CN110721160A - Clindamycin sugar-free granules for dogs and cats and preparation method thereof - Google Patents

Abstract

The invention relates to clindamycin sugar-free granules for dogs and cats and a preparation method thereof. The invention overcomes the defect of poor palatability of the existing clindamycin oral drops on the market, and simultaneously meets the requirements of dogs and cats suffering from diabetes and obesity. The clindamycin sugar-free granules prepared by the method have good taste, good solubility, more convenient packaging, storage, transportation and carrying, simple and convenient process and suitability for industrial production.

Description

Clindamycin sugar-free granules for dogs and cats and preparation method thereof

Technical Field

The invention belongs to the technical field of pet medicines, and particularly relates to clindamycin sugar-free granules for dogs and cats and a preparation method thereof.

Background

Clindamycin (Clindamycin), also known as clotrimazole, is a derivative obtained by substituting the hydroxyl group at the 7-position of lincomycin with chlorine. Clindamycin has antibacterial activity against a number of gram-positive aerobic bacteria (excluding enterococci), streptococci (including pneumococci), bacillus (including diphtheria), certain staphylococcal species (including penicillinase-producing strains). It is also active against many anaerobic bacilli, chlamydia, mycoplasma, plasmodium and toxoplasma. The antibacterial mechanism of clindamycin is similar to that of macrolide antibiotics, acts on 50S subunit of bacterial ribosome, inhibits the synthesis of bacterial protein by inhibiting the extension of peptide chain, thereby removing protein A and villous coat on the surface of bacteria, and making the bacteria easy to phagocytize and kill. Clindamycin is also effective in reducing or preventing the formation of proteoglycan-protein complexes, making bacteria less likely to adhere to bone tissue and thus be easily killed by macrophages and antibiotics. In human clinical practice, the traditional Chinese medicine composition is mainly used for abdominal cavity and gynecological infection caused by anaerobic bacteria, joint, soft tissue and bone tissue infection caused by sensitive gram-positive bacteria, septicemia, endocarditis, golden yellow staphylococcus osteomyelitis and the like. In veterinary clinic, the product is mainly used for treating staphylococcus aureus, streptococcicosis, dental infection and osteomyelitis. The clindamycin for pets on the market at present has oral drops, capsules and tablets, and clindamycin hydrochloride is used as a main drug. Capsules and tablets were targeted only to dogs. The target animals of the oral drop are dogs and cats, and the oral drop has poor palatability and poor compliance of dogs and cats due to obvious bitter taste of clindamycin hydrochloride.

Clindamycin phosphate is a semi-synthetic derivative of clindamycin, can be quickly hydrolyzed into clindamycin in vivo to show pharmacological activity, has the action and the application similar to clindamycin hydrochloride, but has less bitter taste than clindamycin hydrochloride, has less toxic and side effect on intestines and stomach by oral administration, has better fat solubility and permeability than clindamycin hydrochloride, is quickly absorbed, has lasting action and higher blood concentration by two times than hydrochloride, and is a broad-spectrum antibiotic with the functions of resisting anaerobic bacteria and aerobic bacteria.

Fructo-Oligosaccharides (FOS), also known as fructooligosaccharides or fructotriose group Oligosaccharides, refer to kestose, nystose and mixtures thereof formed by connecting 1-3 fructose molecules to the fructose residues of sucrose molecules by β -2(1 → 2) -2 glycosidic bonds. The fructo-oligosaccharide is an antibiotic substitute with good stability, safety and environmental protection, is widely added into feed at present, has the main effects of promoting the proliferation of bifidobacterium, improving the defecation speed, reducing the blood nitrogen concentration, promoting the absorption of mineral substances and enhancing the immunity, and has better application value in animal production.

With the increase of the feeding amount of pet dogs and cats, the change of pet food composition and feeding modes, the incidence of diabetes of dogs and cats rises year by year. Among the clinical diagnoses of small animals, diabetes is one of the most common metabolic endocrine diseases of dogs. Mainly in middle and old aged dogs, and the prevalence is increasing year by year. The current incidence of diabetes in dogs is estimated to be 1/66-1/2000 and in cats is estimated to be 1/800. The preparation does not contain sugar which causes the increase of blood sugar such as sucrose, glucose and the like, and has definite clinical curative effect on the complications of aerobic bacteria, anaerobic bacteria and the like caused by diabetes.

Disclosure of Invention

The invention aims to provide clindamycin sugar-free granules for treating skin infection (wound and abscess), deep infection, tooth infection and dog osteomyelitis, which solve the problems of poor palatability and inconvenient transportation and storage of the existing clindamycin oral drops taking clindamycin hydrochloride as a main drug in the market.

The invention also aims to provide a preparation method of the clindamycin sugar-free granules for dogs and cats, which is simple and feasible and is suitable for industrial production.

The third purpose of the invention is to provide the application of fructo-oligosaccharide in preparing medicines for improving the palatability of the medicines. Through tests, the fructo-oligosaccharide can effectively improve the taste of the clindamycin phosphate and relieve the irritation of the medicine to the gastrointestinal tract.

The fourth purpose of the invention is to provide the clindamycin sugar-free granules which are suitable for obese or hyperglycemic dogs and cats, the fructo-oligosaccharide can not be digested and absorbed by stomach and small intestine, the granules have the effects of promoting the proliferation of bifidobacteria, lactobacillus and the like, the gastrointestinal tract function can be improved, the characteristics of preventing the absorption of cholesterol and the increase of blood sugar value can be realized, and the granules can be eaten by dogs and cats suffering from diabetes or being fat in weight.

The invention is realized by the following technical scheme:

the clindamycin sugar-free granule for dogs and cats is prepared from the following raw materials in parts by weight:

the weight ratio of the clindamycin phosphate to the fructo-oligosaccharide is 2: 1-2: 3, and the preferred weight ratio of the fructo-oligosaccharide to the clindamycin phosphate is 1: 1.

The filler is one or more of mannitol, sorbitol and maltitol; the flavoring agent is one or more of beef essence, milk essence and sweet orange essence; the adhesive is one of PVPK30 or hydroxypropyl methylcellulose; the wetting agent is ethanol water solution with a proper proportion.

The clindamycin sugar-free granule for dogs and cats is prepared by the following steps:

(1) taking the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler according to the prescription amount, respectively sieving the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler by a sieve of 80 meshes, and taking undersize materials for later use;

(2) diluting clindamycin phosphate, correctant and fructo-oligosaccharide with filler at multiple ratio, respectively, adding the mixture of clindamycin phosphate and correctant into a dry mixer, mixing for 5min, adding the mixture of fructo-oligosaccharide, and mixing for 30min at a rotation speed of 20-50 r/min;

(3) adding PVPK30 or hydroxypropyl methylcellulose into a proper amount of ethanol water solution to obtain an adhesive, rapidly spraying the adhesive on the total mixture stirred by a granulator for multiple times, granulating by using a 16-mesh screen after the adhesive is tightly held into a conglobation and instant dispersion state, drying at 60 ℃ until the moisture content is less than 3%, and grading by using a 14-mesh screen;

(4) subpackaging to obtain the final product.

The preparation method of the clindamycin sugar-free granules for dogs and cats is characterized in that fructo-oligosaccharide is added to optimize the palatability of the medicine, reduce the stimulation of the medicine to the gastrointestinal tract and improve the compliance of the medicine.

The invention has the beneficial effects that:

1. the invention is the only veterinary preparation taking clindamycin phosphate as a main drug, and fructo-oligosaccharide is added, so that the taste of the clindamycin phosphate can be effectively improved, the palatability is good, the water solubility is good, the preparation can be used by mixing materials and can also be taken after being dissolved in water, and the use is convenient.

2. The product is sugar-free granule, and is suitable for obese or hyperglycemic dogs and cats.

3. The invention has the advantages of convenient packaging, storage, transportation and carrying, simple process and suitability for industrial production.

Detailed Description

Example 1: the prescription composition of 2% (calculated as clindamycin) specification clindamycin phosphate granules is as follows:

example 2: the prescription composition of 30% (calculated as clindamycin) specification clindamycin phosphate granules is as follows:

example 3: the prescription composition of the clindamycin phosphate granules with the specification of 16% (calculated by clindamycin) is as follows:

example 4: the prescription composition of the clindamycin phosphate granules with the specification of 16% (calculated by clindamycin) is as follows:

note: examples 1-4 describe a method for preparing clindamycin sugar-free granules for dogs and cats:

(1) taking the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler according to the prescription amount, respectively sieving the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler by a sieve of 80 meshes, and taking undersize materials for later use;

(2) diluting clindamycin phosphate, correctant and fructo-oligosaccharide with filler at multiple ratio, respectively, adding the mixture of clindamycin phosphate and correctant into a dry mixer, mixing for 5min, adding the mixture of fructo-oligosaccharide, and mixing for 30min at a rotation speed of 20-50 r/min;

(3) adding PVPK30 or hydroxypropyl methylcellulose into a proper amount of ethanol water solution to obtain an adhesive, rapidly spraying the adhesive on the total mixture stirred by a granulator for multiple times, granulating by using a 16-mesh screen after the adhesive is tightly held into a conglobation and instant dispersion state, drying at 60 ℃ until the moisture content is less than 3%, and grading by using a 14-mesh screen;

(4) subpackaging to obtain the final product.

Example 5: safety test

Healthy adult dogs, 30 dogs, weighing about 10 kg/dog, and half male and female, were selected. Feeding animals in room with room temperature of 20 deg.C and humidity of 40% -60%, and freely eating and drinking water. After 2 weeks of feeding, 24 healthy and disease-free dogs, half of which are female and half of which are selected from the dogs, are randomly divided into 4 groups of 6 dogs each, and the weight of each group is basically consistent. The marking is carried out by an ear mark method. The clindamycin granules in example 2 are used as experimental medicines, and according to the clinical recommended administration dose (11mg/kg in clindamycin) of the medicine, the administration doses of each group are 0, 1, 3 and 5 times of the application dose and are fed once every 24 hours. Oral administration for 28 days.

Table 1 experimental design and grouping

Experiment grouping	Dosage to be administered
		Group 1	0 time of medicine dosage
Group 2	1 time of medicine dosage
		Group 3	3 times of the drug dose
Group 4	5 times of medicine dosage

The reaction of each group of test dogs to different doses of drugs including drinking water and food intake conditions, mortality and the like is observed during the experiment, blood is collected before and after the administration, blood biochemical analysis is carried out, the test dogs are subjected to autopsy after the experiment is finished, and histopathological examination is carried out on organs and suspicious tissues which are observed by naked eyes and affected.

The experimental results show that during the whole experimental period, all experimental animals in each experimental group have good health conditions, normal drinking and ingestion and no death records. The average weight gain, the feed conversion ratio, the hematological parameters and the blood biochemical indexes of all groups of test dogs have no obvious difference, the tissues and organs have no obvious abnormality, and the pathological sections have no specific pathological change. The clindamycin phosphate particles of the invention are therefore clinically safe for use on laboratory animal dogs at least 5 times the recommended dose.

Example 6: palatability test

55 dogs and 10 cats in a wandering pet shelter are taken as experimental objects, 6 identical water drinkers are taken, 300ml of drinking water is added into each water drinker, and then medicines are added according to the table 2, wherein the water drinkers I-V are taken as experimental groups, and the addition amount of the medicines is 0.1 percent of clindamycin in the water drinkers; the waterer VI was a blank control group without added medication. All the experimental subjects freely drink water, the drinking conditions of the experimental animals are observed, the amount of water remaining in the drinking fountain after 1 hour is recorded, and the drinking rate is calculated.

TABLE 2 test design

Group of	Drinking machine number	Medicine
			Group 1	Drinking machine I	Example 1 clindamycin sugar-free granules
Group 2	Drinking machine II	Example 2 clindamycin sugar-free granules
			Group 3	Drinking machine III	Example 3 clindamycin sugar-free granules
Group 4	Drinking fountain IV	Example 4 clindamycin sugar-free granules
			Group 5	Drinking machine V	Commercially available clindamycin hydrochloride drops
Group 6	Drinking machine VI	Blank control

TABLE 3 Pet drug Drinking palatability test results

Numbering	Initial amount of water (ml)	Residual water volume (ml)	Percentage of drinking water (%)
				Group 1	300	103	65.7
Group 2	300	92	69.3
				Group 3	300	68	77.3
Group 4	300	46	84.7
				Group 5	300	265	11.7
Group 6	300	169	43.7

The test results are shown in table 3, and it can be seen from the results that the clindamycin sugar-free granules provided by the invention have good palatability and are obviously better than commercially available clindamycin hydrochloride drops and blank control groups, but the formula of example 1 adopts a large proportion of mannitol, the content specification is low, the addition amount is large in clinical use, over-sweetness is caused, and the sweetness is too low due to overlarge specification compared with the formula of example 2, so that the difference between the group 1 and the group 2 is not obvious. The final test result shows that the clindamycin granules with the weight ratio of the fructo-oligosaccharide to the clindamycin phosphate of 1:1 have the best palatability.

Claims (6)

1. The clindamycin sugar-free granule for dogs and cats is characterized by comprising clindamycin phosphate and fructo-oligosaccharide.

2. The clindamycin sugar-free particle for dogs and cats as claimed in claim 1, which is prepared from the following raw materials by weight:

3. the clindamycin sugar-free granule for dogs and cats as claimed in claim 2, wherein the weight ratio of clindamycin phosphate to fructo-oligosaccharide is 2: 1-2: 3.

4. The clindamycin sugar-free granule for dogs and cats as claimed in claim 3, wherein the weight ratio of fructo-oligosaccharide to clindamycin phosphate is 1: 1.

5. The clindamycin sugar-free granule for dogs and cats as claimed in claim 2, wherein the bulking agent is one or more of mannitol, sorbitol, maltitol; the flavoring agent is one or more of beef essence, milk essence and sweet orange essence; the adhesive is one of PVPK30 or hydroxypropyl methylcellulose; the wetting agent is ethanol water solution with a proper proportion.

6. The clindamycin sugar-free granule for dogs and cats as claimed in claim 2, wherein the preparation method comprises the following steps:

(1) taking the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler according to the prescription amount, respectively sieving the clindamycin phosphate, the fructo-oligosaccharide, the flavoring agent, the adhesive and the filler by a sieve of 80 meshes, and taking undersize materials for later use;

(2) diluting clindamycin phosphate, correctant and fructo-oligosaccharide with filler at multiple ratio, respectively, adding the mixture of clindamycin phosphate and correctant into a dry mixer, mixing for 5min, adding the mixture of fructo-oligosaccharide, and mixing for 30min at a rotation speed of 20-50 r/min;

(3) adding PVPK30 or hydroxypropyl methylcellulose into a proper amount of ethanol water solution to obtain an adhesive, rapidly spraying the adhesive on the total mixture stirred by a granulator for multiple times, granulating by using a 16-mesh screen after the adhesive is tightly held into a conglobation and instant dispersion state, drying at 60 ℃ until the moisture content is less than 3%, and grading by using a 14-mesh screen;

(4) subpackaging to obtain the final product.