CN114917193A - Chlortetracycline hydrochloride soluble powder suitable for complex water quality and preparation method thereof - Google Patents
Chlortetracycline hydrochloride soluble powder suitable for complex water quality and preparation method thereof Download PDFInfo
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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
- A61K31/65—Tetracyclines
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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
- A61K9/143—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 inorganic compounds
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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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses chlortetracycline hydrochloride soluble powder suitable for complex water quality and a preparation method thereof, and particularly relates to the technical field of veterinary drugs. The chlortetracycline hydrochloride soluble powder prepared by the invention comprises: according to the mass parts, 20 parts of aureomycin hydrochloride, 3-7 parts of soybean phospholipid, 0.5-2 parts of solubilizer, 0.1-0.5 part of vitamin C, 0.05-0.5 part of dimercaptoethylglycine, 2-7 parts of anhydrous sodium dihydrogen phosphate, 2-7 parts of anhydrous disodium hydrogen phosphate and 56-72.35 parts of anhydrous glucose. The aureomycin hydrochloride soluble powder prepared by the invention has better material compatibility, good high-temperature and high-humidity stability, can adapt to water quality with different hardness, clinical water quality and water with different pH values, and has high stability and high bioavailability after dissolution.
Description
Technical Field
The invention relates to the technical field of veterinary medicines, in particular to chlortetracycline hydrochloride soluble powder suitable for complex water quality and a preparation method thereof.
Background
The chlortetracycline hydrochloride is an active component biosynthesized by the streptomyces aureofaciens and is a tetracyclic antibiotic. The chlortetracycline hydrochloride soluble powder is prepared by hydrochloride of tetracycline broad-spectrum antibacterial chlortetracycline and proper auxiliary materials. The chlortetracycline hydrochloride soluble powder has strong effect on gram-positive bacteria such as staphylococcus, hemolytic streptococcus, bacillus anthracis, clostridium tetani, clostridium clostridia and the like; the antibacterial agent is sensitive to gram-negative bacteria such as escherichia coli, salmonella, brucella, pasteurella and the like, and has stronger antibacterial action than tetracycline and terramycin. The chlortetracycline hydrochloride soluble powder serving as a veterinary chemical plays an important role in the development of animal husbandry, and the market demand is continuously expanded. At present, the chlortetracycline hydrochloride soluble powder is generally taken by drinking water in clinic, is used for treating chronic respiratory diseases of chickens and Escherichia coli diseases, and is also commonly used for preventing and treating mycoplasma. Due to the structural characteristics of tetracycline drug molecules, chlortetracycline hydrochloride molecules can be chelated with polyvalent metal ions such as magnesium, calcium, aluminum and the like in water and gastrointestinal tracts to form insoluble chelates, so that the solubility of the drug in water is reduced, water line blockage is caused, the absorption in the gastrointestinal tracts is incomplete, the bioavailability is low and the like. Chlortetracycline hydrochloride, high concentration dense water is easy to be separated out when hardness in water is great, and dilutes after separating out and also dissolves hardly, can lead to solution content to descend, influences the result of use, and blocks up the doser easily, brings unnecessary trouble for the process of raising. And as the water quality of the clinical culture water is extremely complex, and has the characteristics of high hardness, large pH value change range, excessive microorganism content and metabolite and the like, the complex water quality brings great problems to the application of tetracycline products administrated by drinking water. Therefore, for complex water quality, the development of the chlortetracycline hydrochloride soluble powder which has good stability and can adapt to various complex water quality is needed.
At present, Chinese patent document CN104622811A discloses a formula of veterinary aureomycin hydrochloride soluble powder and a preparation method thereof in 2015, 5 months and 20 days, and improves the stability and bioavailability of the aureomycin hydrochloride soluble powder by adding lauryl sodium sulfate as an absorption enhancer and disodium edetate as an antioxidant and a chelating agent, but the long-term stability of the product is poor; chinese patent document CN107951843A discloses a chlortetracycline hydrochloride soluble powder and a preparation method thereof in 24.4.2018.A crushed raw material is mixed with water and then vibrated to obtain a raw material aqueous solution, and the aqueous solution is dried and granulated to obtain the chlortetracycline hydrochloride soluble powder with better stability and solubility, but carbomer is not dissolved in water, the viscosity of a liquid medicine is increased during concentration, and the thickening effect is influenced by a pH value; chinese patent document CN112641729A discloses a high water-solubility aureomycin hydrochloride soluble powder and a preparation method thereof in 2021, 4.13.A functional cosolvent is adopted to improve the solubility of the aureomycin hydrochloride soluble powder, but the solubility and the stability of the dissolved liquid medicine are easily influenced by complex water quality; chinese patent document CN113332247A discloses a chlortetracycline hydrochloride soluble powder at 9/3/2021, and a preparation method and application thereof, and the use of a functional regulator improves the solubility stability in hard water, artificial gastric juice and intestinal juice, but the solubility stability in complex clinical water is unknown.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides the chlortetracycline hydrochloride soluble powder which is suitable for complex water quality including clinical water quality.
The invention provides chlortetracycline hydrochloride soluble powder suitable for complex water quality, which comprises the following components: according to parts by weight, 20 parts of aureomycin hydrochloride, 3-7 parts of soybean phospholipid, 0.5-2 parts of solubilizer, 0.1-0.5 part of vitamin C, 0.05-0.5 part of dimercaptoethylglycine, 2-7 parts of anhydrous sodium dihydrogen phosphate, 2-7 parts of anhydrous disodium hydrogen phosphate and 56-72.35 parts of anhydrous glucose.
Further, the aureomycin hydrochloride soluble powder comprises, by weight, 20 parts of aureomycin hydrochloride, 4.5 parts of soybean lecithin, 1.2 parts of a solubilizer, 0.3 part of vitamin C, 0.25 part of dimercaptoethylglycine, 3 parts of anhydrous sodium dihydrogen phosphate, 3 parts of anhydrous disodium hydrogen phosphate and 67.75 parts of anhydrous glucose.
Further, the mass ratio of the anhydrous sodium dihydrogen phosphate to the anhydrous disodium hydrogen phosphate is 1: 1.
Further, the solubilizer is poloxamer 188.
Further, the mass ratio of the vitamin C to the dimercaptoethylglycine is (1-10): 1.
The invention also provides a preparation method of the chlortetracycline hydrochloride soluble powder suitable for complex water quality, which comprises the following steps:
s1, weighing the raw materials according to the formula for later use;
s2, dissolving soybean phospholipid in a solvent, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, adding poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer, and mixing;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and mixing to obtain the chlortetracycline hydrochloride soluble powder.
Further, in the step S1, the poloxamer 188, the vitamin C, the dimercaptoethylglycine and the anhydrous glucose are screened by a 100-mesh screen.
Further, the solvent in step S2 is an ethanol aqueous solution with a concentration of 30% by volume.
Further, the mixing time of step S3 is 15 minutes.
Further, the mixing time in step S4 is 15 minutes.
Compared with the prior art, the invention has the beneficial effects that:
1. the components of the chlortetracycline hydrochloride soluble powder prepared by the invention are cooperated to play a role, and through stability test investigation, the compatibility of materials is good, each detection index has no obvious change with the 0 th month in the accelerated investigation period of 6 months, and the chlortetracycline hydrochloride soluble powder has good stability;
2. the aureomycin hydrochloride soluble powder prepared by the invention comprises the components of soybean phospholipid and auxiliary materials such as aureomycin hydrochloride and the like to form a solution, and liposome powder is formed after spray drying, so that the stability and the dissolution rate of aureomycin hydrochloride are improved, the absorption in the stomach is promoted, and the bioavailability is further improved;
3. poloxamer 188 is used as a solubilizer for the aureomycin hydrochloride soluble powder prepared by the invention, so that the solubility of the aureomycin hydrochloride soluble powder in water is improved; vitamin C is used as an auxiliary dimercaptoethylglycine and is used as a medicine molecule protective agent, so that on one hand, the oxidation resistance of the chlortetracycline hydrochloride soluble powder is improved, on the other hand, the chelation effect of the dimercaptoethylglycine and metal ions such as calcium and magnesium in water is also improved, further, the chlortetracycline hydrochloride molecules are prevented from being interfered by the metal ions, and the stability of the chlortetracycline hydrochloride soluble powder after being dissolved in the water is improved;
4. the clinical water quality is complex, and the aureomycin hydrochloride soluble powder, the anhydrous sodium dihydrogen phosphate and the anhydrous disodium hydrogen phosphate prepared by the invention are prepared with an acid-base buffer system according to a ratio of 1:1, so that the pH of the buffer system is close to neutral, and the tolerance of the aureomycin hydrochloride soluble powder to clinical water with different pH values is enhanced.
Detailed Description
To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, 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 invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
Materials, reagents, equipment sources:
materials and equipment used in the embodiment are all commercially available sources unless otherwise specified; unless otherwise specified, all the experimental methods are routine in the art.
Example 1 chlortetracycline hydrochloride soluble powder suitable for complex water quality and preparation thereof
The formula is as follows: 20kg of chlortetracycline hydrochloride, 4.5kg of soybean phospholipid, 1881.2 kg of poloxamer, 0.3kg of vitamin C, 0.25kg of dimercaptoethylglycine, 3kg of anhydrous sodium dihydrogen phosphate, 3kg of anhydrous disodium hydrogen phosphate and 67.75kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving soybean phospholipid in 30 volume percent ethanol water solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, and putting the dried mixed solution, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer to mix for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
Example 2 chlortetracycline hydrochloride soluble powder suitable for complex water quality and preparation thereof
The formula is as follows: 20kg of chlortetracycline hydrochloride, 3kg of soybean lecithin, 1880.5 kg of poloxamer, 0.1kg of vitamin C, 0.05kg of dimercaptoethylglycine, 2kg of anhydrous sodium dihydrogen phosphate, 2kg of anhydrous disodium hydrogen phosphate and 72.35kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving soybean phospholipid in 30 volume percent ethanol water solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, and putting the dried mixed solution, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer to mix for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
Example 3 chlortetracycline hydrochloride soluble powder suitable for complex water quality and preparation thereof
The formula is as follows: 20kg of chlortetracycline hydrochloride, 7kg of soybean phospholipid, 1882 kg of poloxamer, 0.5kg of vitamin C, 0.5kg of dimercaptoethylglycine, 7kg of anhydrous sodium dihydrogen phosphate, 7kg of anhydrous disodium hydrogen phosphate and 56kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving soybean phospholipid in 30 volume percent ethanol water solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, and putting the spray-dried mixed solution, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer for mixing for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
Comparative example 1
The formula is as follows: 20kg of chlortetracycline hydrochloride, 1881.2 kg of poloxamer, 0.3kg of vitamin C, 0.25kg of dimercaptoethylglycine, 3kg of anhydrous sodium dihydrogen phosphate, 3kg of anhydrous disodium hydrogen phosphate and 72.25kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount respectively; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, putting aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate, anhydrous disodium hydrogen phosphate, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer, and mixing for 15 minutes;
and S3, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
This comparative example differs from example 1 in that no soybean lecithin was added and no spray drying was performed.
Comparative example 2
The formula is as follows: 20kg of chlortetracycline hydrochloride, 4.5kg of lecithin, 1881.2 kg of poloxamer, 0.3kg of vitamin C, 0.25kg of dimercaptoethylglycine, 3kg of anhydrous sodium dihydrogen phosphate, 3kg of anhydrous disodium hydrogen phosphate and 67.75kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving lecithin in 30% ethanol water solution by volume percentage, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, and putting the spray-dried mixed solution, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer for mixing for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
This comparative example is different from example 1 in that soybean phospholipid was changed to lecithin.
Comparative example 3
The formula is as follows: 20kg of chlortetracycline hydrochloride, 4.5kg of soybean phospholipid, 1881.2 kg of poloxamer, 0.3kg of vitamin C, 0.25kg of dimercaptoethylglycine, 4kg of anhydrous sodium dihydrogen phosphate, 2kg of anhydrous disodium hydrogen phosphate and 67.75kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving soybean phospholipid in 30% ethanol solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain mixed solution;
s3, spray-drying the mixed solution, and putting the spray-dried mixed solution, poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer for mixing for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
This comparative example differs from example 1 in that the ratio of anhydrous sodium dihydrogen phosphate to anhydrous disodium hydrogen phosphate is 4: 2.
Comparative example 4
The formula is as follows: 20kg of chlortetracycline hydrochloride, 4.5kg of soybean phospholipid, 1881.2 kg of poloxamer, 0.3kg of vitamin C, 0.25kg of sodium citrate, 3kg of anhydrous sodium dihydrogen phosphate, 3kg of anhydrous disodium hydrogen phosphate and 67.75kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount respectively; wherein poloxamer 188, vitamin C, sodium citrate and anhydrous glucose are sieved by a 100-mesh sieve for standby;
s2, dissolving soybean phospholipid in 30 volume percent ethanol water solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, and putting the spray-dried mixed solution, poloxamer 188, vitamin C and sodium citrate into a three-dimensional mixer to mix for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
This comparative example differs from example 1 in that dimercaptoethylglycine is changed to sodium citrate.
Comparative example 5
The formula is as follows: 20kg of chlortetracycline hydrochloride, 4.5kg of soybean phospholipid, 1881.2 kg of poloxamer, 0.25kg of dimercaptoethylglycine, 3kg of anhydrous sodium dihydrogen phosphate, 3kg of anhydrous disodium hydrogen phosphate and 68.05kg of anhydrous glucose
The preparation process comprises the following steps:
s1, weighing the raw materials according to the formula amount respectively; wherein poloxamer 188, dimercaptoethylglycine and anhydrous glucose are screened by a 100-mesh screen for standby;
s2, dissolving soybean phospholipid in 30 volume percent ethanol water solution, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, adding poloxamer 188 and dimercaptoethylglycine into a three-dimensional mixer, and mixing for 15 minutes;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
This comparative example differs from example 1 in that no vitamin C is added.
Test example I, stability test of chlortetracycline hydrochloride soluble powder
(1) Test samples: chlortetracycline hydrochloride soluble powder prepared in examples 1-3 and comparative examples 1-2
(2) The test method comprises the following steps:
respectively placing a chlortetracycline hydrochloride soluble powder sample under the conditions of high temperature (60 ℃) and high humidity (relative humidity is 95% +/-5%), and sampling on the 5 th day and the 10 th day to detect according to the quality standard;
placing a chlortetracycline hydrochloride soluble powder sample for 6 months under the conditions of 40 +/-2 ℃ and 75% +/-5% of humidity, carrying out accelerated stability test, and respectively sampling in 1 month, 2 months, 3 months and 6 months for detection according to quality standards;
(3) test results
TABLE 1 stability test results of chlortetracycline hydrochloride soluble powder
As can be seen from the data in table 1, in a high-temperature and high-humidity environment for 10 days and within a time period of 6 months of an accelerated test, each detection index of the aureomycin hydrochloride soluble powder prepared in the embodiments 1 to 3 of the present invention is within a qualified range, and the change is not obvious compared with the 0 th month, which indicates that the formula material compatibility of the aureomycin hydrochloride soluble powder of the present invention is good and stable, wherein the change index of the aureomycin hydrochloride soluble powder prepared in the embodiment 1 is the minimum, and is the best embodiment of the present invention; in the comparative example 1, as no soybean phospholipid is added, liposome powder cannot be formed after spray drying, the prepared chlortetracycline hydrochloride soluble powder has poor stability, and can quickly change color and agglomerate in high-temperature, high-humidity and accelerated environments; comparative example 2 since lecithin was used instead of soybean lecithin, stability was also lowered, and discoloration and caking were also easily caused even in a high-temperature, high-humidity, accelerated environment for a long time.
Test example II content stability test of chlortetracycline hydrochloride soluble powder dissolved in water of different hardness
(1) Test samples: chlortetracycline hydrochloride soluble powder prepared in examples 1-3 and comparative examples 4-5
(2) The test method comprises the following steps:
preparing water with different hardness:
demineralized water (hardness standard <150 mkg/L);
medium hardness water (hardness standard 150-300 mkg/L): dissolving 0.152kg of anhydrous magnesium chloride and 0.0695kg of crystallized magnesium chloride in water, and fixing the volume to 1000 ml;
high hardness water (hardness standard 300-450 mkg/L): dissolving 0.304kg of anhydrous magnesium chloride and 0.139kg of crystalline magnesium chloride in water, and then fixing the volume to 1000 mL;
the clinical water 1 is tap water; the clinical water 2 is river water;
the test process comprises the following steps: respectively taking 0.2kg of the aureomycin hydrochloride soluble powder prepared in the examples 1-3 and the comparative examples 4-5, precisely weighing, respectively dissolving with water with different hardness and clinical water 1-2, fixing the volume to 100mL with water with corresponding hardness, precisely taking 20 mu L of water solution after 0, 4, 8, 12 and 24h after dissolution, filtering with a 0.45 mu m filter membrane, injecting into a liquid chromatograph, and recording a chromatogram; and calculating the content of chlortetracycline hydrochloride in the solution according to an external standard method.
(3) And (3) test results: the results are shown in the following table:
TABLE 2 content of chlortetracycline hydrochloride soluble powder in different hardness water and clinical water
As can be seen from the data in Table 2, in the observation period of standing for 24 hours after dissolution, the marked content of the solution is not obviously changed after the aureomycin hydrochloride soluble powder samples prepared in the embodiments 1-3 of the invention are dissolved in the water quality with different hardness and the clinical water quality, and the solution is still stable after 24 hours; the variation of the embodiment 1 is the most obvious and is the best embodiment of the invention; in the high-hardness water quality and the clinical water quality 1-2, the chlortetracycline hydrochloride soluble powder sample prepared in the comparative example 4 has no good chelation effect with metal ions such as calcium, magnesium and the like in water because the dimercaptoethylglycine is changed into sodium citrate, and is separated out and precipitated along with the time extension after being dissolved, so that the labeled content is obviously reduced, and the stability is poor; the chlortetracycline hydrochloride soluble powder prepared in the comparative example 5 has no vitamin C added, does not have vitamin C auxiliary dimercaptoethylglycine, has reduced oxidation resistance and chelation effect of dimercaptoethylglycine and metal ions such as calcium and magnesium in water, cannot avoid the interference of chlortetracycline hydrochloride molecules by the metal ions, and has obviously reduced stability after a sample is dissolved in water, particularly clinical water quality 1-2, so that the identification content is obviously reduced along with the prolonging of time.
Test example III test of content stability of chlortetracycline hydrochloride soluble powder dissolved in aqueous solutions of different pH values
(1) Test samples: aureomycin hydrochloride soluble powders prepared in examples 1-3 and comparative example 3
(2) The test method comprises the following steps:
taking a proper amount of purified water, and adjusting the pH value to 5.0 +/-0.2 by using a hydrochloric acid solution;
taking a proper amount of purified water, and adjusting the pH value to 9.0 +/-0.2 by using a sodium hydroxide solution;
0.2kg of the aureomycin hydrochloride soluble powder prepared in the examples 1-3 and the comparative example 3 are taken, precisely weighed, respectively dissolved by water with different pH values, the volume is determined to be 100mL by water with corresponding pH values, 20 mu L of aqueous solution is precisely taken in 0, 4, 8, 12 and 24h after dissolution, the aqueous solution passes through a 0.45 mu m filter membrane and is injected into a liquid chromatograph, and a chromatogram is recorded; calculating the content of chlortetracycline hydrochloride in the solution according to an external standard method;
(3) and (3) test results: the results are shown in the following table:
TABLE 3 table of content stability of chlortetracycline hydrochloride soluble powder in water of different pH
As can be seen from the data in Table 3, within an observation period of 24 hours after the aureomycin hydrochloride soluble powder prepared in the embodiments 1-3 of the invention is dissolved in aqueous solutions with different pH values, the marked content of the aqueous solution is not obviously changed, the aqueous solution is relatively stable, and the tolerance of the aqueous solution to clinical water with different pH values is stronger, wherein the content of the embodiment 1 is the most obviously changed and is the best embodiment of the invention; the ratio of the anhydrous sodium dihydrogen phosphate to the anhydrous disodium hydrogen phosphate of the aureomycin hydrochloride soluble powder prepared in the comparative example 3 is 4:2, the pH of the buffer system is not nearly neutral, the tolerance of the aureomycin hydrochloride soluble powder to the pH value is influenced, so the labeled content of the aureomycin hydrochloride soluble powder in the aqueous solution with the pH value of 9.0 is obviously reduced to 85.4%.
The technical principle of the present invention is described above in connection with specific embodiments. The description is made for the purpose of illustrating the principles of the invention and should not be taken in any way as limiting the scope of the invention. Based on the explanations herein, those skilled in the art will be able to conceive of other embodiments of the present invention without inventive effort, which would fall within the scope of the present invention.
Claims (10)
1. The chlortetracycline hydrochloride soluble powder suitable for complex water quality is characterized by comprising: according to parts by weight, 20 parts of aureomycin hydrochloride, 3-7 parts of soybean phospholipid, 0.5-2 parts of solubilizer, 0.1-0.5 part of vitamin C, 0.05-0.5 part of dimercaptoethylglycine, 2-7 parts of anhydrous sodium dihydrogen phosphate, 2-7 parts of anhydrous disodium hydrogen phosphate and 56-72.35 parts of anhydrous glucose.
2. The chlortetracycline hydrochloride soluble powder suitable for complex water quality of claim 1, wherein the mass ratio of anhydrous sodium dihydrogen phosphate to anhydrous disodium hydrogen phosphate is 1: 1.
3. The chlortetracycline hydrochloride soluble powder suitable for complex water quality of claim 1, wherein the solubilizer is poloxamer 188.
4. The chlortetracycline hydrochloride soluble powder suitable for complex water quality as claimed in claim 1, wherein the mass ratio of vitamin C to dimercaptoethylglycine is (1-10): 1.
5. The chlortetracycline hydrochloride soluble powder suitable for complex water quality according to claim 1, comprising: according to the weight portion, 20 portions of chlortetracycline hydrochloride, 4.5 portions of soybean phospholipid, 1.2 portions of solubilizer, 0.3 portion of vitamin C, 0.25 portion of dimercaptoethylglycine, 3 portions of anhydrous sodium dihydrogen phosphate, 3 portions of anhydrous disodium hydrogen phosphate and 67.75 portions of anhydrous glucose.
6. The preparation method of the chlortetracycline hydrochloride soluble powder adapting to the complex water quality as in any one of claims 1-5, characterized by comprising the following steps:
s1, weighing the raw materials according to the prescription amount for later use;
s2, dissolving soybean phospholipid in a solvent, adding chlortetracycline hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spray-drying the mixed solution, adding poloxamer 188, vitamin C and dimercaptoethylglycine into a three-dimensional mixer, and mixing;
and S4, adding the anhydrous glucose into a three-dimensional mixer, and mixing to obtain the chlortetracycline hydrochloride soluble powder.
7. The method for preparing chlortetracycline hydrochloride soluble powder suitable for complex water quality as claimed in claim 5, wherein in step S1, poloxamer 188, vitamin C, dimercaptoethylglycine and anhydrous glucose are sieved with 100 mesh sieve.
8. The method for preparing chlortetracycline hydrochloride soluble powder adapting to complex water quality as in claim 5, wherein the solvent in step S2 is an ethanol aqueous solution with a volume percentage concentration of 30%.
9. The method for preparing chlortetracycline hydrochloride soluble powder suitable for complex water quality according to claim 5, wherein the mixing time of step S3 is 15 minutes.
10. The method for preparing the chlortetracycline hydrochloride soluble powder adapting to the complex water quality as in claim 5, wherein the mixing time in step S4 is 15 minutes.
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| CN101600418A (en) * | 2006-12-19 | 2009-12-09 | 先灵-普劳有限公司 | Be used for adding the effervescent formulation of the florfenicol of drinking-water system |
| CN104721143A (en) * | 2015-02-13 | 2015-06-24 | 正大联合动物制药科技（江苏）有限公司 | Stable and efficient chlortetracycline hydrochloride soluble powder for livestock and preparation technology thereof |
| CN105380901A (en) * | 2015-11-18 | 2016-03-09 | 侯宇华 | Tafluprost eye drop and preparation method thereof |
| CN110507616A (en) * | 2019-08-26 | 2019-11-29 | 佛山市正典生物技术有限公司 | A kind of aureomycin hydrochloride soluble powder and preparation method thereof |
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| CN101600418A (en) * | 2006-12-19 | 2009-12-09 | 先灵-普劳有限公司 | Be used for adding the effervescent formulation of the florfenicol of drinking-water system |
| CN104721143A (en) * | 2015-02-13 | 2015-06-24 | 正大联合动物制药科技（江苏）有限公司 | Stable and efficient chlortetracycline hydrochloride soluble powder for livestock and preparation technology thereof |
| CN105380901A (en) * | 2015-11-18 | 2016-03-09 | 侯宇华 | Tafluprost eye drop and preparation method thereof |
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