CN112220755A - Doxycycline hydrochloride soluble powder and preparation method thereof - Google Patents
Doxycycline hydrochloride soluble powder and preparation method thereof Download PDFInfo
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- CN112220755A CN112220755A CN202011310647.6A CN202011310647A CN112220755A CN 112220755 A CN112220755 A CN 112220755A CN 202011310647 A CN202011310647 A CN 202011310647A CN 112220755 A CN112220755 A CN 112220755A
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- soluble powder
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- doxycycline hydrochloride
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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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
Abstract
The invention discloses doxycycline hydrochloride soluble powder and a preparation method thereof, wherein each 100 parts of doxycycline hydrochloride soluble powder comprises the following raw materials in parts by weight: 10-50 parts of doxycycline hydrochloride, 1-3 parts of complexing agent, 1-5 parts of antioxidant, 1-5 parts of surfactant and the balance of filler; during preparation, the raw materials are weighed according to the weight ratio, and the weighed raw materials are crushed and sieved by a sieve of 80-100 meshes; the crushed raw materials are put into a mixer for mixing uniformly, the rotating speed of the mixer is 5000-; mixing uniformly to obtain the product; the invention adopts a simple mixing process to obtain doxycycline hydrochloride soluble powder. Improves the solubility and thus the bioavailability. The prepared product has high solubility, good fluidity, low moisture and good stability, and meets the quality standard of veterinary drugs.
Description
Technical Field
The invention relates to the technical field of veterinary drug preparations, in particular to doxycycline hydrochloride soluble powder and a preparation method thereof.
Background
Doxycycline hydrochloride, also known as doxycycline, is a pale yellow or yellow crystalline powder, smelly, bitter in taste, readily soluble in water or methanol, slightly soluble in ethanol or acetone, and insoluble in chloroform.
Doxycycline hydrochloride is a second-generation semisynthetic tetracycline derivative, is an excellent veterinary spectral antibiotic, has a strong inhibiting effect on gram-negative bacteria, gram-positive bacteria, spirochetes, rickettsiae, chlamydia, mycoplasma and other pathogenic bacteria, is widely used for treating bacterial diseases of livestock and poultry caused by sensitive bacteria, and is mainly used for treating respiratory tract, urinary tract and biliary tract infections caused by the sensitive bacteria.
At present, doxycycline hydrochloride premixes, solutions, soluble powders, injections and the like are mainly available on the market. Based on the consideration of the aspect of convenient administration, the research of doxycycline hydrochloride soluble powder is paid attention. Generally, doxycycline hyclate soluble powder is obtained by mixing doxycycline and glucose, but the problem that the effective content is reduced and even the effective content is lost due to poor stability when the doxycycline hyclate soluble powder is mixed with water for use is solved.
On one hand, doxycycline hydrochloride may produce isomers under the action of light, acid and alkali in the processes of storage, transportation and medication; on the other hand, doxycycline hydrochloride is easy to perform a complex reaction with metal ions in water, and the generated complex is difficult to absorb; on the other hand, the doxycycline hydrochloride contains easily oxidized and hydrolyzed groups such as phenolic hydroxyl, enol group and amide group in the structure, so that the doxycycline hydrochloride is easily oxidized and decomposed by heating or in a solution. The effective content of doxycycline hydrochloride is reduced and the treatment effect is poor. Therefore, the study on the stability of doxycycline hydrochloride soluble powder in the prior art cannot be said to be sufficient, and further improvement is needed. Therefore, the research and development of the doxycycline hydrochloride soluble powder and the preparation method thereof have very important significance.
Disclosure of Invention
Aiming at the problems of reduced effective content, poor treatment effect and the like of the existing doxycycline hydrochloride soluble powder, the invention provides doxycycline hydrochloride soluble powder and a preparation method thereof.
In order to realize the purpose, the invention is realized by the following technical scheme:
the invention relates to doxycycline hydrochloride soluble powder, which comprises the following raw materials in 100 parts by weight: 10-50 parts of doxycycline hydrochloride, 1-3 parts of complexing agent, 1-5 parts of antioxidant, 1-5 parts of surfactant and the balance of filler.
Preferably, the complexing agent in the invention is disodium edetate tetraacetate.
Preferably, the antioxidant in the invention is one or a mixture of citric acid and sodium citrate.
Preferably, the surfactant in the invention is one or a mixture of span 20 and Arabic gum.
Preferably, the filler in the invention is one or two mixtures of sucrose, anhydrous glucose, lactose and soluble starch.
The invention also provides a preparation method of the doxycycline hydrochloride soluble powder, which comprises the following steps:
(1) weighing the raw materials according to the weight ratio, crushing the weighed raw materials, and sieving the crushed raw materials by a sieve of 80-100 meshes;
(2) the crushed raw materials are put into a mixer for mixing uniformly, the rotating speed of the mixer is 5000-;
(3) and uniformly mixing to obtain doxycycline hydrochloride soluble powder.
The invention adopts a simple mixing process to obtain doxycycline hydrochloride soluble powder. Improves the solubility and thus the bioavailability. The prepared product has high solubility, good fluidity, low moisture and good stability, and meets the quality standard of veterinary drugs.
The invention is widely used for treating bacterial diseases of livestock and poultry caused by sensitive bacteria, and is mainly used for treating respiratory tract, urinary tract and biliary tract infections caused by the sensitive bacteria. The invention has mature process, is easy to realize large-scale production and has high economic effect.
Detailed Description
The present invention is further illustrated by the following examples, but the present invention is not limited to the following examples.
Example 1
Every 100g of the doxycycline hydrochloride soluble powder comprises the following raw materials: 50g of doxycycline hydrochloride, 2g of disodium edetate, 5g of citric acid, 4g of span 20 and 39g of anhydrous glucose. During preparation, the raw materials are weighed according to the weight, and the weighed raw materials are crushed and sieved by a sieve of 80-100 meshes; the crushed raw materials are put into a mixer for mixing uniformly, the rotating speed of the mixer is 5000-; and uniformly mixing to obtain doxycycline hydrochloride soluble powder.
Example 2
Every 100g of the doxycycline hydrochloride soluble powder comprises the following raw materials: 10g of doxycycline hydrochloride, 2g of disodium edetate, 5g of citric acid, 4g of Arabic gum and 79g of sucrose. During preparation, the raw materials are weighed according to the weight, and the weighed raw materials are crushed and sieved by a sieve of 80-100 meshes; the crushed raw materials are put into a mixer for mixing uniformly, the rotating speed of the mixer is 5000-; and uniformly mixing to obtain doxycycline hydrochloride soluble powder.
Example 3
Comparative example 1 is doxycycline hydrochloride soluble powder purchased from company a, ltd, and comparative example 2 is doxycycline hydrochloride soluble powder purchased from company B, biotechnology ltd, on the market.
Taking the samples prepared in example 1 and example 2 and the samples of comparative example 1 and comparative example 2, the stability acceleration test was performed. Each example and each comparative example take 6 parts of doxycycline hydrochloride soluble powder, each 10g of doxycycline hydrochloride soluble powder, simulate to be packaged on the market, completely encapsulate with an aluminum foil bag, seal a layer of white plastic bag outside, then put into a full paper box, place into a constant temperature and humidity box, and have the temperature of 40 +/-2 ℃; the relative humidity is 75 +/-5%, and the content is sampled and detected every month.
According to the detection method of doxycycline hydrochloride soluble powder in 'Chinese veterinary pharmacopoeia' 2015 edition, a proper amount of samples (equivalent to doxycycline 0.1mg/ml) in the examples and the comparative examples are taken, and 0.01mol/L hydrochloric acid solution is added to dissolve the samples and dilute the samples into solution containing 0.1mg of doxycycline per 1 ml. Octadecylsilane chemically bonded silica is used as a filling agent (the pH value application range is larger than 9), acetate buffer solution (0.25mol/L ammonium acetate-0.1 mol/L disodium ethylene diamine tetraacetate-triethylamine (100: 10:1) is used, glacial acetic acid or ammonia water is used for adjusting the pH value to 8.8) -acetonitrile (85:15) is used as a mobile phase, the column temperature is 35 ℃, the detection wavelength is 280nm, the flow rate is 1.0ml/min, and the sample injection volume is 20 mu L. Respectively measuring at 0, 1, 2, 3, 4, 5 and 6 months by using a high performance liquid chromatograph, and calculating the content by peak area according to an external standard method.
Table 1: accelerated test comparative results (solubility)
| 0 month | 1 month | 2 month | 3 month | 4 month | Month 5 | 6 month | |
| Example 1 | Clarification | Clarification | Clarification | Clarification | Clarification | Clarification | Clarification |
| Example 2 | Clarification | Clarification | Clarification | Clarification | Clarification | Clarification | Clarification |
| Comparative example 1 | Slight turbidity | Clarification | Clarification | Clarification | Precipitation out of the precipitate | Precipitation out of the precipitate | Precipitation out of the precipitate |
| Comparative example 2 | Slight turbidity | Clarification | Clarification | Clarification | Precipitation out of the precipitate | Precipitation out of the precipitate | Precipitation out of the precipitate |
Table 2: indicating amount (%)
| 0 month | 1 month | 2 month | 3 month | 4 month | Month 5 | 6 month | |
| Example 1 | 99.76 | 99.77 | 99.76 | 99.78 | 99.77 | 99.76 | 99.74 |
| Example 2 | 99.93 | 99.94 | 99.93 | 99.92 | 99.92 | 99.90 | 99.89 |
| Comparative example 1 | 99.05 | 99.67 | 99.66 | 99.68 | 95.74 | 92.62 | 87.26 |
| Comparative example 2 | 98.64 | 99.42 | 99.43 | 99.42 | 96.02 | 92.77 | 87.46 |
From the results in tables 1 and 2 above, it can be seen that the doxycycline hydrochloride soluble powder prepared in examples 1-2 by the method of the present invention can be rapidly dissolved in water, has a good dissolution effect, has a stability superior to that of the comparative example, and has a marked amount of 99% or more after accelerated for 6 months.
Example 4
The doxycycline hydrochloride soluble powder is clinically applied and tested to a certain farm in Wushu city, Hubei province. The test animals are 30-day-old chickens, and the chicken groups mainly have the symptoms of snore, chum with mouth, nasal discharge, unwilling to walk and the like. The chicken flocks were divided into 5 groups of 150 chickens, the first group being the doxycycline hyclate soluble powder treatment group of example 1; the second group was the doxycycline hydrochloride soluble powder treatment group of example 2; the third group is the doxycycline hydrochloride soluble powder treatment group of comparative example 1; the fourth group was the doxycycline hydrochloride soluble powder treatment group of comparative example 2; the fifth group was a blank control group without any drug added.
The above five groups of chickens were fed in the same manner, and the first to fourth groups were treated by drinking water, and the fifth group of chickens were provided with drinking water without any drug. Housing in five independent areas.
Table 3 therapeutic effect (%)
| Group of | High efficiency | Cure rate | Mortality rate |
| First group | 92 | 90 | 9 |
| Second group | 94 | 93 | 9 |
| Third group | 85 | 82 | 26 |
| Fourth group | 83 | 79 | 28 |
| Fifth group | 14 | 6 | 94 |
As can be seen from the results in table 3 above, the doxycycline hydrochloride soluble powder prepared in examples 1 and 2 of the present invention has a very good therapeutic effect on respiratory tract infection of chickens. Therefore, the invention can improve the bioavailability of the doxycycline hydrochloride soluble powder.
The foregoing is illustrative of the preferred embodiments of the present invention, and is not to be construed as limiting thereof, as many variations and modifications are possible in light of the above teaching to those skilled in the art. Equivalent embodiments of this equivalent variation. However, simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention are within the scope of the claims of the present invention, unless departing from the technical idea of the present invention.
Claims (6)
1. The doxycycline hydrochloride soluble powder is characterized in that each 100 parts of doxycycline hydrochloride soluble powder comprises the following raw materials in parts by weight: 10-50 parts of doxycycline hydrochloride, 1-3 parts of complexing agent, 1-5 parts of antioxidant, 1-5 parts of surfactant and the balance of filler.
2. The doxycycline hyclate soluble powder of claim 1, wherein: the complexing agent is disodium edetate tetraacetate.
3. The doxycycline hyclate soluble powder of claim 1, wherein: the antioxidant is one or a mixture of citric acid and sodium citrate.
4. The doxycycline hyclate soluble powder of claim 1, wherein: the surfactant is one or a mixture of span 20 and Arabic gum.
5. The doxycycline hyclate soluble powder of claim 1, wherein: the filler is one or two mixtures of sucrose, anhydrous glucose, lactose and soluble starch.
6. A process for the preparation of doxycycline hyclate soluble powder of any one of claims 1 to 5 comprising the steps of:
(1) weighing the raw materials according to the weight ratio, crushing the weighed raw materials, and sieving the crushed raw materials by a sieve of 80-100 meshes;
(2) the crushed raw materials are put into a mixer for mixing uniformly, the rotating speed of the mixer is 5000-;
(3) and uniformly mixing to obtain doxycycline hydrochloride soluble powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011310647.6A CN112220755A (en) | 2020-11-20 | 2020-11-20 | Doxycycline hydrochloride soluble powder and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011310647.6A CN112220755A (en) | 2020-11-20 | 2020-11-20 | Doxycycline hydrochloride soluble powder and preparation method thereof |
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| Publication Number | Publication Date |
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| CN112220755A true CN112220755A (en) | 2021-01-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011310647.6A Withdrawn CN112220755A (en) | 2020-11-20 | 2020-11-20 | Doxycycline hydrochloride soluble powder and preparation method thereof |
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| Country | Link |
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| CN (1) | CN112220755A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114028410A (en) * | 2021-10-25 | 2022-02-11 | 华南农业大学 | Doxycycline hydrochloride solution and preparation method thereof |
| CN114159547A (en) * | 2021-11-04 | 2022-03-11 | 河南惠康动物药业有限公司 | Doxycycline hydrochloride powder for aquatic products, use method and preparation method thereof |
-
2020
- 2020-11-20 CN CN202011310647.6A patent/CN112220755A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114028410A (en) * | 2021-10-25 | 2022-02-11 | 华南农业大学 | Doxycycline hydrochloride solution and preparation method thereof |
| CN114028410B (en) * | 2021-10-25 | 2023-10-20 | 华南农业大学 | Doxycycline hydrochloride solution and preparation method thereof |
| CN114159547A (en) * | 2021-11-04 | 2022-03-11 | 河南惠康动物药业有限公司 | Doxycycline hydrochloride powder for aquatic products, use method and preparation method thereof |
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Application publication date: 20210115 |