, with a characteristic smell of cineole, without the smell of turpentine.

 The main components: cineole, d, α-pinene, pinocarveol, sexwerpene alcohols - eudesmole and globulol, as well as sexwerpene hydrocarbons and aldehydes (GF USSR X ed., M., 1968, p. 486).

 According to V. Petkov ("Modern herbal medicine", Sofia, 1988, p. 214), eucalyptus oil contains cineol (eucalyptol) - 60-85%, camphene, fenhene, pinocarveol and other substances.

 Eucalyptus oil has anti-inflammatory, antimicrobial and antiviral effects.

 Fir oil light-moving transparent liquid from light yellow to green.

 The main components: boron acetate at least 33%, borneol, camphene (10-12%) (GOST 13-221-86, GF USSR USSR, p. 366).

 Fir oil has antimicrobial activity, biogenostimulating properties, accelerates the regeneration of wound surfaces (Minaeva V.G. Medicinal plants of Siberia. Novosibirsk, Nauka, 1970, p. 36).

 Sea buckthorn oil is an easily moving liquid, painted in a dark orange color with a brownish tint with a characteristic odor (FS 42-1730-95).

 The main components: α-tocopherol, carotenoids, glycerides of oleic, linoleic, palmetic acids and sterols, to which the highest activity is attributed (Minaeva V.G., Medicinal plants of Siberia, Novosibirsk, 1970, p. 84).

 Sea-buckthorn oil has an epithelizing, granulating and anesthetic effect when applied topically (G. Sviridonov. Useful plants of the Altai Mountains - Gorno-Altai Branch of the Book Publishing House, 1978, pp. 83-84).

To obtain the ointment in a sterile mortar at a temperature of 50-60 ^o C, the components of the fat base were mixed, balis-2 was added, thoroughly triturated, then solutions of SC and pectin in distilled water were added, thoroughly triturated until the resulting mass was cooled to a temperature of 30 ^o C. In conclusion peppermint and eucalyptus essential oils were added separately or together, depending on the preparation of the ointment, or other essential oils and sea buckthorn oil. At a mixer speed of 1500 in 1 minute, the mixture was homogenized.

 In this way, ointments were prepared, the compositions of which are given in table 1.

 When preparing the ointments, it was taken into account that in the prototype the ratios of the ointment base, the drug baliz-2, SK, pectin were worked out. In addition, the ratio of the components of the ointment base was taken into account. Within the found limits of the components, searches were going on for the best new ointments.

 The obtained samples were tested for uniformity and storage stability, in addition, the melting temperature, their consistency and slippage were taken into account.

 To determine the uniformity of the ointment, 4 samples (0.02-0.03 g) of the paste were taken from each sample, and 2 samples were placed on a glass slide. They were covered with a second glass slide and tightly pressed until spots with a diameter of about 2 cm were formed. When stains were examined with the naked eye in accordance with the requirements of the USSR State Pharmacopoeia (State Pharmacopoeia of the USSR, 1968, p. 720), no particles were visible in three of the four samples. If particles were detected in a larger number of spots, the determination was repeated on eight samples. Samples with the presence of visible particles in no more than two spots were considered homogeneous.

 When studying storage stability, ointment samples were monitored for 3 days. If during this period of time observed the separation of the aqueous phase, it was believed that the ointment is destroyed.

The optimum melting point was considered to be 36-37 ^o C (human or animal body temperature).

 The consistency and slippery were chosen samples with a soft consistency, sliding, easy to apply.

 The results of the analysis of the samples are shown in table 2.

 As follows from the table. 2, the most satisfying GFK requirements were I-2 ointments; I-3; I-4; II-3, II-4; III-2; III-3; III-4; IV-2; IV-3; IV-4, V-2; V-3; V-4, the wound healing effect of which was checked according to the following method, cartilage wounds with a diameter of 8 mm were applied with a standard stamp in the center of the ears of 85 male chinchilla rabbits weighing 2400-2600 g. (Chernova T.G. Morphological study of experimental wounds under the influence of penetrating radiation in high mountains. Abstract of dissertation for the degree of Doctor of Medical Sciences (Alma-Ata, 1974). A day after the wound was applied and until the end of the experiment, the damaged areas were treated with ointments, taking into account the requirements of GFK and choosing the optimal amount of medicinal substances.

 The wound defects of the animals of the control groups of each series of experiments were smeared with ointment with the same base, but without the addition of essential and sea buckthorn oils, replacing them with an appropriate volume of distilled water. The diameter of the cartilaginous wounds was measured every decade, the results are given in table. 3.

 As follows from the table. 3, the introduction into the ointment of peppermint oil (ointment 1-2, 1-3, 1-4) in a dose of 0.9-1.2 wt. % leads to a reduction in the healing time of wounds by 2-2.5 days, which is 5.63-7.04% compared with the control, the addition of eucalyptus oil accelerates wound healing by 2.3-2.4 days, which is 6, 4-6.7% in relation to the control (ointment II-3, II-4).

 The use of peppermint and eucalyptus oil in a ratio of 1: 2, respectively, made it possible to almost halve the wound healing process (ointment III-2, III-3, III-4), which amounted to 11.8-12.7% compared to control. To expand the spectrum of action of the claimed ointment, sea buckthorn oil was used.

 Testing an ointment with sea buckthorn oil added to the components of the prototype also accelerated the healing process (ointment IV-2, IV-3, IV-4).

 Then, the effectiveness of peppermint, eucalyptus and sea buckthorn oils was determined.

 As can be seen from table 3, the best results were obtained using ointments III-2, III-3, III-4, V-2, V-3, V-4. The term of wound healing in these groups was reduced by 5.4-5.5 days, which amounted to 11.8-15.7% compared with the control.

 The research results showed that the use of the inventive ointment significantly accelerates the time of epithelization, i.e. healing process, without causing complications, as it removes tissue inflammation.

 Thus, the macroscopic state of the wounds, the planimetric analysis of regenerative processes show that the claimed ointment has a wound healing and anti-inflammatory effect.

 The optimal content of peppermint, eucalyptus, sea buckthorn oils should be considered their amount, which is part of the ointments III-2, III-3, III-4, V-2, V-3, V-4, which were selected for further tests.

 With mastitis, a pronounced inflammatory process and a violation of tissue regeneration are observed. The ointment we declare is intended to normalize these phenomena, and it is much more effective than other drugs used for these purposes.

 The experiments were carried out on cows of 5-6 years of age of the Yorkshire breed in the amount of 20 pcs. The presence of mastitis in cows was determined by generally accepted methods (positive test with mastidine, white blood cell count in milk, milk sediment, etc.).

The ointment (III-2, III-3, III-4, V-2, V-3, V-4) was applied to a cleanly washed and non-fatty 50 ^o ethanol udder / Procedures were performed twice a day until the animal was completely recovered.

 The cows of the control group were treated with conventional drugs: mastisan A and B; rifomast. The results obtained showed the high efficiency of the claimed ointment (table 4).

 As can be seen from table 4, the timing of complete recovery of cows compared with the control decreased by 20-33.3%.

 The best results were obtained in the group of animals that used V-3 ointment. The terms of full recovery were reduced by 2 days, which amounted to 33.3% in relation to the control.

 From the above data it is seen that the proposed options for ointments are anti-inflammatory, wound healing and effective in the treatment of mastitis.

Claims (4)

1. An ointment for the treatment of mastitis containing ointment base, baliz-2, peptide fraction of koumiss with mol.m. 500-4000 Yes, pectin and distilled water, characterized in that it further comprises a mixture of essential oils in the following ratio of components, wt.%:
Ointment base - 54.0 - 65.5
Baliz-2 - 20.0 - 36.5
Peptide fraction of koumiss - 2.0 - 2.5
Pectin - 0.2 - 0.3
A mixture of essential oils - 0.9 - 1.2
Distilled Water - Else
2. Ointment according to claim 1, characterized in that it additionally contains sea buckthorn oil in an amount of 1.5-2.0 wt.%.  3. Ointment according to claim 1, characterized in that the mixture of essential oils contains peppermint oil and eucalyptus oil in a ratio of 1: 2.  4. Ointment according to claim 1, characterized in that the mixture of essential oils contains peppermint oil, eucalyptus oil, fir oil, lavender oil in an effective amount.  5. Ointment according to claim 4, characterized in that it additionally contains rose oil in an effective amount.

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