CN110917140A - Veterinary doxycycline soluble powder medicine and preparation method thereof - Google Patents
Veterinary doxycycline soluble powder medicine and preparation method thereof Download PDFInfo
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- CN110917140A CN110917140A CN201811097110.9A CN201811097110A CN110917140A CN 110917140 A CN110917140 A CN 110917140A CN 201811097110 A CN201811097110 A CN 201811097110A CN 110917140 A CN110917140 A CN 110917140A
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- doxycycline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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Abstract
The invention discloses a veterinary doxycycline soluble powder medicament and a preparation method thereof, belonging to the technical field of veterinary medicaments. The veterinary doxycycline soluble powder medicine comprises the following components: doxycycline, trimethoprim lactate, and anhydrous glucose. The doxycycline, the trimethoprim lactate and the anhydrous glucose are respectively crushed and sieved; weighing the sieved doxycycline and the lactic acid trimethoprim, adding anhydrous glucose with the same weight as the sum of the two components, premixing by a dispersion method, adding the rest of the anhydrous glucose, fully mixing, uniformly mixing, crushing again and sieving to obtain the finished product. The veterinary doxycycline soluble powder has the advantages of good medicament effect, quick response, convenient use, simple and feasible preparation method, low cost, convenience for large-scale industrial production and contribution to popularization and application.
Description
Technical Field
The invention relates to the technical field of veterinary medicines, in particular to a doxycycline soluble powder medicine for livestock and a preparation method thereof.
Background
Doxycycline reversibly binds to a receptor on the 30S subunit of the bacterial ribosome, interferes with the formation of a ribosome complex between tRNA and mRNA, prevents peptide chain elongation to inhibit protein synthesis, and thus rapidly inhibits bacterial growth and reproduction. Doxycycline is a broad-spectrum antibacterial drug, has an inhibiting effect on gram-positive bacteria and gram-negative bacteria, is quickly absorbed by oral administration, is less influenced by food, has high bioavailability, strong tissue permeability, wide distribution, long effective blood concentration maintaining time and a pig in-vivo protein binding rate of 93 percent. Doxycycline also has certain inhibitory action on mycoplasma, eperythrozoonosis, chlamydia, rickettsia and the like.
Doxycycline can be used in the treatment of various animal diseases. Respiratory tract infection: asthma, cough, dyspnea, purple ear tip, general redness, etc. of pig caused by asthma, swine plague, atrophic rhinitis, etc.; nasal cavity caused by poultry acute and chronic respiratory diseases has symptoms of secretion, lacrimation, mouth opening respiration, tracheal rale and the like. Infection of the digestive tract: yellow, gray, dark green or bloody thin feces caused by yellow and white scour of piglets, dysentery of piglets, paratyphoid of piglets, etc.; white rice soup-like thin feces, watery diarrhea or red to black brown coal tar-like feces caused by avian colibacillosis, pullorum disease, paratyphoid fever, fowl cholera, necrotic enteritis, etc. Infection of the sow after delivery: mastitis-metritis-agalactia syndrome, increased body temperature of sow after delivery, lochiorrhea of uterus, red and swollen breasts, hard lumps, reduced or no milk and the like. And (3) the other: abortions of pregnant sows caused by leptospirosis and chlamydia disease, etc.
Animal infectious diseases seriously threaten the health of animals and restrict the development of animal husbandry. The development of the high-efficiency broad-spectrum antibacterial drug has great practical significance.
Disclosure of Invention
In order to solve the technical problems, the invention discloses a veterinary doxycycline soluble powder medicament and a preparation method thereof.
The technical scheme adopted by the invention is as follows: a doxycycline soluble powder medicine for livestock comprises the following components in every 100g of medicine: 9-11g of doxycycline, 1.5-2.5g of trimethoprim lactate and the balance of anhydrous glucose.
Preferably, the veterinary doxycycline soluble powder medicine comprises the following components in every 100g of medicine: 10g of doxycycline, 2g of trimethoprim lactate and the balance of anhydrous glucose.
A method for preparing a doxycycline soluble powder medicament for livestock comprises the following steps:
(1) respectively pulverizing doxycycline, trimethoprim lactate and anhydrous glucose, and sieving;
(2) weighing doxycycline and trimethoprim lactate according to the prescription amount after sieving in the step (1), adding anhydrous glucose with the same amount as the sum of the weights of the two components, premixing for 15 minutes according to a dispersion method, adding the rest of anhydrous glucose, fully mixing for 40 minutes, uniformly mixing, crushing again and sieving to obtain the doxycycline and trimethoprim lactate.
Preferably, in the method for preparing the doxycycline soluble powder medicine for livestock, the mesh number of the crushed and sieved screen is 80 meshes.
The doxycycline is reversibly combined with a receptor on a bacterial ribosome 30S subunit to interfere tRNA and mRNA to form a ribosome complex, so that the peptide chain is prevented from being prolonged to inhibit protein synthesis, the growth and the reproduction of bacteria are rapidly inhibited, and the doxycycline plays a role in stabilizing drug effect by adding the trimethoprim lactate, so that the inhibition effect of the doxycycline on gram positive bacteria and gram negative bacteria is more prominent. The doxycycline soluble powder medicine for livestock has good medicine effect, quick response and convenient use, and the preparation method of the doxycycline soluble powder medicine is simple and easy to implement, has low cost, is convenient for large-scale industrial production and is beneficial to popularization and application.
Detailed Description
The present invention will be described in detail with reference to the following embodiments.
Example 1
A doxycycline soluble powder medicine for livestock comprises the following components in every 100g of medicine: 9g of doxycycline, 1.5g of trimethoprim lactate and the balance of anhydrous glucose.
The preparation method of the doxycycline soluble powder medicine for livestock comprises the following steps:
(1) respectively pulverizing doxycycline, trimethoprim lactate and anhydrous glucose, and sieving;
(2) weighing 9g of doxycycline and 1.5g of trimethoprim lactate sieved in the step (1), adding 10.5g of anhydrous glucose, premixing for 15 minutes according to a dispersion method, adding the rest of anhydrous glucose, fully mixing for 40 minutes, uniformly mixing, crushing again and sieving with a 80-mesh sieve to obtain the doxycycline hydrochloride injection.
Example 2
A doxycycline soluble powder medicine for livestock comprises the following components in every 100g of medicine: 10g of doxycycline, 2g of trimethoprim lactate and the balance of anhydrous glucose.
The preparation method of the doxycycline soluble powder medicine for livestock comprises the following steps:
(1) respectively pulverizing doxycycline, trimethoprim lactate and anhydrous glucose, and sieving;
(2) weighing 10g of doxycycline and 2g of trimethoprim lactate sieved in the step (1), adding 12g of anhydrous glucose, premixing for 15 minutes according to a dispersion method, adding the rest of anhydrous glucose, fully mixing for 40 minutes, uniformly mixing, crushing again and sieving with a 80-mesh sieve to obtain the doxycycline hydrochloride.
Example 3
A doxycycline soluble powder medicine for livestock comprises the following components in every 100g of medicine: doxycycline 11g, trimethoprim lactate 2.5g, and the balance of anhydrous glucose.
The preparation method of the doxycycline soluble powder medicine for livestock comprises the following steps:
(1) respectively pulverizing doxycycline, trimethoprim lactate and anhydrous glucose, and sieving;
(2) weighing 11g of doxycycline and 2.5g of trimethoprim lactate sieved in the step (1), adding 13.5g of anhydrous glucose, premixing for 15 minutes according to a dispersion method, adding the rest of anhydrous glucose, fully mixing for 40 minutes, uniformly mixing, crushing again and sieving with a 80-mesh sieve to obtain the doxycycline hydrochloride.
Test example 1 stability test
The veterinary doxycycline soluble powder medicament prepared in the examples 1 to 3 is subjected to room temperature sample retention observation test, accelerated test, cold storage test and anti-freezing stability test respectively, the stability of the veterinary doxycycline soluble powder medicament is observed, whether unstable phenomena such as discoloration, agglomeration, aging and the like occur or not is confirmed, and the water solubility of the veterinary doxycycline soluble powder medicament is checked.
1. Sample retention observation test at room temperature
The doxycycline soluble powder medicine for livestock of the examples 1 to 3 is taken and placed at room temperature for observation, and the doxycycline concentration is respectively determined at 0d, 30d, 60d, 120d and 180d after the preparation. The observation result shows that the doxycycline soluble powder for livestock has the same appearance as the original product, does not have the conditions of discoloration, agglomeration, aging and the like, and has no obvious change in content, thus the doxycycline soluble powder for livestock has good stability at room temperature.
2. Accelerated test
The doxycycline soluble powder medicine for livestock of the embodiment 1 to 3 is taken and packaged in bags, sealed and then placed in an acceleration box with the temperature of 40 ℃ and the relative humidity of 70 percent for storage for 90 days, and the sampling and observation are carried out every 30 days. The results show that the doxycycline soluble powder for livestock of examples 1-3 has the same appearance as before after heat storage, and has no discoloration, agglomeration, aging and other conditions, and the water solubility is qualified, which indicates that the heat storage stability is good.
3. Cold storage test
The veterinary doxycycline soluble powder medicament prepared in the embodiment 1 to 3 is placed in a refrigerator at 4 ℃ for refrigeration for 180 days, and the observation result shows that the veterinary doxycycline soluble powder medicament has the appearance as before, the conditions of discoloration, agglomeration, aging and the like do not occur, and the water solubility is qualified, so that the veterinary doxycycline soluble powder medicament has good low-temperature stability over time.
4. Stability against freezing
The doxycycline soluble powder medicine for livestock of the examples 1 to 3 is stored in a refrigerator at the temperature of-10 ℃ for 7 days and is restored to the room temperature for observation. The results show that the veterinary doxycycline soluble powder medicament prepared in the embodiments 1 to 3 has the same appearance as the veterinary doxycycline soluble powder medicament prepared in the embodiments, no discoloration, agglomeration, aging and other conditions occur, and the water solubility is qualified through inspection, which indicates that the veterinary doxycycline soluble powder medicament has good freezing resistance stability.
Test example 2 clinical efficacy test
1. Test protocol
Selecting 120 healthy ternary pigs with the weight of 20-25kg, and randomly dividing the pigs into 6 groups: in test 1 group, 20 animals, the doxycycline soluble powder medicine for livestock prepared according to example 1 is dissolved in water, so that the effective concentration of the medicine is 100 mg/ml; experiment 2, 20 animals, the doxycycline soluble powder medicine for animals prepared according to the example 2 is added into water to be dissolved, so that the effective concentration of the medicine is 100 mg/ml; experiment 3, 20 animals, the doxycycline soluble powder medicine for animals prepared according to the example 3 is added into water to be dissolved, so that the effective concentration of the medicine is 100 mg/ml; in 20 positive control groups, doxycycline raw materials are added into water to be dissolved, so that the effective concentration of the medicine is 100 mg/ml; model control group, 20 heads, only toxic challenge and no drug administration; blank control group, 20 heads, no toxicity attacking and no drug administration. 100 pigs, except the blank control group, were injected subcutaneously with Pasteurella multocida.
2. Evaluation index
2.1 clinical symptoms: regularly observing and recording clinical symptoms of the pigs every day, such as mental state, appetite, respiration, cough, nasal secretion and visible mucous membrane color;
2.2 pathological examination: performing a dissection examination on dead pigs, observing pathological changes, and making pathological sections;
2.3 curative effect judgment: cure, improve, effective and die.
3. Results
3.1 clinical symptoms
After being attacked by toxin, the healthy pigs all have symptoms of different degrees, mainly including dyspnea, depression, inappetence, anorexia. After the pigs in the model control group are attacked, purple spots appear on the backs, purple areas appear on the abdomens, and the pigs die after 2 d; after the positive control group of pigs are administrated, the fever symptom is temporarily relieved, but pathogenic microorganisms are not killed fundamentally, the duration of the fever symptom is long, and part of pigs die only from the third day; in the test groups 1-3, the symptoms of the pigs are obviously improved 12h after the administration, the pigs begin to eat, and the mental state begins to improve.
3.2 pathological changes
After death of the sick pig, the lung lobular interstitial edema is enlarged through dissection, the diseased part is solid, dark red and grayish red liquid seeps out of the section, and marble-like diseased parts exist; there are obvious secretions in the bronchi; there is a large amount of fluid in the pericardium; the mucous membrane of the small intestine is congested, and the inside of the mucous membrane is full of yellow mucus; chest lymph nodes are congested and swollen.
3.3 clinical efficacy
The clinical efficacy is shown in table 1.
As can be seen from Table 1, the effective rate of the test 1 group and the test 3 group reaches 90%, the effective rate of the test 2 group reaches 95%, the effective rate of the positive control group reaches 65%, and all pigs in the model control group die. Therefore, the veterinary doxycycline soluble powder medicament has a remarkable treatment effect on swine plague, and can improve the effective rate of diseased swinery by 25-30% compared with the direct use of raw material medicaments.
The doxycycline is reversibly combined with a receptor on a bacterial ribosome 30S subunit to interfere tRNA and mRNA to form a ribosome complex, so that the peptide chain is prevented from being prolonged to inhibit protein synthesis, the growth and the reproduction of bacteria are rapidly inhibited, and the doxycycline plays a role in stabilizing drug effect by adding the trimethoprim lactate, so that the inhibition effect of the doxycycline on gram positive bacteria and gram negative bacteria is more prominent. When in use, the feed additive can be dissolved in water for feeding, can also be directly mixed with feed for feeding, and is convenient to use. The veterinary doxycycline soluble powder has good medicament effect, quick response, simple and feasible preparation method, low cost, convenience for large-scale industrial production and contribution to popularization and application.
Claims (4)
1. The veterinary doxycycline soluble powder medicine is characterized in that every 100g of medicine comprises the following components: 9-11g of doxycycline, 1.5-2.5g of trimethoprim lactate and the balance of anhydrous glucose.
2. The soluble doxycycline powder for veterinary use of claim 1, wherein the composition per 100g of the medicament is: 10g of doxycycline, 2g of trimethoprim lactate and the balance of anhydrous glucose.
3. A process for the preparation of the soluble doxycycline powder for veterinary use as claimed in claim 1 or 2, characterized by comprising the following steps:
(1) respectively pulverizing doxycycline, trimethoprim lactate and anhydrous glucose, and sieving;
(2) weighing doxycycline and trimethoprim lactate according to the prescription amount after sieving in the step (1), adding anhydrous glucose with the same amount as the sum of the weights of the two components, premixing for 15 minutes according to a dispersion method, adding the rest of anhydrous glucose, fully mixing for 40 minutes, uniformly mixing, crushing again and sieving to obtain the doxycycline and trimethoprim lactate.
4. The process for the preparation of a soluble doxycycline powder for veterinary use according to claim 3, wherein: the mesh number of the crushing and sieving screen is 80 meshes.
Priority Applications (1)
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CN201811097110.9A CN110917140A (en) | 2018-09-20 | 2018-09-20 | Veterinary doxycycline soluble powder medicine and preparation method thereof |
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CN201811097110.9A CN110917140A (en) | 2018-09-20 | 2018-09-20 | Veterinary doxycycline soluble powder medicine and preparation method thereof |
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CN201811097110.9A Pending CN110917140A (en) | 2018-09-20 | 2018-09-20 | Veterinary doxycycline soluble powder medicine and preparation method thereof |
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Application publication date: 20200327 |