CN114917193B - Aureomycin hydrochloride soluble powder suitable for complex water quality and preparation method thereof - Google Patents
Aureomycin hydrochloride soluble powder suitable for complex water quality and preparation method thereof Download PDFInfo
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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 medicines. The chlortetracycline hydrochloride soluble powder prepared by the invention comprises the following components: the composition comprises, by mass, 20 parts of aureomycin hydrochloride, 3-7 parts of soybean phospholipids, 0.5-2 parts of a solubilizer, 0.1-0.5 part of vitamin C, 0.05-0.5 part of dimercaptoethyl glycine, 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 soluble aureomycin hydrochloride powder prepared by the invention has good material compatibility and high-temperature and high-humidity stability, can adapt to water quality with different hardness, clinical water quality and water with different pH value, 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 aureomycin hydrochloride is an active ingredient for biosynthesis of streptomyces aureofaciens and is a tetracyclic antibiotic. The soluble aureomycin hydrochloride powder is prepared from tetracycline broad-spectrum antibiotic aureomycin hydrochloride and proper auxiliary materials. The chlortetracycline hydrochloride soluble powder has strong effects on gram-positive bacteria such as staphylococcus, hemolytic streptococcus, bacillus anthracis, clostridium tetani, clostridium and the like; is sensitive to gram-negative bacteria such as escherichia coli, salmonella, brucella, pasteurella and the like, and has stronger antibacterial effect than tetracycline and terramycin. The chlortetracycline hydrochloride soluble powder is used as a veterinary chemical, plays an important role in the development of animal husbandry, and the market demand is also continuously expanding. At present, the chlortetracycline hydrochloride soluble powder is clinically administrated by drinking water, is used for treating chronic respiratory diseases and escherichia coli diseases of chickens, and is also commonly used for preventing and treating mycoplasma. Because of the self structural characteristics of tetracycline medicine molecules, the chlortetracycline hydrochloride molecules can be chelated with water and multivalent metal ions such as magnesium, calcium, aluminum and the like in the gastrointestinal tract to form insoluble chelates, so that the solubility of the medicine in water is reduced, and the problems of waterline blockage, incomplete absorption in the gastrointestinal tract, low bioavailability and the like are caused. The chlortetracycline hydrochloride is easy to separate out in high-concentration concentrated water when the hardness in water is high, and the chlortetracycline hydrochloride is difficult to dissolve after being separated out, so that the content of solution is reduced, the use effect is affected, a doser is easy to be blocked, and unnecessary troubles are brought to the cultivation process. And because the water quality of the clinical culture water is extremely complex, the water quality has the characteristics of high hardness, large pH value change range, excessive microorganism content and metabolite and the like, and the complex water quality brings great difficulty to the application of tetracycline products which are administrated by drinking water. Therefore, aiming at complex water quality, it is necessary to develop the chlortetracycline hydrochloride soluble powder which has good stability and can adapt to various complex water quality.
At present, chinese patent document CN104622811A discloses a veterinary chlortetracycline hydrochloride soluble powder formula and a preparation method thereof in 5 months and 20 days of 2015, and the stability and bioavailability of the chlortetracycline hydrochloride soluble powder are improved by adding sodium dodecyl sulfate as an absorption accelerator and disodium edetate as an antioxidant and a chelating agent, but the long-term stability of the product is poor; the Chinese patent document CN107951843A discloses an aureomycin hydrochloride soluble powder and a preparation method thereof in 24 days of 2018, wherein a raw material aqueous solution is obtained by mixing and vibrating a crushed raw material with water, and the aqueous solution is dried and granulated to obtain the aureomycin hydrochloride soluble powder with good stability and solubility, but carbomer is insoluble in water, the viscosity of a liquid medicine is increased during concentration, the thickening effect is influenced by pH value, and in addition, the process is complex, the cost is high, and the method is not suitable for industrialized mass production; chinese patent document CN112641729A discloses a high water-soluble salt aureomycin hydrochloride soluble powder and a preparation method thereof in 2021, wherein the solubility of the aureomycin hydrochloride soluble powder is improved by adopting a functional cosolvent, but the solubility and the stability of the liquid medicine after dissolution are easily influenced by complex water quality; chinese patent document CN113332247A discloses an aureomycin hydrochloride soluble powder in 2021, 9 and 3, as well as a preparation method and application thereof, and through the use of a functional regulator, the dissolution stability in hard water, artificial gastric juice and intestinal juice is improved, but the dissolution stability in complex clinical water quality 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, has good material compatibility, good stability in high-temperature and high-humidity environments, is storage-resistant, can be suitable for water quality with different hardness and water with different pH values, and has high stability after dissolution.
The invention provides chlortetracycline hydrochloride soluble powder suitable for complex water quality, which comprises the following components: the chlortetracycline hydrochloride comprises, by weight, 20 parts of chlortetracycline hydrochloride, 3-7 parts of soybean phospholipids, 0.5-2 parts of solubilizer, 0.1-0.5 part of vitamin C, 0.05-0.5 part of dimercaptoethyl glycine, 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 chlortetracycline hydrochloride soluble powder comprises, by weight, 20 parts of chlortetracycline hydrochloride, 4.5 parts of soybean lecithin, 1.2 parts of a solubilizer, 0.3 part of vitamin C, 0.25 part of dimercaptoethyl glycine, 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 solubilizing agent 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 adapting to complex water quality, which comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount for standby;
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, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C, dimercaptoethyl glycine and the mixture into a three-dimensional mixer for mixing;
s4, throwing anhydrous glucose into a three-dimensional mixer, and mixing to obtain the chlortetracycline hydrochloride soluble powder.
Further, the raw materials of poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose in the step S1 need to be sieved by a 100-mesh sieve.
Further, the solvent in the step S2 is an aqueous ethanol solution with a volume percentage concentration of 30%.
Further, the mixing time in the step S3 is 15 minutes.
Further, the mixing time in the 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 the stability test shows that the material compatibility is good, and all detection indexes have no obvious change with the 0 th month in the accelerated investigation period of 6 months, so that the chlortetracycline hydrochloride soluble powder has good stability;
2. the component of the chlortetracycline hydrochloride soluble powder prepared by the invention comprises soybean lecithin, chlortetracycline hydrochloride and other auxiliary materials to form a solution, and liposome powder is formed after spray drying, so that the stability and dissolution rate of chlortetracycline hydrochloride are improved, the absorption in the stomach is promoted, and the bioavailability is further improved;
3. the soluble powder of the chlortetracycline hydrochloride prepared by the invention uses poloxamer 188 as a solubilizer, so that the solubility of the soluble powder of the chlortetracycline hydrochloride in water is improved; vitamin C is used for assisting dimercaptoethyl glycine as a medicine molecule protective agent, so that on one hand, the oxidation resistance of the chlortetracycline hydrochloride soluble powder is improved, and on the other hand, the chelating effect of the dimercaptoethyl glycine and metal ions such as calcium, magnesium and the like in water is also improved, further, the interference of metal ions on chlortetracycline hydrochloride molecules is avoided, and the stability of the chlortetracycline hydrochloride soluble powder after being dissolved in water is improved;
4. the clinical water quality is complex, and the anhydrous sodium dihydrogen phosphate and the anhydrous disodium hydrogen phosphate prepared by the invention are provided with an acid-base buffer system according to the proportion of 1:1, so that the pH value of the buffer system is close to neutral, and the tolerance of the chlortetracycline hydrochloride soluble powder to water with different clinical pH values is enhanced.
Detailed Description
In order that the invention may be readily understood, a more particular description of the invention will be rendered by reference to specific embodiments that are illustrated in the appended drawings. 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 herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Materials, reagents, equipment sources:
the materials and equipment used in the embodiment are all commercially available sources unless specified; the experimental methods are all routine experimental methods in the field unless specified.
Example 1 Aureomycin hydrochloride soluble powder suitable for Complex Water quality and preparation thereof
The formula comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 4.5kg, poloxamer 188 1.2kg, vitamin C0.3 kg, dimercaptoethyl glycine 0.25kg, anhydrous sodium dihydrogen phosphate 3kg, anhydrous disodium hydrogen phosphate 3kg and anhydrous glucose 67.75kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
Example 2 Aureomycin hydrochloride soluble powder adapting to Complex Water quality and preparation thereof
The formula comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 3kg, poloxamer 1880.5kg, vitamin C0.1 kg, dimercaptoethylglycine 0.05kg, anhydrous sodium dihydrogen phosphate 2kg, anhydrous disodium hydrogen phosphate 2kg and anhydrous glucose 72.35kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing anhydrous glucose into a three-dimensional mixer, and continuously mixing for 15 minutes to obtain the chlortetracycline hydrochloride soluble powder.
Example 3 Aureomycin hydrochloride soluble powder adapted to Complex Water quality and preparation thereof
The formula comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 7kg, poloxamer 188 2kg, vitamin C0.5 kg, dimercaptoethylglycine 0.5kg, anhydrous sodium dihydrogen phosphate 7kg, anhydrous disodium hydrogen phosphate 7kg and anhydrous glucose 56kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing 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 comprises the following components: aureomycin hydrochloride 20kg, poloxamer 188 1.2kg, vitamin C0.3 kg, dimercaptoethylglycine 0.25kg, anhydrous sodium dihydrogen phosphate 3kg, anhydrous disodium hydrogen phosphate 3kg and anhydrous glucose 72.25kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, pouring aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate, anhydrous disodium hydrogen phosphate, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s3, throwing 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 phospholipid was added, nor was there a spray drying operation.
Comparative example 2
The formula comprises the following components: aureomycin hydrochloride 20kg, lecithin 4.5kg, poloxamer 188 1.2kg, vitamin C0.3 kg, dimercaptoethyl glycine 0.25kg, anhydrous sodium dihydrogen phosphate 3kg, anhydrous disodium hydrogen phosphate 3kg and anhydrous glucose 67.75kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, dissolving lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing 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 soybean phospholipid was changed to lecithin.
Comparative example 3
The formula comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 4.5kg, poloxamer 188 1.2kg, vitamin C0.3 kg, dimercaptoethyl glycine 0.25kg, anhydrous sodium dihydrogen phosphate 4kg, anhydrous disodium hydrogen phosphate 2kg, anhydrous glucose 67.75kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous glucose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol solution with the concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing 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 comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 4.5kg, poloxamer 188 1.2kg, vitamin C0.3 kg, sodium citrate 0.25kg, anhydrous sodium dihydrogen phosphate 3kg, anhydrous disodium hydrogen phosphate 3kg and anhydrous glucose 67.75kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, vitamin C, sodium citrate and anhydrous dextrose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C and sodium citrate into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing 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 comprises the following components: aureomycin hydrochloride 20kg, soybean lecithin 4.5kg, poloxamer 188 1.2kg, dimercaptoethylglycine 0.25kg, anhydrous sodium dihydrogen phosphate 3kg, anhydrous disodium hydrogen phosphate 3kg and anhydrous glucose 68.05kg
The preparation process comprises the following steps:
s1, respectively weighing the raw materials according to the formula amount; wherein poloxamer 188, dimercaptoethylglycine and anhydrous dextrose are screened by a 100-mesh screen for later use;
s2, dissolving soybean lecithin in an ethanol water solution with the volume percentage concentration of 30%, adding aureomycin hydrochloride, anhydrous sodium dihydrogen phosphate and anhydrous disodium hydrogen phosphate, and stirring to dissolve to obtain a mixed solution;
s3, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, dimercaptoethyl glycine and the dimercaptoethyl glycine into a three-dimensional mixer, and mixing for 15 minutes;
s4, throwing 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 was added.
Test example I stability test of aureomycin hydrochloride soluble powder
(1) Test sample: examples 1-3, comparative examples 1-2, chlortetracycline hydrochloride soluble powder
(2) The test method comprises the following steps:
placing the chlortetracycline hydrochloride soluble powder sample under the conditions of high temperature (60 ℃) and high humidity (relative humidity 95% +/-5%), and sampling at 5 days and 10 days for detection according to quality standards;
placing a chlortetracycline hydrochloride soluble powder sample at a temperature of 40+/-2 ℃ and a humidity of 75% +/-5% for 6 months, performing an acceleration stability test, and respectively sampling at 1 st month, 2 months, 3 months and 6 months for detection according to quality standards;
(3) Test results
TABLE 1 stability test results of soluble aureomycin hydrochloride powder
As can be seen from the data in Table 1, in the high-temperature and high-humidity environment for 10 days and in the accelerated test for 6 months, all detection indexes of the chlortetracycline hydrochloride soluble powder prepared in the embodiment 1-3 are in a qualified range, and compared with the 0 th month, the change is not obvious, so that the compatibility of prescription materials of the chlortetracycline hydrochloride soluble powder is good and relatively stable, wherein the change index of the chlortetracycline hydrochloride soluble powder prepared in the embodiment 1 is the smallest, and the chlortetracycline hydrochloride soluble powder is the best embodiment of the invention; in comparative example 1, no soybean lecithin was added, and liposome powder could not be formed after spray drying, so that the prepared chlortetracycline hydrochloride soluble powder had poor stability, and was rapidly discolored and agglomerated in high-temperature, high-humidity and accelerated environments; comparative example 2 has reduced stability due to the replacement of soybean lecithin with lecithin, and is prone to discoloration and caking even after prolonged periods of time in high temperature, high humidity and accelerated environments.
Test example II, content stability test of soluble aureomycin hydrochloride powder dissolved in water of different hardness
(1) Test sample: the 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:
softened water (hardness standard <150 mg/L);
medium hardness water (hardness standard 150-300 mg/L): 0.152 Dissolving anhydrous magnesium chloride and 0.0695g of crystalline magnesium chloride with water, and then fixing the volume to 1000 ml;
high hardness water (hardness standard 300-450 mg/L): 0.304 Dissolving anhydrous magnesium chloride and 0.139g of crystalline magnesium chloride with water, and then fixing the volume to 1000 mL;
clinical water 1 is tap water; clinical water 2 is river water;
the test process comprises the following steps: taking the chlortetracycline hydrochloride soluble powder prepared in the examples 1-3 and the comparative examples 4-5, respectively 0.2 and kg, precisely weighing, respectively dissolving with water with different hardness and clinical water 1-2, fixing the volume to 100 mL with water with corresponding hardness, respectively precisely taking 20 mu L of water solution with the 0 th, 4 th, 8 th, 12 th and 24 th h th 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 the chlortetracycline hydrochloride in the solution according to an external standard method.
(3) Test results: the results are shown in the following table:
table 2, content of chlortetracycline hydrochloride soluble powder in water of different hardness and clinical water.
As can be seen from the data in Table 2, the soluble aureomycin hydrochloride powder samples prepared in examples 1-3 of the present invention are dissolved in water of different hardness and clinical water quality, the marked content of the solution is not obviously changed, and the soluble aureomycin hydrochloride powder sample is still relatively stable after 24 hours; wherein the variation of example 1 is the least obvious and is the best mode of practicing 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 is changed into sodium citrate because dimercaptoethyl glycine has no better chelating effect with metal ions such as calcium, magnesium and the like in water, and precipitation occur along with the extension of time after dissolution, so that the marked content is obviously reduced and the stability is poor; the chlortetracycline hydrochloride soluble powder prepared in comparative example 5 has no vitamin C, no vitamin C-assisted dimercaptoethyl glycine, and the oxidation resistance of the chlortetracycline hydrochloride soluble powder and the chelation effect of the dimercaptoethyl glycine with metal ions such as calcium and magnesium in water are reduced, so that the interference of chlortetracycline hydrochloride molecules by the metal ions cannot be avoided, the stability of the sample after dissolution in water, particularly in clinical water quality 1-2, is obviously reduced, and the mark content is obviously reduced along with the extension of time.
Test example III content stability test of soluble powder of aureomycin hydrochloride after dissolution in aqueous solutions of different pH values
(1) Test sample: the chlortetracycline hydrochloride soluble powder 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 regulating the pH value to 5.0+/-0.2 by using a hydrochloric acid solution;
taking a proper amount of purified water, and regulating the pH value to 9.0+/-0.2 by using a sodium hydroxide solution;
taking the chlortetracycline hydrochloride soluble powder prepared in the examples 1-3 and the comparative example 3, respectively 0.2 kg, precisely weighing, respectively dissolving with water with different pH values, fixing the volume to 100 mL with water with corresponding pH values, respectively precisely taking 20 mu L of water solution of the 0 th, 4 th, 8 th, 12 th and 24 h th after dissolving, filtering with a 0.45 mu m filter membrane, injecting into a liquid chromatograph, and recording a chromatogram; calculating the content of chlortetracycline hydrochloride in the solution according to an external standard method;
(3) Test results: the results are shown in the following table:
TABLE 3 stability of the content of soluble powder of aureomycin hydrochloride in Water of different pH values
As can be seen from the data in Table 3, in the observation period of 24 h after the dissolution in the aqueous solutions with different pH values, the marked content of the aqueous solutions containing the chlortetracycline hydrochloride soluble powder prepared in the examples 1-3 of the invention has insignificant changes, is relatively stable, has relatively strong tolerance to water with different clinical pH values, wherein the content of the example 1 has least significant changes, and is the best example of the invention; the ratio of anhydrous sodium dihydrogen phosphate to anhydrous disodium hydrogen phosphate of the chlortetracycline hydrochloride soluble powder prepared in the comparative example 3 is 4:2, and the pH value of a buffer system is not close to neutrality, so that the tolerance of the chlortetracycline hydrochloride soluble powder to the pH value is affected, the marked content in an aqueous solution with the pH value of 9.0 is obviously reduced, and the marked content is reduced by 85.4%.
The technical principle of the present invention is described above in connection with the specific embodiments. The description is made for the purpose of illustrating the general principles of the invention and should not be taken in any way as limiting the scope of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein, without departing from the spirit and scope of the invention as defined by the claims.
Claims (8)
1. An aureomycin hydrochloride soluble powder suitable for complex water quality, which is characterized by comprising the following components: according to the weight portions, 20 portions of chlortetracycline hydrochloride, 3 to 7 portions of soybean phosphatide, 0.5 to 2 portions of solubilizer, 0.1 to 0.5 portion of vitamin C, 0.05 to 0.5 portion of dimercaptoethyl glycine, 2 to 7 portions of anhydrous sodium dihydrogen phosphate, 2 to 7 portions of anhydrous disodium hydrogen phosphate and 56 to 72.35 portions of anhydrous glucose;
the mass ratio of the anhydrous sodium dihydrogen phosphate to the anhydrous disodium hydrogen phosphate is 1:1;
the solubilizer is poloxamer 188;
the preparation method of the chlortetracycline hydrochloride soluble powder adapting to complex water quality comprises the following steps:
s1, respectively weighing the raw materials according to the prescription amount for standby;
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, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C, dimercaptoethyl glycine and the mixture into a three-dimensional mixer for mixing;
s4, throwing anhydrous glucose into a three-dimensional mixer, and mixing to obtain the chlortetracycline hydrochloride soluble powder.
2. The soluble aureomycin hydrochloride powder suitable for complex water quality according to claim 1, wherein the mass ratio of the vitamin C to the dimercaptoethyl glycine is (1-10): 1.
3. The soluble aureomycin hydrochloride powder adapted to complex water quality according to claim 1, comprising: the pharmaceutical composition comprises, by weight, 20 parts of aureomycin hydrochloride, 4.5 parts of soybean phospholipids, 1.2 parts of solubilizer, 0.3 part of vitamin C, 0.25 part of dimercaptoethyl glycine, 3 parts of anhydrous sodium dihydrogen phosphate, 3 parts of anhydrous disodium hydrogen phosphate and 67.75 parts of anhydrous glucose.
4. A method for preparing the aureomycin hydrochloride soluble powder adapting to complex water quality as claimed in any one of claims 1 to 3, comprising the following steps:
s1, respectively weighing the raw materials according to the prescription amount for standby;
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, spraying and drying the mixed solution, and then adding the mixed solution, poloxamer 188, vitamin C, dimercaptoethyl glycine and the mixture into a three-dimensional mixer for mixing;
s4, throwing anhydrous glucose into a three-dimensional mixer, and mixing to obtain the chlortetracycline hydrochloride soluble powder.
5. The method for preparing the chlortetracycline hydrochloride soluble powder suitable for complex water quality as defined in claim 4, wherein the raw materials of poloxamer 188, vitamin C, dimercaptoethyl glycine and anhydrous dextrose in the step S1 are screened by a 100-mesh screen.
6. The method for preparing the chlortetracycline hydrochloride soluble powder adapting to complex water quality as defined in claim 4, wherein the solvent in the step S2 is an ethanol aqueous solution with a volume percentage concentration of 30%.
7. The method for preparing the chlortetracycline hydrochloride soluble powder adaptive to complex water quality as defined in claim 4, wherein the mixing time of the step S3 is 15 minutes.
8. The method for preparing the soluble aureomycin hydrochloride powder according to claim 4, wherein the mixing time in the 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 |
| 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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