CN114425037B - Compound hydroxychlorozamine suspension and preparation method thereof - Google Patents
Compound hydroxychlorozamine suspension 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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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
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
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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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- 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 belongs to the technical field of veterinary medicines, and discloses a compound hydroxychlorozamine suspension and a preparation method thereof. The invention provides a compound hydroxychlorozamine suspension, which comprises the following raw materials: the compound hydroxychlorozamine suspension with the main component content of 95-105%, the single impurity content of less than 0.5%, the total impurity content of less than 1%, high purity, no obvious change under high temperature and illumination conditions, strong stability and excellent redispersibility is obtained by the combination of the raw materials. The invention also provides a preparation method of the compound hydroxychlorozamine suspension, which has low preparation cost, few raw material types and simple preparation process, and is suitable for popularization and application.
Description
Technical Field
The invention relates to the technical field of veterinary medicines, in particular to a compound hydroxychlorozamine suspension and a preparation method thereof.
Background
The hydroxychlorozamine is also known as chlorohydrin, hydroxychloro Liu Benan and the like, and the chemical name is 2,3, 5-trichloro-N- (3, 5-dichloro-2-hydroxyphenyl) -6-hydroxybenzoamide, is a salicylic acid aniline insect repellent, is an oxidative phosphorylation uncoupler and is mainly used for treating Fasciola hepatica (Fasciola), ascarid and tapeworm infections of animals such as cattle and sheep. It can reduce the synthesis amount of Adenosine Triphosphate (ATP) in insects, thereby leading to death of insects due to energy metabolism disorder. The action mechanism is mainly to inhibit the oxidative phosphorylation process in the parasite, reduce the generation of ATP, reduce the glycogen content and accumulate succinic acid, thereby affecting the energy metabolism process of the parasite and leading the parasite to die.
The hydroxychlorozamine belongs to insoluble substances, and at present, the hydroxychlorozamine suspension has more auxiliary materials during preparation, high cost, easy generation of bubbles during use and poor redispersion performance. Therefore, a hydroxychlorozamine suspension which has low development cost, uses few types of raw materials, and has excellent redispersibility is highly demanded in the art.
Disclosure of Invention
In view of the above, the invention provides a compound hydroxychlorozamine suspension and a preparation method thereof, which solve the problems of more auxiliary materials, high cost, easy generation of bubbles during use and poor redispersion performance of the existing hydroxychlorozamine suspension.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides a compound hydroxychlorozamine suspension, which comprises the following components in every 100L of compound hydroxychlorozamine suspension:
the invention also provides a preparation method of the compound hydroxychlorozamine suspension, which comprises the following steps:
(1) Refining the hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon yellow;
(2) Mixing refined xanthan gum with 40-60 vt% water, and swelling to obtain a mixed xanthan gum solution; adding refined sodium bisulphite, lemon yellow and levamisole hydrochloride raw material medicines to obtain a first solution;
(3) Mixing the hydroxychlorozamide crude drug with propylene glycol to obtain a second solution;
(4) And mixing the first solution, the second solution, the benzoic acid and the residual water to obtain the compound oxychlorozamine suspension.
Preferably, in the step (1), the particle size of the oxychlorozamine crude drug, the levamisole hydrochloride crude drug, the xanthan gum, the sodium bisulphite, the benzoic acid and the lemon yellow is independently not less than 80 meshes.
Preferably, in the step (2), the mixing time is 20 to 24 hours; the stirring swelling speed is 200-300 r/min, and the time is 20-40 min.
Preferably, in the step (4), the first solution, the second solution, the benzoic acid and the remaining water are mixed in the following manner: the first solution and the second solution are mixed, and benzoic acid and the remaining water are added.
Preferably, the first solution and the second solution are mixed in the following manner: adding the second solution to the first solution under stirring; the stirring speed is 100-200 r/min.
The invention also provides another preparation method of the compound hydroxychlorozamine suspension, which comprises the following steps:
(1) The preparation method comprises the steps of (1) mixing a hydroxychlorozamide crude drug, a levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon Huang Xihua;
(2) Mixing 40-60 vt percent of propylene glycol with water to obtain propylene glycol solution, adding refined xanthan gum, sodium bisulphite, benzoic acid and lemon yellow for dispersion, and sieving to obtain a first mixed solution;
(3) Mixing the rest propylene glycol with water to obtain propylene glycol solution, and adding refined hydroxychlorozamide crude drug and levamisole hydrochloride crude drug to obtain a second mixed solution;
(4) And mixing the first mixed solution and the second mixed solution to obtain the compound hydroxychlorozamine suspension.
Preferably, in the step (1), the particle sizes of the refined hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, the xanthan gum, the sodium bisulfite, the benzoic acid and the lemon yellow are independently less than or equal to 1 μm.
Preferably, in the step (2), the screen used for the sieving is a 80-100 mesh screen.
Preferably, in the step (2) and the step (3), the concentration of the propylene glycol solution is independently 40 to 60%.
Compared with the prior art, the invention has the following beneficial effects:
the main component content of the compound hydroxychlorozamine suspension is 95-105%, the single impurity content is less than 0.5%, the total impurity content is less than 1%, the purity is high, no obvious change is caused under high temperature and illumination conditions, the stability is strong, and the redispersibility is excellent;
the preparation cost of the compound hydroxychlorozamine suspension is low, the variety of used raw materials is few, the preparation process is simple, and the compound hydroxychlorozamine suspension is suitable for popularization and application.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only embodiments of the present invention, and that other drawings can be obtained according to the provided drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the particle size distribution of sample 1 obtained in example 1 of the present invention;
FIG. 2 is a graph showing the particle size distribution of sample 2 obtained in example 2 of the present invention;
FIG. 3 is a graph showing the particle size distribution of sample 3 obtained in example 3 of the present invention;
FIG. 4 is a content measurement chromatogram of sample 1 obtained in example 1 of the present invention;
FIG. 5 is a content measurement chromatogram of sample 2 obtained in example 2 of the present invention;
FIG. 6 is a content measurement chromatogram of sample 3 obtained in example 3 of the present invention;
FIG. 7 is a chromatogram of the measurement of the related substances of the blank auxiliary material of the sample obtained in example 1 of the present invention;
FIG. 8 is a chromatogram of the measurement of a substance of sample 1 obtained in example 1 of the present invention;
FIG. 9 is a chromatogram of the measurement of the related substances of the blank auxiliary material of the sample obtained in example 2 of the present invention;
FIG. 10 is a chromatogram of the measurement of a substance of sample 2 obtained in example 2 of the present invention;
FIG. 11 is a chromatogram of the measurement of related substances of the blank auxiliary material of the sample obtained in example 3 of the present invention;
FIG. 12 is a chromatogram of the sample 3 obtained in example 3 according to the present invention.
Detailed Description
The invention provides a compound hydroxychlorozamine suspension, which comprises the following components in every 100L of compound hydroxychlorozamine suspension:
the invention also provides a preparation method of the compound hydroxychlorozamine suspension, which comprises the following steps:
(1) Refining the hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon yellow;
(2) Mixing refined xanthan gum with 40-60 vt% water, and swelling to obtain a mixed xanthan gum solution; adding refined sodium bisulphite, lemon yellow and levamisole hydrochloride raw material medicines to obtain a first solution;
(3) Mixing the hydroxychlorozamide crude drug with propylene glycol to obtain a second solution;
(4) And mixing the first solution, the second solution, the benzoic acid and the residual water to obtain the compound oxychlorozamine suspension.
In the present invention, in the step (1), the particle size number of the oxychlorozamine bulk drug, the levamisole hydrochloride bulk drug, the xanthan gum, the sodium bisulphite, the benzoic acid and the lemon yellow is preferably not less than 80 meshes, and more preferably not less than 100 meshes.
In the present invention, in the step (2), the swelling of the refined xanthan gum is preferably performed with 45 to 55vt% water, and more preferably with 50vt% water; the mixing time is preferably 20 to 24 hours, more preferably 21.5 to 23 hours; the stirring swelling speed is preferably 200 to 300r/min, more preferably 220 to 280r/min; the stirring and swelling time is preferably 20 to 40 minutes, more preferably 25 to 35 minutes.
In the present invention, in the step (4), the mixing manner of the first solution, the second solution, the benzoic acid and the residual water is: the first solution and the second solution are mixed, and benzoic acid and the remaining water are added.
In the invention, the first solution and the second solution are mixed in the following way: adding the second solution to the first solution under stirring; the stirring speed is preferably 100 to 200r/min, and more preferably 125 to 170r/min.
The invention also provides another preparation method of the compound hydroxychlorozamine suspension, which comprises the following steps:
(1) The preparation method comprises the steps of (1) mixing a hydroxychlorozamide crude drug, a levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon Huang Xihua;
(2) Mixing 40-60 vt percent of propylene glycol with water to obtain propylene glycol solution, adding refined xanthan gum, sodium bisulphite, benzoic acid and lemon yellow for dispersion, and sieving to obtain a first mixed solution;
(3) Mixing the rest propylene glycol with water to obtain propylene glycol solution, and adding refined hydroxychlorozamide crude drug and levamisole hydrochloride crude drug to obtain a second mixed solution;
(4) And mixing the first mixed solution and the second mixed solution to obtain the compound hydroxychlorozamine suspension.
In the present invention, in the step (1), the particle sizes of the refined hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, the xanthan gum, the sodium bisulphite, the benzoic acid and the lemon yellow are preferably not more than 1 μm, and more preferably not more than 0.8 μm independently.
In the present invention, in the step (2), the propylene glycol solution is preferably mixed with water in an amount of 45 to 55vt%, and more preferably mixed with water in an amount of 50 vt%; the screen used for the sieving is preferably a 80-100 mesh screen, more preferably 80 mesh screen.
In the present invention, the concentration of the propylene glycol solution in the step (2) and the step (3) is independently preferably 40 to 60%, more preferably 45 to 55%.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
The effective components and auxiliary materials are as follows:
the preparation process comprises the following steps:
grinding the raw materials and the auxiliary materials respectively by a ball mill, and sieving with a 80-mesh sieve for standby. Soaking xanthan gum in distilled water with a half of the prescription amount in advance for 22 hours to make the xanthan gum primarily swell, stirring at a rotating speed of 250r/min for 30 minutes to make the xanthan gum fully swell, sequentially and slowly adding sodium bisulphite, lemon yellow and levamisole hydrochloride into a container, and continuously stirring until the mixture is fully dispersed to obtain a first solution; adding propylene glycol with a prescription amount into a container, adding hydroxychlorozamide, stirring to fully moisten the mixture to obtain a second solution, regulating the rotating speed of an electric stirrer to 150r/min, slowly adding the second solution into the first solution under stirring, adding benzoic acid after uniformly stirring, and stirring after distilled water is subjected to constant volume to obtain a sample 1.
Preparing blank auxiliary materials of a sample: the preparation of the sample 1 is different from that of the hydroxychlorozamide crude drug and the levamisole hydrochloride crude drug.
Example 2
The effective components and auxiliary materials are as follows:
the preparation process comprises the following steps:
grinding the raw materials and the auxiliary materials respectively by a ball mill, and sieving with a 100-mesh sieve for standby. Soaking xanthan gum in distilled water with a half of the prescription amount for 24 hours in advance to make the xanthan gum primarily swell, stirring at a rotating speed of 280r/min for 30 minutes to make the xanthan gum fully swell, sequentially and slowly adding sodium bisulphite, lemon yellow and levamisole hydrochloride into a container, and continuously stirring until the mixture is fully dispersed to obtain a first solution; adding propylene glycol with a prescription amount into a container, adding hydroxychlorozamide, stirring to fully moisten the mixture to obtain a second solution, regulating the rotating speed of an electric stirrer to 165r/min, slowly adding the second solution into the first solution under stirring, adding benzoic acid after uniformly stirring, and stirring after distilled water is fixed in volume to obtain a sample 2.
Preparing blank auxiliary materials of a sample: the preparation of the sample 2 is different from that of the hydroxychlorozamide crude drug and the levamisole hydrochloride crude drug.
Example 3
The effective components and auxiliary materials are as follows:
the preparation process comprises the following steps:
carrying out air flow superfine grinding on the raw material medicines and auxiliary materials until the particle size is smaller than 1 mu m, putting the propylene glycol with the prescription amount in a container for standby, adding water to dilute the propylene glycol into a 50% propylene glycol aqueous solution, equally dividing the 50% propylene glycol aqueous solution into two parts, adding the auxiliary materials with the prescription amount into one part, uniformly stirring the auxiliary materials, sieving the auxiliary materials with a 80-mesh sieve after colloid milling to obtain a first solution, adding the hydroxychlorozamide and levamisole hydrochloride into the other part, uniformly stirring the other part to obtain a second solution, uniformly mixing the first solution and the second solution, and then fixing the volume and uniformly stirring the first solution and the second solution to obtain the sample 3.
Preparing blank auxiliary materials of a sample: the preparation of the sample 3 is different from that of the hydroxychlorozamide crude drug and the levamisole hydrochloride crude drug.
The three samples obtained in examples 1 to 3 were evaluated for quality as follows:
1. appearance and pH
The prepared samples 1-3 are all suspensions which are bright yellow, uniform in color, sticky and free of the Tyndall effect, layering can occur after the suspensions are kept for a long time, supernatant is yellow and transparent, and sediment with a pale yellow lower layer can be restored to a uniform system after the suspensions are gently shaken. The pH of samples 1 to 3 was measured to be 4.43, 4.37 and 4.35, respectively, and the average pH was 4.38.
2. Volume ratio of sedimentation and number of redispersions
As shown in Table 1, samples 1 to 3 had a sedimentation volume ratio of more than 0.9 and good redispersibility.
TABLE 1 sedimentation volume ratio and redispersibility measurement results
| Sample of | Sedimentation volume ratio | Number of redispersions |
| 1 | 0.99 | 2 |
| 2 | 1 | 1 |
| 3 | 0.99 | 1 |
3. Particle size measurement results
The particle sizes and distributions of the samples 1 to 3 were as shown in FIGS. 1 to 3, and the average particle sizes were 3514nm, 3421nm and 3238nm, respectively, each smaller than 10. Mu.m. The particle size distribution of the compound oxychlorozamine suspension obtained by the invention is uniform.
4. Content determination
The measurement was performed by high performance liquid chromatography.
Chromatographic conditions and system suitability test: octadecylsilane chemically bonded silica is used as packing material (ZORBAX SB-C18, 150X4.6 mm,5 μm or equivalent chromatography column); gradient elution was performed using 0.1% phosphoric acid-7 mM disodium hydrogen phosphate aqueous solution as mobile phase A and methanol as mobile phase B according to Table 2 below; the flow rate is 0.7ml per minute; the detection wavelength is 230mn; the column temperature is 35 ℃; the number of theoretical plates is not lower than 2500 according to the peak of hydroxychlorozamine and levamisole hydrochloride.
TABLE 2 HPLC elution gradient
| Time (min) | Phase A (%) | Phase B (%) |
| 0 | 70 | 30 |
| 8 | 10 | 90 |
| 13 | 10 | 90 |
| 15 | 70 | 30 |
| 18 | 70 | 30 |
Assay: precisely weighing 60mg of oxychlorozamine reference substance, 30mg of levamisole hydrochloride reference substance, placing in a 100mL measuring flask, ultrasonically dissolving with 80% methanol water, diluting to scale, shaking uniformly, precisely weighing 1mL, placing in a 10mL measuring flask, and diluting with 80% methanol water to scale to obtain reference substance solution; taking a proper amount of the product (about 60mg corresponding to hydroxychlorozamide and 30mg of levamisole hydrochloride), precisely weighing, placing in a 100mL volumetric flask, adding 80% methanol water for dissolution and dilution to scale, fully mixing uniformly, centrifuging, precisely weighing 1mL of supernatant, placing in a 10mL volumetric flask, diluting to scale with 80% methanol water, shaking uniformly, and taking as a sample solution; precisely measuring 5 μl of each of the control solution and the sample solution, respectively injecting into a liquid chromatograph, and recording the chromatograms. And calculating according to an external standard method and peak area to obtain the product.
The content detection results of the samples 1-3 are shown in Table 3, and the corresponding maps are shown in fig. 4-6, which shows that the content of the main components of the compound oxychlorozamine suspension obtained by the invention is 95-105%, and the compound oxychlorozamine suspension meets the requirements.
TABLE 3 sample content determination results
5. Related substances
The measurement was performed by high performance liquid chromatography.
Chromatographic conditions and system suitability test: octadecylsilane chemically bonded silica is used as a packing material (poroshall EC-C18, 150X4.6 mm,2.7 μm or equivalent chromatography column); gradient elution was performed using 0.5% ammonium dihydrogen phosphate aqueous solution (1M NaOH solution to adjust pH to 6.6) as mobile phase a and methanol as mobile phase B, as shown in table 4 below; the flow rate is 0.7ml per minute; the detection wavelength is 230mn; the column temperature is 35 ℃; the number of theoretical plates is not lower than 2500 according to the peak of hydroxychlorozamine and levamisole hydrochloride.
TABLE 4 HPLC elution gradient
| Time (min) | Phase A (%) | Phase B (%) |
| 0 | 50 | 50 |
| 12 | 50 | 50 |
| 13 | 30 | 70 |
| 22 | 30 | 70 |
| 22.1 | 50 | 50 |
| 60 | 50 | 50 |
Assay: taking the compound hydroxychlorozamine suspension (the dosage of the compound hydroxychlorozamine suspension is equal to 60mg of hydroxychlorozamine and 30mg of levamisole hydrochloride), precisely weighing, putting into a 100mL measuring flask, adding 20mL of pure water to disperse the mixture, adding methanol to carry out ultrasonic dissolution and fully and uniformly mixing, diluting to a scale with methanol, shaking uniformly, centrifuging, and taking supernatant as a sample solution; 1mL of the sample solution is precisely measured, placed in a 100mL measuring flask, diluted to a scale by a mobile phase, and shaken uniformly to serve as a control solution. Precisely measuring 10 mu L of each of the control solution and the sample solution, respectively injecting into a liquid chromatograph, and recording the chromatogram till 3 times of the retention time of the main component peak. The main component self-comparison method without correction factor is used for calculating the peak area, the single impurity is less than 0.5%, the total impurity amount is less than 1.0%, and the chromatographic peak which is smaller than 0.05 times of the main peak area of the control solution in the chromatogram of the sample solution is ignored.
The detection results of related substances of samples 1 to 3 are shown in Table 5, and the corresponding maps are shown in fig. 7 to 9, which show that the single impurity content of the compound oxychlorozamine suspension obtained by the invention is less than 0.5%, the total impurity content is less than 1.0%, and the compound oxychlorozamine suspension meets the requirements.
TABLE 5 detection results of related substances
6. Stability of
Table 6 high temperature test
TABLE 7 light test
The influence factor tests are carried out on the samples 1-3, and the test results show that each index of the compound hydroxychlorozamine suspension has no obvious change under the conditions of high temperature and illumination, thus showing that the compound hydroxychlorozamine suspension obtained by the invention has stable properties.
The three samples obtained in examples 1 to 3 were subjected to clinical trials, and the results were as follows:
the same type of products (hydroxychlorozate (30 mg/mL) and levamisole hydrochloride (15 mg/mL) as main components) sold abroad were selected as drug control groups, and the clinical test was as follows:
1. experimental animal screening
And selecting sheep with clinical symptoms of diarrhea, emaciation, dyspepsia, listlessness and slow response to external stimulus, and further detecting faecal eggs to determine positive cases of nematode and fasciola hepatica infection.
2. Experimental method
Through positive case screening, 125 sheep infected with fasciola hepatica and nematode enter clinical test, the tested sheep are randomly divided into 5 groups, namely a low dose group, a medium dose group and a high dose group of the compound hydroxychlorozamide suspension, a drug control group and a blank control group, and the number of tested animals is 20, 45, 20 and 20 respectively. The administration amounts of the test groups are 7.5mg/kg.BW, 15mg/kg.BW and 30mg/kg.BW according to the hydroxychlorozate; the drug control group is a foreign preparation of the same type, the dosage is 15 mg/kg/BW according to the hydroxychlorozate, and the blank group is not treated by the drug. The administration mode is single oral administration. As shown in table 1.
Table 8 test drug groupings and dosages
3. Result determination
At 3d,7d,14d,21d,28d and 56d after administration, the therapeutic effect of the oxychloroligation, levamisole hydrochloride suspension was evaluated in terms of egg reduction rate (FECR) and egg negative conversion rate (CPCR) according to changes in fecal egg numbers; the formula used is as follows:
FECR% = (pre-dose EPG-post-dose EPG)/pre-dose EPG x 100%
CPCR% = number of eggs to negative animals/number of experimental animals×100%
The test group showed a reduction rate of more than 90% of eggs, which was significantly different from the blank group (P < 0.05), and was considered to be pharmaceutically effective.
4. Analysis of results
Table 9 average number of eggs per gram faeces (EPG value) at different stages of the experimental group sheep and statistics after 56d administration
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Note that: * Mean that the difference between the groups compared with the blank group is very significant p <0.01
The results show that compared with the control medicine, the compound hydroxychlorozamine suspension has obviously better treatment effect on nematodes and flukes than the similar compound levamisole suspension oral liquid abroad. The cure rate of the medium-dose group and the high-dose group of the compound suspension obtained by the invention on sheep infected with nematodes and flukes reaches more than 95 percent, which is obviously better than 92.13 percent of foreign similar preparations (the main components of the hydroxychlorozamide (30 mg/mL) and the levamisole hydrochloride (15 mg/mL)).
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (9)
1. The compound hydroxychlorozamine suspension is characterized by comprising the following components in every 100L of compound hydroxychlorozamine suspension:
5.5-6.5 kg of hydroxychlorozamine bulk drug
2.7-3 kg of levamisole hydrochloride bulk drug
340-360 g of xanthan gum
Propylene glycol 8-10L
180-220 g of sodium bisulphite
90-110 g of benzoic acid
Lemon yellow 8-12 g
Purified water was made up to 100L;
the preparation method of the compound oxychlorozamine suspension comprises the following steps:
(1) Refining the hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon yellow;
(2) Mixing refined xanthan gum with 40-60 vt% of water, and swelling to obtain a xanthan gum mixed solution; adding refined sodium bisulphite, lemon yellow and levamisole hydrochloride raw material medicines to obtain a first solution;
(3) Mixing the hydroxychlorozamide crude drug with propylene glycol to obtain a second solution;
(4) Mixing the first solution, the second solution, benzoic acid and the rest water to obtain a compound oxychlorozamine suspension;
in the step (2), the mixing time is 20-24 hours; the stirring swelling speed is 200-300 r/min, and the time is 20-40 min.
2. The method for preparing the compound hydroxychlorozamine suspension, according to claim 1, is characterized by comprising the following steps:
(1) Refining the hydroxychlorozamide crude drug, the levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon yellow;
(2) Mixing refined xanthan gum with 40-60 vt% of water, and swelling to obtain a xanthan gum mixed solution; adding refined sodium bisulphite, lemon yellow and levamisole hydrochloride raw material medicines to obtain a first solution;
(3) Mixing the hydroxychlorozamide crude drug with propylene glycol to obtain a second solution;
(4) Mixing the first solution, the second solution, benzoic acid and the rest water to obtain a compound oxychlorozamine suspension;
in the step (2), the mixing time is 20-24 hours; the stirring swelling speed is 200-300 r/min, and the time is 20-40 min.
3. The method for preparing the compound hydroxychlorozamine suspension according to claim 2, wherein in the step (1), the particle size and the number of the hydroxychlorozamine bulk drug, the levamisole hydrochloride bulk drug, the xanthan gum, the sodium bisulphite, the benzoic acid and the lemon yellow are independently not less than 80 meshes.
4. The method for preparing the compound oxychlorozamine suspension according to claim 2, wherein in the step (4), the mixing mode of the first solution, the second solution, the benzoic acid and the residual water is as follows: the first solution and the second solution are mixed, and benzoic acid and the remaining water are added.
5. The method for preparing the compound oxychlorozamine suspension according to claim 2 or 3, wherein the first solution and the second solution are mixed in the following manner: adding the second solution to the first solution under stirring; the stirring speed is 100-200 r/min.
6. The method for preparing the compound hydroxychlorozamine suspension, according to claim 1, is characterized by comprising the following steps:
(1) The preparation method comprises the steps of (1) mixing a hydroxychlorozamide crude drug, a levamisole hydrochloride crude drug, xanthan gum, sodium bisulfite, benzoic acid and lemon Huang Xihua;
(2) Mixing 40-60 vt percent of propylene glycol with water to obtain a propylene glycol solution, adding refined xanthan gum, sodium bisulphite, benzoic acid and lemon yellow for dispersion, and sieving to obtain a first mixed solution;
(3) Mixing the rest propylene glycol with water to obtain propylene glycol solution, and adding refined hydroxychlorozamide crude drug and levamisole hydrochloride crude drug to obtain a second mixed solution;
(4) And mixing the first mixed solution and the second mixed solution to obtain the compound hydroxychlorozamine suspension.
7. The method for preparing a compound hydroxychlorozamine suspension according to claim 6, wherein in the step (1), the particle size of the refined hydroxychlorozamine bulk drug, the levamisole hydrochloride bulk drug, the xanthan gum, the sodium bisulphite, the benzoic acid and the lemon yellow is independently less than or equal to 1 μm.
8. The method for preparing a compound oxychlorozamine suspension according to claim 7, wherein in the step (2), a sieve for sieving is a 80-100 mesh sieve.
9. The method for preparing a compound oxychlorozamine suspension according to any one of claims 6 to 8, wherein in the step (2) and the step (3), the concentration of the propylene glycol solution is independently 40 to 60%.
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