Phenoxymethyl penicillin potassium composition and preparation method and application thereof
By adding gallate and antioxidants as synergists to phenoxymethylpenicillin potassium, a phenoxymethylpenicillin potassium composition was prepared, which solved the problem that the efficacy of penicillin V potassium in treating duck Riemerella vaginalis infection had not been reported, and achieved efficient treatment and cost reduction for duck infectious serositis.
Patent Information
- Application Number
- CN202510797987.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-16
- Publication Date
- 2025-11-07
AI Technical Summary
In the existing technology, there are no reports on the efficacy of penicillin V potassium in treating duck plague Riemerella infection, and drug treatment has the problems of high cost and difficult operation.
A phenoxymethylpenicillin potassium composition was prepared by mixing gallate esters and/or antioxidants as synergists with phenoxymethylpenicillin potassium, for the treatment of duck riberiella infection.
It significantly reduced the minimum inhibitory concentration against Riemerella anatipestifer, improved the prevention and treatment of duck infectious serositis, and reduced drug costs and operational difficulties.
Smart Images
Figure SMS_1 
Figure SMS_2
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of poultry medicine preparation, in particular to a phenoxy methyl penicillin potassium composition and application thereof. BACKGROUND
[0002] Duck Riemerella anatipestifer disease, also known as duck infectious serositis, is a contact infectious disease caused by duck Riemerella anatipestifer, and its characteristic lesions are fibrinous pericarditis, perihelitis, air sacculitis and meningitis. The disease can be transmitted in waterfowl such as ducks and geese, and in chickens and wild birds, and has a high morbidity and mortality. In recent years, chicken-derived duck Riemerella anatipestifer disease has appeared in white-feathered broiler breeding intensive areas in Shandong and Liaoning, showing symptoms of paralysis, three inflammation, and high mortality, causing significant losses to many white-feathered broiler breeding enterprises.
[0003] Currently, the main prevention and control measures for duck Riemerella anatipestifer disease include strengthening feeding management, improving environmental hygiene, vaccination and drug control. Among them, strengthening feeding management and vaccination mainly achieve the effect of preventing and controlling duck Riemerella anatipestifer disease. Strengthening feeding management cannot completely block infection, and infection and death may still occur; vaccination can stimulate chickens and ducks to produce specific immunity, but vaccination increases the cost and workload of breeding enterprises. Drug treatment, as a direct treatment and rapid effect treatment for duck Riemerella anatipestifer disease, can be used for emergency epidemic control and direct treatment, and can also be used for group administration, greatly reducing the operation difficulty of breeding enterprises. Drugs for treating duck Riemerella anatipestifer disease include florfenicol, chloramphenicol, jeimycin, erythromycin, and ampicillin.
[0004] Penicillin V potassium, also known as phenoxy methyl penicillin potassium and 6-phenoxyacetylamino penicillanic acid potassium salt, has a molecular formula of C 16 H 17 KN2O5S and a CAS number of 132-98-9. As a beta-lactam antibiotic, penicillin V potassium mainly inhibits the synthesis of bacterial cell wall mucin, thereby showing a killing effect on sensitive bacteria in the reproductive stage. For example, penicillin V potassium is highly sensitive to pneumococci, staphylococci, streptococci, enterococci, anthrax bacillus and tetanus bacillus, and can be used to treat high chicken coccidiosis, necrotic enteritis and other intestinal diseases of livestock and poultry. However, there is no related report on the use of penicillin V potassium for treating chicken-derived duck Riemerella anatipestifer disease. SUMMARY
[0005] The present application aims at providing a phenoxy methyl penicillin potassium composition and its application. The phenoxy methyl penicillin potassium composition is prepared by mixing phenoxy methyl penicillin potassium and a synergist, which is gallate and / or antioxidant. The phenoxy methyl penicillin potassium composition has high sensitivity to Riemerella anatipestifer and good preventive and therapeutic effect on duck infectious hydropericardium.
[0006] To achieve the above object, the present application adopts the following technical solutions: In the first aspect of the present application, a phenoxy methyl penicillin potassium composition is provided, which is prepared by mixing phenoxy methyl penicillin and a synergist in a mass ratio of 1: (1-10). The synergist is gallate and / or antioxidant.
[0007] Preferably, the gallate is one or more of propyl gallate, butyl gallate or ethyl gallate.
[0008] Preferably, the antioxidant is one or more of 2,6-di-tert-butyl-p-cresol (BHT), butylated hydroxyanisole (BHA) and tert-butylhydroquinone (TBHQ).
[0009] In the second aspect of the present application, the phenoxy methyl penicillin potassium composition is applied in (1) and / or (2) as follows: (1) preparation of a product for preventing or treating Riemerella anatipestifer disease; (2) preparation of a product for inhibiting Riemerella anatipestifer. Riemerella anatipestifer
[0010] In the third aspect of the present application, a product for treating Riemerella anatipestifer disease is provided, which comprises the phenoxy methyl penicillin potassium composition as an active ingredient.
[0011] Preferably, the product for treating Riemerella anatipestifer disease further comprises a solubilizing agent, a dispersing agent, an anti-caking agent and an excipient. The mass ratio of the phenoxy methyl penicillin potassium composition, the solubilizing agent, the dispersing agent, the anti-caking agent and the excipient is (8-12):(15-25):(4-6):(0.2-0.4):(55-75).
[0012] Further preferably, the solubilizing agent is one or more of citric acid, malic acid or potassium phosphate buffer salt, the dispersing agent is sodium tripolyphosphate, the anti-caking agent is silicon dioxide or talc powder, and the excipient is one or more of anhydrous glucose, dextrin, sucrose and fructose.
[0013] Further preferably, the potassium phosphate buffer salt is a mixture of potassium dihydrogen phosphate and dipotassium hydrogen phosphate at a mass ratio of 1: (1.5-2.5).
[0014] As preferred, the dosage form of the product for treating Riemerella anatipestifer disease is a powder.
[0015] In a fourth aspect, the present application provides a preparation method of the product for treating Riemerella anatipestifer disease, comprising the following steps: The dispersant, the anti-caking agent and the excipient are mixed uniformly at a mass ratio to obtain a mixture; then the phenoxy methyl penicillin potassium composition and the cosolvent are added and mixed uniformly to obtain the product for treating Riemerella anatipestifer disease.
[0016] The present application has the following advantages: 1. The present application uses gallic acid ester and / or antioxidant as a synergist to mix with phenoxy methyl penicillin potassium to prepare a phenoxy methyl penicillin potassium composition. The phenoxy methyl penicillin potassium composition has high sensitivity to Riemerella anatipestifer and good prevention and treatment effect on duck infectious serositis.
[0017] 2. The present application can significantly reduce the minimum inhibitory concentration of Riemerella anatipestifer by adding gallic acid ester and / or antioxidant as a synergist in phenoxy methyl penicillin potassium. Specifically, the in vitro MIC experiment shows that the minimum inhibitory concentration (MIC) of phenoxy methyl penicillin alone to Riemerella anatipestifer is 10 μg / mL, and the minimum inhibitory concentration of the phenoxy methyl penicillin composition obtained by mixing phenoxy methyl penicillin and the synergist to Riemerella anatipestifer is 2-5 μg / mL. Riemerella anatipestifer DETAILED DESCRIPTION
[0018] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
[0019] In order to enable those skilled in the art to more clearly understand the technical solutions of the present application, the technical solutions of the present application will be described in detail below with specific examples.
[0020] The experimental materials used in the examples of the present application are all conventional experimental materials in the art and can be purchased through commercial channels.
[0021] In the present application, the strain number of Riemerella anatipestifer is ATCC 11845, the CAS number of propyl gallate is 121-79-9, the CAS number of butyl gallate is 1083-41-6, the CAS number of ethyl gallate is 831-61-8, the CAS number of BHT (butylated hydroxytoluene) is 128-73-0, the CAS number of TBHQ is 1948-33-0, and the CAS number of BHA (butylated hydroxyanisole) is 25013-16-5.
[0022] Example 1: Drug sensitivity test This test sets up 7 treatment groups, respectively: Treatment group 1: Phenoxy methyl penicillin potassium as a drug; Treatment group 2: Phenoxy methyl penicillin potassium and propyl gallate mixed as a drug at a mass ratio of 1:1; Treatment group 3: Phenoxy methyl penicillin potassium and propyl gallate mixed as a drug at a mass ratio of 1:2; Treatment group 4: Phenoxy methyl penicillin potassium and butyl gallate mixed as a drug at a mass ratio of 1:1; Treatment group 5: Phenoxy methyl penicillin potassium and ethyl gallate mixed as a drug at a mass ratio of 1:1; Treatment group 6: Phenoxy methyl penicillin potassium and BHT mixed as a drug at a mass ratio of 1:1; Treatment group 7: Phenoxy methyl penicillin potassium and TBHQ mixed as a drug at a mass ratio of 1:1.
[0023] The drug of each treatment group was dissolved in 1 mL of DMSO (dimethyl sulfoxide) solution, and then 20 mL of sterile water was added, mixed to be clear, to obtain a drug solution; Riemerella anatipestifer was inoculated into a 4% serum-containing trypticase soy broth medium, and cultured at 200 r / min and 37°C for 8 h, the bacterial liquid concentration was adjusted to 1×10 6 cfu / mL, to obtain a Riemerella anatipestifer bacterial liquid.
[0024] The minimum inhibitory concentration (MIC) of the drug in each treatment group on Riemerella anatipestifer was determined by double dilution method. Specifically, 100 mL purified water, 1 g sodium chloride, 1 g peptone and 0.5 g yeast powder were mixed to obtain a liquid culture medium; 5 mL of the corresponding drug solution in each treatment group was added to 5 mL of the liquid culture medium, shaken and mixed, 5 mL of the mixed solution was then added to 5 mL of the liquid culture medium for stepwise dilution, and 100 μL of Riemerella anatipestifer bacterial solution was added to each treatment group. In addition, a positive control group and a negative control group were set up. The positive control group was composed of the liquid culture medium and 100 μL of Riemerella anatipestifer bacterial solution; the negative control group was only composed of the liquid culture medium. Then, each treatment group was cultured at 37°C on a shaking table for 5 h, the results were observed, and the minimum concentration corresponding to the clear well was the minimum inhibitory concentration (μg / mL). The results are shown in Table 1.
[0025] Table 1 Minimum inhibitory concentration of each treatment group The lower the MIC value, the higher the sensitivity of the drug to Riemerella anatipestifer. As can be seen from Table 1, the MIC value of phenoxy methyl penicillin potassium alone on Riemerella anatipestifer is 10 μg / mL, and the MIC value of the phenoxy methyl penicillin potassium composition obtained by adding alkyl gallate / antioxidant as a synergist on the basis of phenoxy methyl penicillin potassium is reduced to 2-3 μg / mL. Therefore, the use of synergists can significantly improve the sensitivity of the finally prepared phenoxy methyl penicillin potassium composition to Riemerella anatipestifer.
[0026] Example 2: Preparation of phenoxy methyl penicillin potassium composition Phenoxy methyl penicillin and propyl gallate were mixed in a mass ratio of 1:1 to obtain the phenoxy methyl penicillin potassium composition.
[0027] Example 3: Preparation of product for treating Riemerella anatipestifer disease Sodium tripolyphosphate, silicon dioxide and dextrin were mixed, and the phenoxy methyl penicillin potassium composition prepared in Example 2 and citric acid were added and uniformly mixed to obtain the product for treating Riemerella anatipestifer disease. The mass ratio of the phenoxy methyl penicillin potassium composition, citric acid, sodium tripolyphosphate, silicon dioxide and dextrin is 10:20:5:0.3:74.7.
[0028] Example 4: Preparation of product for treating Riemerella anatipestifer disease (1) Phenoxy methyl penicillin and propyl gallate were mixed in a mass ratio of 1:1 to obtain the phenoxy methyl penicillin potassium composition; (2) mixing sodium tripolyphosphate, silicon dioxide and glucose, then adding the phenoxy methyl penicillin potassium composition and malic acid, and mixing uniformly to obtain the product for treating duck rimer's bacillus disease; The mass ratio of the phenoxy methyl penicillin potassium composition, malic acid, sodium tripolyphosphate, silicon dioxide and glucose is 8:15:4:0.2:72.8.
[0029] Example 5: Preparation of the product for treating duck rimer's bacillus disease (1) mixing phenoxy methyl penicillin and propyl gallate according to a mass ratio of 1:1 to obtain the phenoxy methyl penicillin potassium composition; (2) mixing sodium tripolyphosphate, silicon dioxide and dextrin, then adding the phenoxy methyl penicillin potassium composition and citric acid, and mixing uniformly to obtain the product for treating duck rimer's bacillus disease; The mass ratio of the phenoxy methyl penicillin potassium composition, citric acid, sodium tripolyphosphate, silicon dioxide and dextrin is 10:20:5:0.3:74.7.
[0030] Test Example 1 Select diseased broilers in a chicken farm in Weifang for testing. The clinical symptoms of the diseased broilers are as follows: the initial stage is mainly respiratory problems, manifested as coughing, and wet cough, and slight snoring; there is a swollen head phenomenon; the spirit is depressed, emaciated, dry claws, closed eyes, neck retraction, fluffed hair, paralysis, and lying down performance is prominent; the leg hock is swollen. The diseased broilers are dissected, and the symptoms are as follows: pericarditis, air sac inflammation, peritonitis, and perihelitis are mainly manifested. The pericardium is covered with a layer of yellow fibrous exudate. The surface of the liver is covered with a layer of white fibrous membrane. The air sac is thickened, and the air sac wall is attached with fibrous exudate. The clinical diagnosis is chicken rimer's bacillus infection.
[0031] Take 31-day-old broilers with duck rimer's bacillus disease, half male and half female, and randomly divide them into 4 groups, 150 in each group. The treatments of each group are as follows: Compound group: the phenoxy methyl penicillin potassium composition prepared in Example 2 is used as the drug; Penicillin V potassium group: phenoxy methyl penicillin potassium is used as the drug; Propyl gallate group: propyl gallate is used as the drug; Positive control group: amoxicillin is used as the drug, which is purchased from Shandong Desin Biological Technology Co., Ltd. The veterinary drug number is 153182859; Negative control group: no drug is given.
[0032] The drug of each treatment group is mixed with water according to the weight ratio of 400g:1t to obtain a drug solution, and the water line is used for drug administration, a total of 5 days of administration, the diseased broilers drink freely, and the daily water consumption of 31-day-old broilers is 0.5kg. Ensure that the feeding management of each treatment group is consistent.
[0033] The clinical observation of a large group of mental state, feces, and autopsy observation of internal organ recovery. The number of deaths, feed intake, average body weight at the beginning of the test, and average body weight at the end of the test are recorded daily during the medication period, and the mortality rate, feed conversion ratio, average daily body weight gain, and average daily feed intake are calculated, as shown in Table 2.
[0034] Among them, the mortality rate = [the number of dead broilers after 5 days of medication / the total number of broilers with medication] x 100%; The feed conversion ratio = the feed intake during the test period / the body weight gain during the test period; The average daily body weight gain = (the weight at the end of the test-the weight at the beginning of the test) / the test days; The average daily feed intake = the total amount of feed consumed during the test period / the total number of animals during the test period.
[0035] Table 2 Mortality rate and other parameters of broilers in each group As can be seen from Table 2, the phenoxy methyl penicillin potassium composition of the present application as a drug can significantly reduce the mortality rate of diseased broilers, increase the feed conversion ratio, and the effect is better than that of amoxicillin treatment.
[0036] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.
Claims
1. A potassium phenoxy methyl penicillin composition, characterized by, The phenoxy methyl penicillin potassium composition is prepared by mixing phenoxy methyl penicillin potassium and synergist in a mass ratio of 1: (1-10); The synergist is gallate and / or antioxidant.
2. The potassium phenoxy methyl penicillin composition as set forth in claim 1, wherein The gallate is one or more of propyl gallate, butyl gallate or ethyl gallate.
3. The phenoxymethylpenicillin potassium composition according to claim 1, characterized in that, The antioxidant is one or more of 2,6-di-tert-butyl-p-cresol, butylated hydroxyanisole and tert-butylhydroquinone.
4. Use of the phenoxy methyl penicillin potassium composition of any one of claims 1-3 in (1) and / or (2): (1) preparing a product for preventing or treating duck Riemerella anatipestifer disease; (2) preparing a product for inhibiting duck Riemerella anatipestifer.
5. A product for treating duck Riemerella anatipestifer disease, the product for treating duck Riemerella anatipestifer disease comprising the phenoxy methyl penicillin potassium composition of any one of claims 1-3 as an active ingredient.
6. A product for use in the treatment of Riemerella anatipestifer disease according to claim 5, wherein, The product for treating duck Riemerella anatipestifer disease further comprises a solubilizing agent, a dispersing agent, an anti-caking agent and an excipient; The mass ratio of the phenoxy methyl penicillin potassium composition, the solubilizing agent, the dispersing agent, the anti-caking agent and the excipient is (8-12):(15-25):(4-6):(0.2-0.4):(55-75).
7. A product for use in the treatment of Riemerella anatipestifer disease according to claim 6, wherein, The solubilizing agent is one or more of citric acid, malic acid or potassium phosphate buffer salt, the dispersing agent is sodium tripolyphosphate, the anti-caking agent is silicon dioxide or talc, and the excipient is one or more of anhydrous glucose, dextrin, sucrose and fructose.
8. A product for the treatment of Riemerella anatipestifer disease according to claim 5, characterized in that, The product for treating duck Riemerella anatipestifer disease is in the form of powder.
9. A process for the manufacture of a product for the treatment of Riemerella anatipestifer disease according to any one of claims 5 to 8, characterized in that, The method comprises the following steps: The dispersing agent, the anti-caking agent and the excipient are mixed in a mass ratio to obtain a mixture; then the phenoxy methyl penicillin potassium composition and the solubilizing agent are added and mixed to obtain the product for treating duck Riemerella anatipestifer disease.