RU2236229C1 - Antibacterial preparation "risol" for treatment of animals - Google Patents

Abstract

FIELD: veterinary science.

SUBSTANCE: invention can be used for treatment of animals with diseases of bacterial etiology. Preparation comprises rifampicin and antibiotic among series of cephalosporins of the third generation as cefotaxime or ceftriaxone, or cefepime in the following ratio of components, wt.-%: rifampicin, 25.0-75.0; antibiotic among series of cephalosporins of the third generation as cefotaxime or ceftriaxone, or cefepime, 25.0-75.0. Invention provides expanding assortment of antibacterial preparations by the development of the complex preparation with broad of antibacterial effect and high therapeutic effectiveness, prolonged time in retention of therapeutic concentration in body and reducing probability for appearance the resistance to an antibacterial preparation.

EFFECT: valuable antibacterial properties of preparation.

1 tbl, 19 ex

Description

The invention relates to the field of medicine and veterinary medicine and can be used to treat diseases of microbial etiology in animals.

A number of drugs are known from the technical level, including rifampicin as an antibiotic. Rifampicin, an inhibitor of RNA polymerization, is a second-generation antibiotic and has a wide spectrum of antibacterial effects on gram-positive and gram-negative microorganisms, in particular staphylococci, streptococci, meningococci and gonococci. The combination of rifampicin with other active ingredients can significantly increase its therapeutic efficacy.

So we know the combination of rifampicin with plantain juice, used to treat non-specific endobronchitis in patients with destructive pulmonary tuberculosis by intrabronchial administration of a solubilized drug [A.S. 1804854, BI 12, 03/30/93]. As a result of the use of this combination of ingredients, the healing and rehabilitation of caverns is accelerated.

A combination of rifampicin with hydrocortisone is known that is used in the first stage of treatment of coniotuberculosis by endobronchial administration of drugs. The use of rifampicin in the treatment process can relieve the exacerbation of the disease and prevent relapse of the disease in patients with lymphobronchial fistula [A.S. 1777881, BI 4, 11/30/92].

The disadvantage of both combinations is their narrowly specific focus.

The combination of rifampicin with antibiotics expands the spectrum of the drug and multiplies its therapeutic efficacy.

So, the antibacterial drug "Rivicycline" is known, including a combination of rifampicin with tetracycline as antibiotics (Temporary instruction for the use of "Rivicycline". General Veterinary Administration with the State Veterinary Inspection. - M. 07/22/91). The drug has satisfactory therapeutic efficacy due to a qualitative increase in the therapeutic result of the complex compared with the use of each antibiotic separately. The drug is taken orally.

The disadvantages of “Rivicycline” include a high degree of likelihood of resistance to microbial causative agents, associated with the inclusion of tetracycline, which is an antibiotic of the first generation, as well as the oral route of administration in the excipient, which reduces the therapeutic efficacy of the ingredients.

Also known is an antibacterial drug for the treatment of diseases of microbial etiology, in particular gastrointestinal and gynecological, in which rifampicin is combined with polymexin M-sulfate, as well as additives: aubazidan polysaccharide as a stabilizer, nipagin as a preservative, citric acid and sodium hydroxide. The drug is used as a suspension externally [P. RU No. 2103998, BI No. 4, 02/10/99].

The disadvantage of the drug is the complex composition and external use, which reduces the effectiveness of the antibiotic.

The closest analogue to the claimed antibacterial drug in composition and method of use is the antibacterial drug "Dorin", selected as a prototype [P. RU No. 2142804, BI 35, 12.20.99] and containing rifampicin (16.7-83.3%) and doxycycline (83.3-16.7%) as active components. "Dorin" has a wide spectrum of microbial action and therapeutic efficacy against most gram-positive and gram-negative microorganisms, including staphylococci, streptococci, gonococci, etherichia, salmonella, pasteurella, mycoplasmas, Escherichia coli, protozoa.

The drug penetrates well into many tissues and organs. The maximum concentration in the blood is reached 30 minutes after administration.

The drug belongs to the class of low toxic compounds and does not cause functional changes in the body even with a 20-day administration of a multiple therapeutic dose.

All this confirms that the use of rifampicin in combination with doxycycline can significantly increase therapeutic efficacy and reduce the duration of the disease.

Such technical results became possible due to the synergistic action of the constituent ingredients with respect to pathogens of microbial etiology, unattainable in comparison with the action of each ingredient separately and led to a decrease in the effective therapeutic dose. The therapeutic concentration of the antibiotic is maintained in the blood for 24 hours. The drug is used as an injection.

The disadvantage of the drug is a relatively short stay in the body. In addition, precedents for the emergence of resistance to the drug of individual pathogens of microbial etiology are noted.

The objective of the invention is to expand the range of antibacterial drugs by creating a new generation of complex drugs with a wide range of antibacterial effects and high therapeutic efficacy.

Technical results that can be obtained using the invention are:

- increase in therapeutic effectiveness;

- increase the shelf life of the therapeutic concentration of the antibacterial drug in the body;

- reducing the likelihood of resistance to the drug of pathogens of microbial etiology;

- Creation of a new generation antibacterial drug.

The solution of this problem and the achievement of the above results became possible due to the fact that the well-known antibacterial drug consisting of the active ingredients in the form of antibiotics, one of which is rifampicin, contains an antibiotic from the series of cephalosporins as the second antibiotic: either cefotaxime, or ceftriaxone, or cefepin with ratio of ingredients, wt.%:

Rifampicin 75.0-25.0

Antibiotic

cephalosporins third

generations in the form

or cefotaxime, or

ceftriaxone, or cefepine 25.0-75.0

Third-generation cephalosporins are inhibitors of cell wall synthesis, they have a higher activity in Vitro against Enterobacteriacel, favorable pharmacokinetic properties and good penetration into tissues. Cephalosporins show high efficiency against gram-negative bacteria and resistance to the action of β-lactamases produced by them, have a wide spectrum of action; act bactericidal on gram-positive and gram-negative microorganisms, resistant to other antimicrobial agents. Lower efficiency is observed in relation to gram-positive cocci, which is offset by the introduction of rifampicin into the claimed preparation, which is effective against most gram-positive cocci, for example staphylococci, streptococci, meningococci, glucococci.

The invention does not explicitly follow from the prior art and allows to obtain technical results not achievable when using each of the active ingredients individually.

The technical solution has not been identified from the prior art, the combination of features of which is identical to the essential features of the claimed invention.

The claimed antibacterial drug is obtained by mixing pharmacologically pure, active ingredients.

The claimed antibacterial drug "Rizol" was tested with a positive result for respiratory and gastrointestinal diseases of the bacterial etiology of young farm animals. Testing results are presented in examples of specific performance 3-17.

The therapeutic efficacy of “Rizola” is determined by the number of recovered animals (at the time of stabilization of clinical signs) for similar diseases based on the safety of animals, the duration of treatment until the normalized clinical signs, dose and frequency of use are stabilized. The results of monitoring the state of animals are taken into account throughout the entire period until the normalization of clinical signs and within 5 days after stabilization to exclude relapses and complications. The results are statically processed and entered into the table.

Example 1

The diagnosis of bronchial pneumonia.

A group of calves was formed in the amount of 10 goals at the age of 20-60 days with signs characteristic of bronchial pneumonia: shortness of breath, cough, expiration of the serous-mucous character from the nasal openings, in some animals foci of dullness during lung percussion, wheezing, weakening of vesicular breathing and areas bronchial breathing, which is especially well audible in places of blunted percussive sound, an increase in body temperature to 41-42 ° C, a dull and disheveled coat of hair.

The group was treated with the antibacterial drug "Dorin", selected as the closest prototype, with a ratio of active ingredients, wt.%:

Rifampicin 50

Doxycycline 50

Before use, the antibacterial drug is dissolved in water and injected intramuscularly in the lower third of the neck with an interval of 30 hours at a dose of 2 mg / kg of animal weight (the dose selected is close to the minimum therapeutically active dose of "Rizola") until the clinical signs are normalized.

After the second injection, improvement occurs. As a result of treatment, 9 goals recovered, one calf continued to hurt.

The duration of the disease was 5 days.

Therapeutic efficacy is 90.0%.

Example 2

According to example 1.

The group of sick calves includes 15 goals.

The therapeutic dose of Dorin is 3 mg / kg of animal weight. Noticeable improvement was seen after 1 injection.

As a result of treatment, 14 goals recovered, one calf continued to hurt.

The duration of the disease was 3 days.

Therapeutic efficacy of 93.3%.

Example 3 (cefotaxime).

According to example 1.

As an antibacterial drug for injection, Rizol was used with a ratio of ingredients, wt.%:

Rifampicin 75.0

Cefotaxime 25.0,

which corresponds to the limit values of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 2.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the first injection.

The period of the disease was 2 days.

A group of calves - 18 goals. As a result of treatment, 17 goals recovered.

Therapeutic efficacy is 94.4%.

The coat of the recovered animals is even and shiny.

Example 4

According to example 1.

A group of 42 lambs was formed at the age of 2 weeks with signs of bronchial pneumonia. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 25.0

Cefotaxime 75.0,

which corresponds to the minimum value of rifampicin and the maximum cefotaxime within the stated limits, dissolved in water. The therapeutic dose is 2.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the first injection.

The period of the disease was 1.5 days.

As a result of treatment, 40 goals recovered.

The therapeutic efficacy is 95.2%.

The coat of the recovered animals is even and shiny.

Example 5

According to example 1 and 4.

A group of 32 sick lambs was formed. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Cefotaxime 50.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 2.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the first injection.

The period of the disease was 1.5 days.

As a result of treatment, 31 heads recovered.

The therapeutic efficacy is 96.9%.

Example 6

According to example 1 and 4.

The group of sick calves consists of 50 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Cefotaxime 75.0,

which corresponds to the minimum value of rifampicin and the maximum cefotaxime within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the first injection.

The period of the disease was 1.5 days.

As a result of treatment, 48 goals recovered.

The therapeutic efficacy is 96.0%.

Example 7

According to example 1.

The group of sick calves was made up of 10 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 80.0

Cefotaxime 20.0,

which corresponds to rifampicin greater than the maximum and cefotaxime less than the minimum within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the first injection.

The period of the disease was 2.5 days.

As a result of treatment, 9 goals recovered.

The therapeutic efficacy is 90.0%.

Example 8

According to example 1 and 4.

The group of sick calves consists of 15 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 20.0

Cefotaxime 80.0,

which corresponds to a rifampicin content less than the minimum value and cefotaxime more than the maximum value within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Improvement occurs after the second injection.

The period of the disease was 1 day.

As a result of treatment, 14 goals recovered.

The therapeutic efficacy is 93.3%.

Example 9

According to example 1 and 4.

A group of sick calves was formed from 10 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Cefotaxime 50.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 10 goals recovered.

The therapeutic efficacy is 100.0%.

Example 10. (ceftriaxone)

According to example 1 and 4.

A group of sick lambs is formed in the amount of 50 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Ceftriaxone 50.0

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 2.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 49 goals recovered.

Therapeutic efficacy is 98.0%.

Example 11

According to example 1 and 4.

A group of sick calves is formed in the amount of 45 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 25.0

Ceftriaxone 75.0

which corresponds to the average minimum content of rifampicin and maximum ceftriaxone within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 44 heads recovered.

Therapeutic efficacy is 97.7%.

Example 12

According to example 1 and 4.

Formed a group of sick calves with a diagnosis of "Acute-progressing bronchial pneumonia" in the amount of 10 goals. The drug is administered intravenously at a therapeutic dose of 1 mg / kg of animal weight. As an antibacterial drug for intravenous administration, Rizol is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Ceftriaxone 50.0

which corresponds to the average value of the ingredients within the stated limits. The interval between injections of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 10 goals recovered.

The therapeutic efficacy is 100.0%.

Example 13

According to example 1 and 4.

A group of sick lambs is formed in the amount of 50 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 35.0

Cefepin 65.0,

which corresponds to a rifampicin value greater than the minimum and a cefepine value less than the maximum within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 48 goals recovered.

Therapeutic efficacy is 98.0%.

Example 14

According to example 1.

A group of sick calves is formed in the amount of 10 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Ceftriaxone 50.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 10 goals recovered.

The therapeutic efficacy is 100.0%.

In the future, the possibility of treatment with the declared antibacterial drug of gastrointestinal diseases, in particular dyspepsia, characterized by depressed animals, rapid breathing and pulse, the release of liquid feces with gas bubbles, was tested.

Example 15 (cefotaxime).

According to example 1 and 4.

Formed a group of patients with dyspepsia piglets at the age of 2 weeks in the amount of 50 goals. Treatment and control are carried out as in example 1. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Cefotaxime 50.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 4.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 50 goals recovered.

The therapeutic efficacy is 100.0%.

Example 16 (ceftriaxone).

According to example 1 and 17.

Formed a group of patients with dyspepsia of calves in the amount of 10 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 40.0

Ceftriaxone 60.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1 day.

As a result of treatment, 10 goals recovered.

The therapeutic efficacy is 100.0%.

Example 17 (cefepine).

According to examples 1 and 15.

Formed a group of patients with dyspepsia piglets in an acute progressive stage in the amount of 100 goals. As an antibacterial drug for injection, “Rizol” is used with a ratio of ingredients, wt.%:

Rifampicin 50.0

Cefepin 50.0,

which corresponds to the average value of the ingredients within the stated limits, dissolved in water. The therapeutic dose is 2.0 mg / kg of animal weight. The interval of administration of the drug is 30 hours.

Clinical signs were stabilized after the first injection. The second injection is done to consolidate the achieved clinical picture.

The period of the disease was 1.5 days.

As a result of treatment, 49 goals recovered.

The therapeutic efficacy is 97.0%.

Example 18 (rifampicin).

According to example 1.

Formed a group of patients with bronchial pneumonia of calves in the amount of 10 goals. As an antibacterial drug for injection, rifampicin dissolved in novocaine is used.

The therapeutic dose is 3.0 mg / kg animal weight. The interval of administration of the drug is 30 hours. Normalization of clinical signs was achieved after the third injection.

The period of the disease was 3.5 days.

As a result of treatment, 9 goals recovered.

Therapeutic efficacy is 90%.

Example 19 (cefotaxime).

According to examples 1 and 17.

Formed a group of patients with bronchial pneumonia of calves in the amount of 15 goals. As an antibacterial drug for injection, cefotaxime dissolved in water 1 time after 30 hours is used.

The therapeutic dose is 3.0 mg / kg animal weight.

Improvement occurs after the first injection.

The period of the disease was 3 days.

As a result of treatment, 14 goals recovered.

The therapeutic efficacy is 93.3%.

Example 20

According to example 1.

Formed a group of patients with dyspepsia piglets in the amount of 40 goals. The group was treated first with 1 injection of rifampicin dissolved in novocaine, then 1 injection of cefotaxime dissolved in water. The therapeutic dose is 3.0 mg / kg of animal weight with an administration period of 30 hours. By the end of the course of treatment, 38 animals had recovered.

The period of the disease was 2.5 days.

The therapeutic efficacy is 95.0%.

Distinctive features of the claimed invention are the quantitative and qualitative composition, which allows you to create a fundamentally new combined antibacterial drug "Rizol" with popular consumer properties. The drug is soluble in water, relatively well tolerated, does not cause shock when administered intravenously (example 12). The drug is highly effective in the treatment of not only normal respiratory and gastrointestinal diseases having a microbial etiology, but also acutely progressive processes (example 17).

The presence in the claimed preparation of a cephalosporin antibiotic in the form of cefotaxime or ceftriaxone or cefepin allows its composition to be varied depending on the actual clinic of the disease to achieve high therapeutic efficacy and reduce the duration of the disease (examples 9, 10, 12, 13, 14, 15, 16, 17) with the general technical results achieved in connection with the use of any antibiotic from the claimed series of cephalosporins as a part of the preparation, since the indications of the latter for use and the mechanism of action basically coincide give up.

Varying the values of the active ingredients within the stated limits shows the performance of the new antibacterial drug and allows you to choose the optimal limits for the corresponding clinic of the disease (examples 9, 12, 13, 14). Due to the acquired pharmacological properties, the drug is well absorbed, retained for a long time in the body and exhibits a high activity of a wide spectrum (examples 9, 12, 14).

The use of third-generation antibiotics in the claimed preparation eliminates the danger of the manifestation of microorganism resistance to it.

The performance of the drug for the upper and lower values of the active ingredients within the boundary concentrations is shown in the examples (examples 3, 4, 6, 11).

Exceeding or understating the declared boundary values leads to a decrease in therapeutic efficacy and the manifestation of the toxicity of the drug (examples 7 and 8).

The most effective therapeutic dose for the drug "Rizol", as well as for its closest analogue "Dorin", is a dose of 3 mg / kg of animal weight (examples 9, 10, 13, 14, 15, 16). Reducing the dose to 2 mg / kg of the animal’s weight increases the duration of the disease, but nevertheless allows to achieve significant therapeutic efficacy (example 5). An increase in the therapeutic dose to 4 mg / kg of the animal’s weight can slightly reduce the period of illness, but it makes the treatment more stringent and leads to an increase in the cost of treatment and the manifestation of toxicity (example 15).

Thus, the results of the examples obtained by testing the claimed antibacterial drug "Rizol" in domestic animals showed the achievement of positive results: increasing therapeutic efficacy, eliminating the danger of the emergence of resistance of microorganisms to the drug, non-toxicity, reducing the duration of the disease and are provided by a combination of the claimed signs, which allows us to recommend " Rizol "as a new generation drug for the treatment of respiratory and gastrointestinal diseases microbe etiology of both agricultural and domestic animals at a dose of 3 mg / kg of animal weight with an administration period of 30 hours.

Claims (1)

An antibacterial drug consisting of the active ingredients in the form of antibiotics, one of which is rifampicin, characterized in that as the second antibiotic it contains an antibiotic from a series of third-generation cephalosporins in the form of either cefotaxime, or ceftriaxone, or cefepin in the following ratio of ingredients, wt. %: Rifampicin 75.0-25.0 Cephalosporin third antibiotic generations in the form of or cefotaxime, or ceftriaxone or cefepine 25.0-75.0