RU2356556C1 - Medicine for treatment of mammary glands inflammation and traumas in cows - Google Patents

Abstract

FIELD: veterinary.

SUBSTANCE: medication for treatment of mammary glands inflammation and traumas in cows contains as active component ketoprofen, and as base silicon-organic glycerohydrogel with composition: Si(C₃H₇O₃)₄·xC₃H₈O₃·yH₂O, where 3≤x≤10, 20≤y≤40 with dynamic viscosity 4.8-28.5 Pa.s. (20±0.5°C), with component ratio, wt %: ketoprofen 2; silicon-organic glycerohydrogel - the remaining part, medication being prepared by mechanical mixing of components.

EFFECT: invention ensures increase of treatment efficiency.

3 tbl, 3 ex

Description

The invention relates to the field of agricultural production, in particular to veterinary medicine and the treatment of cows with diseases of the udder.

It is known to use Ketofen (10% injection of ketoprofen) in the treatment of cows, in particular for the treatment of acute mastitis, udder swelling, by intravenous or intramuscular injection of the drug (3 mg / kg per day) for at least three days. Soreness of the udder during palpation in animals with mastitis and udder edema disappears from the first day of treatment (see Ketofen's use of a 10% injection solution for treating cows. Merial prospectus, www.merial.ru).

Given the high therapeutic efficacy of Ketophen injection, some of the drawbacks of this method of administration are high doses of injection to create a therapeutic concentration of the drug in the pathological focus at a high price of the imported drug in Russia.

Also known is the drug "Aniksid" for local treatment and prevention of mastitis in cattle (see RF Patent No. 2091070, А61К 33/00, published September 27, 1997. Bull. No. 27). The drug has a wide range of applications - it helps to quickly remove postpartum edema, soften the skin of the nipples, heal wounds and cracks in the nipples, and has an analgesic effect. A certain drawback of such an external preparation is that in its composition, dimethyl sulfoxide (DMSO) is used in an amount that provides transcutaneous conductivity of the active component in an amount of from 5.0 to 30.0 wt.%, Which determines the unpleasant smell of the drug and can cause allergic reactions in personnel using the product to rub the nipples and the udder of the cows into the skin. In addition, DMSO reduces tissue oxygenation and inhibits endogenous respiration.

The objective of the invention is to create a simple composition of a broad spectrum of action for external use in the treatment of mastitis, edema and injuries of the mammary gland in cows, which does not contain toxic drugs like DMSO, but allows the active drug components to pass through the skin into the tissues of the udder and nipples convenient in use and storage, made from the components available in the pharmacopeia, which helps to accelerate the recovery of animals, the preparation of which would not be required with false laboratory equipment and highly qualified specialists, expanding the range of drugs and tools for the effective treatment of diseases of the udder in cows.

The problem is solved by the fact that it is proposed, prepared and clinically tested in laboratory and industrial conditions, an external agent in the form of an ointment, comprising as an active main component the non-steroidal anti-inflammatory drug ketoprofen mixed with organosilicon glycerohydrogel Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ Н ₈ О ₃ · уН ₂ O (where 3≤х≤10, 20≤у≤40) with a dynamic viscosity of 4.8-28.5 Pa · s (20 ± 0.5 ° С) with a ratio of components, wt .%: ketoprofen - 2; organosilicon glycerohydrogel - the rest.

In this case, ketoprofen is used in the form of a 10% injection solution under the brand name Ketofen, and the product is prepared by mechanically mixing the components to a state of a homogeneous, non-stratifying ointment.

The active component of the proposed tool is a non-steroidal anti-inflammatory drug ketoprofen of the carboxylic acid group, a derivative of propionic acid (see Mashkovsky MD Medicines. - 15th ed. M. New Wave, 2008, p. 172).

Unlike the classic NSAIDs previously used that inhibit only the cyclooxygenase pathway, ketoprofen has a double effect, inhibiting both the cyclooxygenase and lipoxygenase pathways. This explains its powerful effect on the vascular and cellular phases of inflammation and a more pronounced analgesic and anti-inflammatory effect compared to other drugs of this pharmacological group. An important advantage of ketoprofen is a marked reduction in the incidence of adverse side effects.

Organosilicon glycerohydrogel is a colorless or slightly yellow substance, odorless, oily, with a wide range of viscosity. In chemical terms, it is an organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40, (2,3-dioxipropyl) - ortho-silicate glycerohydrogel.

Organosilicon glycerohydrogel can be an ointment base for drugs, as it has a set of positive properties:

- non-toxicity (IV hazard class);

- profitability and ease of receipt;

- transcutaneous conductivity of various drugs, large compared with dimethyl sulfoxide;

- anti-inflammatory, decongestant, antioxidant and wound healing activity;

- the ability to protect tissues from drying out and edema, increase their oxygenation;

- storage stability;

- structural compatibility with the lipid component of cell membranes.

The presence of an essential microelement of silicon has an active stimulating effect on the epithelial and connective tissues - it contributes to a more rapid course of reparative processes, improves trophism, and enhances blood circulation. The high transcutaneous activity of organosilicon glycerohydrogel allows you to enhance the effect of the pharmaceutical compositions, reduce their dose and toxicity.

Organosilicon glycerohydrogel of composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40 ((2,3-dioxipropyl) ortho-silicate glycerohydrogel ), developed at the Institute of Organic Synthesis. I.Ya. Postovskogo UB RAS. It is manufactured in accordance with the patent of the Russian Federation No. 2255939, C07F 7/04, published July 10, 05, Bull. No. 19.

In medicine, organosilicon glycerohydrogel mixed with powdered preparations is used in compositions for fixing dentures (Rem. RF Patent No. 2287323, A61K 8/98, 2006) and treatment of periodontitis (RF Patent No. 2296556, A61K 6/02, 2007).

In veterinary medicine, the use of drugs and agents based on organosilicon glycerohydrogel is unknown.

The concentration (2%) of the active substance - ketoprofen - in the proposed tool was determined empirically, taking into account the preparation of a dosage form in the form of an immiscible ointment, easily applied to the udder of cows, and also taking into account its therapeutic effectiveness according to research and testing.

The preparation of pilot batches of the product in the form of an ointment containing 2% ketoprofen based on organosilicon glycerohydrogel was carried out in the laboratory of the Institute of Organic Synthesis named after I.Ya. Postovskogo Ural Branch of the Russian Academy of Sciences as follows: 160 g of organosilicon glycerohydrogel were mechanically thoroughly mixed with 40 ml of Ketofen (10% injection of ketoprofen) until a homogeneous mass was obtained. The obtained 200 g of ointment was distributed in prepared sterile jars with a volume of 50 ml with screw caps and used as intended.

The manufactured product, combining the above-mentioned positive qualities of the base and the active component, when applied to the skin of the affected areas of the udder and nipples evenly distributed in a thin layer. The tool is well and quickly absorbed, provides a pronounced therapeutic effect. Store the product at room temperature in a dry, dark place.

An unobvious effect of the proposed agent for the local treatment of diseases of the mammary gland in cows is that, using only two components: the active one - ketoprofen in the form of a 10% injection solution and the base - organosilicon glycerohydrogel with a transcutaneous and regenerating effect, a highly effective agent is obtained by mechanical mixing external use of a wide spectrum of action, not toxic to the staff, but actively penetrating the tissues of the udder of animals, reducing swelling and accelerating its treatment process, expanding the range of preparations for veterinary medicine, with the additional introduction of organosilicon compounds into the udder tissue, restoring the udder epithelial integument with a simultaneous analgesic effect, which does not require special technical equipment and additional staff training that can be applied to livestock complexes industrial type and in private households.

The novelty of the proposed tool is that the drug ketoprofen in the form of a 10% injection solution is not used parenterally for the new purpose, but as part of the ointment externally as an active component of the drug with a good therapeutic effect and low drug consumption.

The results of the use of an agent containing 2% ketoprofen based on organosilicon glycerohydrogel for the treatment of cows with breast diseases in farms of the Sverdlovsk region are presented below.

Example 1. Cow No. 28624, age 3 years, belonging to the collective farm of Anikiev, Polevskoy, was admitted for treatment on 02.24.07, with closed mechanical damage to the posterior left nipple of the udder and resulting in acute catarrhal mastitis.

In a clinical study of a cow, it was found: temperature - 40.1 ° C, pulse - 92 beats / min, respiration - 34 resp.dv./min. On examination, the injured nipple is swollen, enlarged, a crack in the area of the sphincter; palpation established a dense texture of the nipple tissue, a sharp pain. The left back quarter of the udder (from the side of the injured nipple) is increased in volume, uneven unevenness (foci of densification) in the udder parenchyma, testy consistency, soreness, and an increase in local temperature are revealed upon palpation. Due to the inability to double the secret from the udder, a milk tank catheterized, the obtained secret contains an admixture of blood, clots and casein flakes.

It was prescribed to rub the proposed product (ointment containing 2% ketoprofen based on organosilicon glycerohydrogel) into the skin of the affected nipple and a quarter of the udder once a day.

02/26/07, Temperature - 39.6 ° С, pulse - 74 beats / min, respiration - 24 resp.dv./min. The affected quarter of the udder is sealed. Swelling in the nipple and soreness slightly decreased. Excretion of the secret using a milk catheter. The secret is liquid with an admixture of blood, clots and flakes of casein, its amount has increased.

02/28/07, Temperature - 38.6 ° С, pulse - 68 beats / min, respiration - 18 resp.dv./min. The injured nipple and a quarter of the udder on palpation are soft, elastic, edema subsided, soreness is absent. Milk without any visible changes. The reaction to latent mastitis with a 2% solution of mastidine is negative.

03/01/07, The cow is clinically healthy, transferred to machine milking.

Example 2. Cow No. 15, age 4 years, belonging to the collective farm of Anikiev, Polevskaya, was admitted for treatment on 02.24.07 with post-traumatic edema of the posterior left quarter of the udder.

Temperature - 39.4 ° С, pulse - 74 beats / min, respiration - 25 resp.dv./min. On examination, a quarter of the udder is enlarged in volume, upon palpation, it is compacted, painful. Milk without visible changes, the test with a 2% solution of mastidine is negative. The purpose of rubbing a product containing 2% ketoprofen based on organosilicon glycerohydrogel into the skin of an injured quarter of the udder.

02/25/07, Temperature - 38.4 ° С, pulse - 68 beats / min, respiration - 20 resp.dv / min. On examination, it was found that the edema subsided, a quarter of the udder during palpation was soft, painless.

02/26/07. There are no clinical manifestations of trauma, the use of milk is unlimited.

Example 3. A cow, nicknamed Grazia, age 4 years old, owned by CJSC Sverdlovskoye, was admitted for treatment for non-penetrating wounds of the nipple 03/12/07

Examination of the mammary gland revealed two wounds of the body of the right anterior nipple - 3.5 cm and 2.5 cm long. The nipple is swollen, marked soreness, gaping wounds are noted.

After the debridement, the application of an agent containing 2% ketoprofen based on organosilicon glycerohydrogel was prescribed on the skin of the nipple around the wounds and the adjacent part of the udder twice a day.

03/13/07, the edema of the nipple and the adjacent part of the quarter of the udder decreased, the edges of the wound came closer and were at a distance of 1.5-2 mm, the wound was partially covered with a brownish crust, the wound was scanty.

03/16/07, There is no swelling of the nipple and quarter of the udder, the edges of the wound are brought together to 1-1.5 mm and covered with a dense elastic scab that does not impede milking.

The generalized results of a clinical trial of an agent containing 2% ketoprofen based on organosilicon glycerohydrogel compared to a similar liquid agent based on DMSO (2% solution of ketoprofen on a 50% solution of DMSO) for diseases of the udder and nipples in cows showed certain advantages of the proposed means (tables 1-3).

Table 1 The effectiveness of the use of an agent containing 2% ketoprofen based on organosilicon glycerohydrogel in mastitis in cows Clinical sign The term for normalizing the indicator, days The proposed tool (experience), n = 12 The tool based on DMSO (control), n = 16 Edema 1.92 ± 0.19 3.63 ± 0.18 Lump seal 2.75 ± 0.22 4.00 ± 0.20 Pain reaction 2.00 ± 0.21 3.67 ± 0.16 Reaction with 2% mastidine 5.08 ± 0.19 6.88 ± 0.20 Note: with purulent mastitis, in addition to local exposure, standard therapy was indicated for this disease. table 2 The effectiveness of the use of funds containing 2% ketoprofen based on organosilicon glycerohydrogel for closed injuries of the udder in cows Clinical signs The term for normalizing the indicator, days The proposed tool (experience), n = 6 DMSO-based agent (control), n = 6 Edema 2.42 ± 0.32 4.12 ± 0.36 Tissue Compaction 5.72 ± 0.46 7.28 ± 0.44 Bruising 4.60 ± 0.36 6.12 ± 0.38 Pain reaction 2.68 ± 0.40 3.95 ± 0.40

Table 3 The effectiveness of the use of funds containing 2% ketoprofen based on organosilicon glycerohydrogel for nipple injuries Clinical sign The term for normalizing the indicator, days The proposed tool (experience), n = 12 The tool based on DMSO (control), n = 12 Edema 4.17 ± 0.24 6.33 ± 1.20 Pain reaction 3.48 ± 0.38 6.75 ± 1.42 Wound healing 7.36 ± 1.18 10.88 ± 2.04 Transfer to machine milking 7.88 ± 1.36 10.46 ± 1.84

According to the results of production experiments, it was found that the use of the proposed product in comparison with a liquid product based on DMSO is more convenient, since it is easy to apply and holds well on the skin, is rapidly absorbed, has no specific smell.

When using products based on organosilicon glycerohydrogel, its additional positive effect on the skin of the udder and nipples is noted - the skin becomes soft, elastic, which increases its resistance to trauma in violation of the milking machine.

Clinical trials on animals showed that in groups of animals where the proposed tool was used, the recovery time in the treatment of inflammation and injuries of the breast was shorter by 1.27-1.35 times with respect to the control, which allows us to recommend the drug for widespread use in veterinary medicine, as having anti-inflammatory, emollient effect, maintaining the water balance of the skin and stimulating the regeneration of tissues of the udder of cows.

Claims (2)

1. An agent for treating inflammation and injuries of the mammary gland in cows, including active therapeutic components and a base, characterized in that ketoprofen is used as the active component, and organosilicon glycerohydrogel of the composition: Si (C ₃ H ₇ O ₃ ) ₄ · хС ₃ Н ₈ О ₃ · уН ₂ O, where 3≤х≤10, 20≤у≤40 with a dynamic viscosity of 4.8-28.5 Pa · s (20 ° С ± 0.5 ° С), with the ratio components, wt.%:
ketoprofen 2 organosilicon glycerohydrogel rest,
moreover, the tool is prepared by mechanical mixing of the components. 2. The agent for treating mastitis and breast injury in cows according to claim 1, characterized in that ketoprofen is used in the form of a 10% solution for injection - ketophen.