Pharmaceutical composition uberit for treatment of mastitis in cows based on n-tetradecyltributylphosphonium bromide

FIELD: veterinary medicine.

SUBSTANCE: pharmaceutical composition in the form of ointments for treatment of mastitis in cows comprises n-tetradecyltributylphosphonium bromide as active ingredient and petrolatum as an excipient at the ratio of 1:2000.

EFFECT: invention provides a pharmaceutical composition in the form of an ointment, which is new in mechanism of action, effective when applied topically at low therapeutic concentration.

2 ex

 

The invention relates primarily to veterinary medicine and pharmacy, and in particular to means for the treatment of mastitis, which can be used as pharmaceuticals.

Improving the efficiency of treatment of mastitis in cows is a task that is important for ensuring high productivity of dairy cows and milk quality (Vasiliev, Century, Century, the Economic damage from the milk during mastitis in cows. // Veterinary medicine. - 2008. No. 1. - S. 32-34).

For the treatment of mastitis cows offered the use of antimicrobial drugs that are injected vnutrivenno (Sirenko, S. C. Treatment of cows with mastitis. / Sirenko, S. C., Safronov, S. L. // Agrarian Bulletin of the Urals. - 2006. No. 1. - S. 55-56).

There is a method of treatment of mastitis in cows medicinal drug Dipomat, containing in its composition dioxidine (2%), furatsilin (0,04%), beeswax and vaseline oil. In appearance it is a buttery yellow suspension which is produced in bottles of neutral glass 100 ml (20 doses) and the syringes 10 ml (2 doses). Enter intracisternal: if subclinical, serous, catarrhal mastitis in 5 ml of 1 times a day for 3-4 days; if purulent-catarrhal - first injection of 10 ml, then 5 ml with an interval of 24 hours for 5-6 days. Before the introduction of the drug from sick quarters of the udder secret vydavat and teats are disinfected with 70% atelevision. Preparation before applying heat to 36-39°C and shaken, then suck from the bottle with a sterile syringe and injected into the nipple of the affected quarter of the udder by means of a catheter (http://www.veterinar.ru/pharmacy/52/11/). The disadvantage of this method are: high cost, high concentrations of drugs in the drug, the need for special devices for administration of (syringes and dairy catheters), pre-treatment of the nipple ethyl alcohol, and the complexity vnutrivennogo (intracisternal) introduction, which is carried out by expert veterinarians.

There is a method of treatment of mastitis in cows (patent RU 2230571 published 20.06.2004). The method includes vnutriserdechne introduction staphylococcal and streptococcal anatoxins in a mixture with 25% solution of aspirin, at a dose of, respectively, 2 ml and 4 ml Method is highly effective in the treatment of mastitis coccal etiology of cows. The disadvantage of this method is the narrow spectrum of antimicrobial activity (only in respect of coccoid bacteria), while the cause of mastitis are not only streptococci and staphylococci, but also bacteria, coliform bacilli, found Corynebacterium, Mycoplasma, fungi of the genus Candida, Nocardia and others, as well as activators of specific infections (Guidance on the diagnosis, therapy and prevention of mastitis in cows. Min is Alhazred Russia, The Department of veterinary medicine, No. 13-5-2/1948, 30.03.2000, http://www.cap.ru/home/65/aris/bd/vetzac/document/371.html), and expensive due to the high content of dipyrone in pharmaceutical drug and complexity of introducing requiring special devices and participation veterinary specialists.

Closest to the claimed (prototype) is a drug for the treatment of mastitis in animals (patent RU 2200546 published 20.03.2003). The drug is in the form of ointment contains components in the following ratio, wt.%: colloid 1,5-2,0, salicylic acid 1.0 to 1.5, trimekain 0,45-0,55, Hemofarm or levamisole 0,03-0,5, carbon dioxide extract of chamomile 2.0 to 2.5, the juice of celandine 1,5-2,0, dimexide 29,0-33,0, anhydrous lanolin 46,9-47,65 distilled water - the rest. The drug improves the efficiency of treatment. The disadvantage of this drug are mnogonapravlennostj increasing as the cost of the drug, the risk of adverse reactions. So, when using levamisole may cause excitation, increased salivation, increased defecation and urination, ataxia (http://www.vetlek.ru/directions/?id=223). Lanolin may have allergenic and sensitizing effects (Technology of medicinal forms: a Textbook in 2 volumes. Volume 1 / T. S. Kondratyev, L. A. Ivanov, Y. I. Zelikson and others/ edited by T. S. Kondratieva. - M.: Medicine, 1991. - S. 285). When mixed with salts of heavy is yellow (in this example - silver contained in the product "colloid") lanolin its shades, and formed metallic Soaps increase the toxicity of ointments (Reference pharmacist. / Ed. by A. I. Tenzaloy. - M.: Medicine, 1981. - S. 14).

Thus, used drugs have one or more negative properties: high cost, complexity intracisternal introduction did, the activity in relation to a limited range of microorganisms, toxicity. Therefore, the creation of new efficient and easy to use domestic products for the treatment of mastitis in cows is important.

Objective of the claimed technical solution is the creation of effective drug for the treatment of mastitis in cows based on phosphonium salts of simultaneous antibacterial and antimycotic treatment steps, with high penetration and, consequently, low therapeutic doses.

Quaternary phosphonium salts of belong to the III and IV toxicity class - "moderately hazardous" and "toxic" substances, and possess high antibacterial and antimycotic activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis and Candida Albicans [Galkin I. C. Synthesis, structure and study of biological activity of phosphonium salts. / I. Galkina, Turi E. C., Bakhtiyarova Y. C., S. Egorova N., Galkin Century. And.// In the b.: Pharmacology and toxicology of organophosphorus compounds and other biologically active substances. Issue 4: proceedings of the Russian conference dedicated to the 75th anniversary of Professor I. A. Studentswas. - Kazan, 2008. - S. 23]. High antimicrobial, antifungal and antiparasitic activity of salts of Quaternary phosphonium determine the prospects of their application in medicinal forms of local action for treatment of mastitis in cows, in particular n-hexadecyltrimethylammonium bromide with LD502500 mg/kg

The technical result of the claimed invention is the creation of a new mechanism of action of the pharmaceutical composition effective for the treatment of mastitis in cows in the local application in the form of ointment at low (0.05%) of therapeutic concentration.

The claimed technical result is achieved by the use of a composition containing n-tetradecyltrimethylammonium bromide as the active component and the vaseline (excipient) at a ratio of 1:2000.

It is important that the salt of Quaternary phosphonium, in particular, n-tetradecyltrimethylammonium bromide, are stable amphiphilic detergents, interphase catalysts, working both in aqueous and fatty phase and, as a consequence, penetrating agents through biomembranes. As we have shown, Quaternary phosphonium salts of possess high antibacterial properties due to the interaction with the lipid to what components of cell membranes [Galkin, I. C., Melnikova N. B. Turi E. C., Galkin Century. And., Zhiltsov O. E., Zhukova O. C., S. Egorova N. The interaction of phosphonium salts with the lipid components of membranes. / Pharmacy, 2009 - No. 4. - S. 35-38].

Of the investigated prior art is not revealed information about the use of salts of Quaternary phosphonium for the treatment of mastitis in cows, which is proof of the compliance of the claimed technical solution to the criterion "novelty" requirements for inventions.

The active ingredient of the inventive compositions based on salts of Quaternary phosphonium n-tetradecyltrimethylammonium bromide and excipient vaseline in the ratio of 1:2000 used in the claimed technical solution for new purpose - as a drug for the treatment of mastitis in cows, which is obviously not obvious to a person skilled in the analyzed field of technology, thus, the claimed technical solution meets the criterion of "inventive step" requirements for inventions.

The claimed technical solution meets the criterion of "industrial applicability", presented to the invention, since the claimed composition can be obtained by using known components using standard equipment and known methods of pharmaceutical technology.

The essence of the claimed technical the definition of the solution is the creation of a pharmaceutical composition, containing n-tetradecyltrimethylammonium bromide as the active component and petrolatum at a ratio of 1:2000.

The claimed technical solution is as follows:

1. Receive the first component of the claimed composition halide salt of Quaternary phosphonium n-tetradecyltrimethylammonium bromide of General formula (I) by the method described in [Stark H. M. interfacial catalysis. Chemistry, catalysts and application. / Ed. H. M. Starks. M.: Chemistry, 1991. - 157 C.]:

where R1=C4H9C6H5; R2=C12H25With14H29With16H33; Hal=Br

2. Receive pharmaceutical composition through preparation of an ointment composition of 1:2000 of the component of formula I and vaseline.

Advantages of the proposed pharmaceutical composition in the form of ointments is that it is simple in manufacture, use and has therapeutic activity at low concentrations (0.05 per cent), making it a promising drug in veterinary medicine for the treatment of mastitis in cows.

The claimed technical solution is illustrated by the following examples, but is not limited to them.

Example 1. Obtaining a pharmaceutical composition for the treatment of mastitis in cows.

In a porcelain mortar weighed 1 g n-tetradecyltrimethylammonium bromide, pound and mix is with 100 g of vaseline until a homogeneous mass (concentrate). In the capacity maselesele weighed 1900 vaseline, heated to 40°C, stirred and gradually, in small portions when the stirrer type of mortar concentrate. The ointment is stirred for 20 minutes and Packed in glass jars.

Example 2. To study the efficacy of the pharmaceutical compositions of n-tetradecyltrimethylammonium bromide and vaseline (1:2000) for the treatment of mastitis in cows.

Test the effectiveness of the pharmaceutical compositions of n-tetradecyltrimethylammonium bromide and vaseline (1:2000) was performed in the treatment of catarrhal form of mastitis in 5 cows.

Ointment rubbed into the udder 2 times a day, after milking for 5 minutes, combined with massage of the udder.

The results of the study:

Day one: Udder inflamed, red, swollen nipple, painful, touching him cow kick, do not admit to themselves. Milk vydelaetsia with great difficulty. They received milk depending on the type of mastitis watery; contains flakes, or blood clots. Conducted test Trinity mastitis test revealed the presence of mastitis (by the presence of flakes and mucus in the sample of milk in connection with the reagent).

Day two: the Udder is still inflamed, red, swollen nipple, pain in durgiana. Milk vydelaetsia with difficulty, the first stream containing a small amount of flakes.

Day three Udder normal size, the redness is almost absent, nipple less swollen, the pain is negligible. The animal let to itself. Milk vydelaetsia with some difficulty, milk contains a small amount of flakes. Test with Trinity mastitis test shows the presence of mastitis; milk sample still slimy.

Day four: Udder normal size, painless, nipple normal size, blood is missing. Milk vydelaetsia easily and freely. They received milk from the affected quarter is no different from milk from healthy quarters. Test with Trinity mastitis test shows the presence of mastitis; milk sample contains a small amount of mucus.

Day five: Udder normal size, painless, local temperature is not increased, the nipple is normal in size. Milk vydelaetsia easily, they received milk, appearance and texture is no different from milk from healthy quarters. Conducted a test with Trinity mastitis test - mastitis test is negative.

Outcome: full clinical recovery. Consumption of pharmaceutical compositions of n-tetradecyltrimethylammonium bromide and vaseline (1:2000)100 g ointment in the treatment of 1 cow.

Pharmaceutical composition for treatment of mastitis in cows, containingn-tetradecyltrimethylammonium bromide as the active component and vaseline as an excipient in a ratio of 1:2000.



 

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