CN105126073B - A kind of high stability Nosiheptide solution and preparation method thereof - Google Patents
A kind of high stability Nosiheptide solution and preparation method thereof Download PDFInfo
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- CN105126073B CN105126073B CN201510552780.5A CN201510552780A CN105126073B CN 105126073 B CN105126073 B CN 105126073B CN 201510552780 A CN201510552780 A CN 201510552780A CN 105126073 B CN105126073 B CN 105126073B
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Abstract
The present invention provides a kind of high stability Nosiheptide solutions and preparation method thereof, belong to technical field of veterinary.The Nosiheptide solution is grouped as by following parts by weight group: 1-5 parts of Nosiheptide, 2-15 parts of cosolvent, 1-3 parts of ethyl alcohol, 0.2-0.5 parts of sodium thiosulfate, 72-93 parts of water, 3-5 parts of stabilizer, the cosolvent is selected from one of dimethylformamide, chloroform, dimethyl sulfoxide and pyridine, and the stabilizer is polyethylene glycol 200 or polyethylene glycol 400.Nosiheptide solution energy of the present invention is mixed with water with arbitrary proportion, is suitable for clinical livestock and fowl drinking water administration, easy to use, bioavilability is high.And increase the stability of Nosiheptide solution by using stabilizer and antioxidant sodium thiosulfate, it avoids its drug in storage and transportation process from being precipitated, influences its using effect.Nosiheptide solution preparation process of the present invention is simple, and equipment is conventional, and raw material is cheap and easy to get, is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of veterinary, and in particular to a kind of solution and preparation method thereof containing Nosiheptide.
Background technique
Nosiheptide belongs to polypeptide antibiotics, legal feed addictive is approved as by Japan in the end of the year 1987, in 1998
Year is approved as three classes novel chiral synthon by China, and the feed medicine that can add for a long time to use in feed was classified as by the Ministry of Agriculture in 2001
Object additive.It since Nosiheptide belongs to macromolecular substances, does not absorb in vivo, therefore do not remain, at present by the European Community, north
The states such as beauty, Japan are widely used.
Nosiheptide be light yellow green brown or yellowish green brown material, be in powdered or fine needle crystal, dimethylformamide,
It is dissolved in chloroform, pyridine and dimethyl sulfoxide, it is insoluble in water in ethyl alcohol, acetone or middle slightly soluble.Nosiheptide is as feed
Additive has the following characteristics that 1. have the apparent effect for promoting growth of animals or poultry and improving efficiency of feed utilization.2. dosage is low
(2.5mg/kg~20mg/kg), use scope are wide (livestock and poultry and aquatic products).3. animal specific antibiotic.4. only bacteriostasis and
Without bactericidal effect.5. pair gram-positive bacteria is effective.6. not generating by R?Drug resistance caused by plasmid, with other antibiotic without
Cross resistance.7. not absorbed by alimentary canal, noresidue problem.8. without any side effects to animal and people using safe.9.
Effect on environment is small, belongs to environment-friendly feed additive.
Existing Nosiheptide is pre-mixing agent and granule respectively there are two types of dosage form, be all with the solid form of Nosiheptide to
Medicine, administration route are single, it has not been convenient to.Therefore, the novel form demand for developing Nosiheptide is more urgent.
Solution means that drug is dissolved in solvent clear liquid preparation generated, and the solute of solution is usually not
Volatile drug, solvent are usually water.Solution can be by drinking water administration, and easy to use, convenient for livestock and poultry absorption, biology is sharp
Expenditure is high.But since Nosiheptide is not soluble in water, it is more difficult to prepare the pharmaceutical solutions of high stability, therefore there are no that currently on the market
The related solution agent of western peptide.
Summary of the invention
It is an object of the invention to overcome the shortcomings of the existing dosage form of Nosiheptide, a kind of suitable drinking water administration, user are provided
Just and the high Nosiheptide solution of stability.
The technical solution adopted for solving the technical problem of the present invention are as follows:
A kind of high stability Nosiheptide solution is grouped as by following parts by weight group: 1-5 parts of Nosiheptide, cosolvent 2-
15 parts, 1-3 parts of ethyl alcohol, 0.2-0.5 parts of sodium thiosulfate, 72-93 parts of water, 3-5 parts of stabilizer.
Preferably, the cosolvent in dimethylformamide, chloroform, dimethyl sulfoxide and pyridine one
Kind.
It is further preferred that the cosolvent is dimethylformamide.
Preferably, the stabilizer is polyethylene glycol 200 or polyethylene glycol 400.
Preferably, the solution is grouped as by following parts by weight group: 2 parts of Nosiheptide, 6 parts of cosolvent, ethyl alcohol 2
Part, 0.3 part of sodium thiosulfate, 86 parts of water, 4 parts of stabilizer.
Invention also provides the preparation methods of Nosiheptide solution, include the following steps:
(1) cosolvent and ethyl alcohol are warming up to 30-50 DEG C, Nosiheptide is added while stirring until it is completely dissolved；
(2) water of 60-80% formula ratio is taken to dissolve sodium thiosulfate and stabilizer；
(3) step (1) and (2) acquired solution are uniformly mixed, and remaining formula ratio water is added, be uniformly mixed up to required
Nosiheptide solution.
Nosiheptide is insoluble in water, cannot directly be mixed with solution with water.Dimethylformamide, chloroform, pyrrole
Pyridine and dimethyl sulfoxide can dissolve Nosiheptide, therefore be selected as cosolvent.Ethyl alcohol also plays the role of hydrotropy, and ethyl alcohol to Nosiheptide
Nosiheptide degradation can be effectively prevented, improve system stability.First Nosiheptide is dissolved in a small amount of cosolvent and ethyl alcohol, is added
Water forms solution.Since the intersolubility of part of auxiliary and water is bad, the compounding agent solution of Nosiheptide directly mixes to be formed with water
Solution stability it is not good enough, storage and transportational process in, solution easily becomes cloudy, so as to cause Nosiheptide precipitation, influence
The assimilation effect of Nosiheptide solution.It is liquid under stabilizer polyethylene glycol 200 or polyethylene glycol 400 room temperature, it is soluble easily in water, it can
To reduce the interfacial tension of cosolvent and water, increase system stability.Polyethylene glycol is sent out during producing storage in order to prevent
Raw oxidation, increases its chemical stability, appropriate antioxidant thiosulfuric acid is also added into Nosiheptide solution of the present invention
Sodium.
The invention has the benefit that
1, Nosiheptide solution energy of the present invention is mixed with water with arbitrary proportion, be suitable for clinical livestock and fowl drinking water to
Medicine, easy to use, bioavilability is high.
2, the stability for increasing Nosiheptide solution by using stabilizer avoids its drug in storage and transportation process from analysing
Out, its using effect is influenced.
3, pass through the effect of antioxidant sodium thiosulfate, during avoiding the production storage of Nosiheptide solution, poly- second
Oxygenolysis occurs for glycol, increases product stability.
4, Nosiheptide solution preparation process of the present invention is simple, and equipment is conventional, and raw material is cheap and easy to get, is suitable for industry
Metaplasia produces.
Specific embodiment
It is explained further the present invention with reference to embodiments, but embodiment does not do any type of limit to the present invention
It is fixed.
Embodiment 1
(1) 6g dimethylformamide and 2g ethyl alcohol are warming up to 30 DEG C, 2g Nosiheptide is added while stirring until it is complete
Dissolution；
(2) 51.6g water dissolution 0.3g sodium thiosulfate and 4g polyethylene glycol 200 are taken；
(3) step (1) and (2) acquired solution are uniformly mixed, and 34.4g water is added, be uniformly mixed up to that required west
Peptide solution agent.
Embodiment 2-4
Nosiheptide solution is prepared using operating method same as Example 1, unlike cosolvent type and each
The proportion of component, the Nosiheptide solution agent prescription are as shown in the table:
Table 1:
5 Nosiheptide solution stability test of embodiment
1, accelerated test
Sample: embodiment 1-3 Nosiheptide solution
Packaging: simulation listing packaging
This product is taken, simulation listing packaging is placed in the drier for filling saturated sodium chloride solution (RH75% ± 5%), then
Being placed in temperature is in 40 DEG C ± 2 DEG C of insulating box, respectively at 1,2,3, sampling in June, investigate the appearance luster of sample, content,
Clarity, related substance, particulate matter, sterile and bacterial endotoxin, obtained experimental result are shown in Table 2.Table 2:
Accelerated test the result shows that, Nosiheptide solution accelerated test 6 months, indices were without significant change, specification 8-
15% Nosiheptide solution is packaged as simulation listing packaging, can be 40 ± 2 DEG C in temperature, the item that relative humidity is 75% ± 5%
Part, which is stablized, to be placed 6 months.
2, long term test
Sample: embodiment 1-3 Nosiheptide solution
Packaging: simulation listing packaging
It in temperature is 25 ± 2 DEG C by test sample, relative humidity is placed 12 months under conditions of being 60% ± 5%, in 3,
6,9,12 months when it is separately sampled, according to pertinent regulations measurement character, content and pH value under " quality standard " item, record result
(result see the table below 3), and compared with same sample 0 month record.
Table 3:
Long-term test results show 8-15% Nosiheptide solution, are packaged as simulation listing packaging, are 25 ± 2 in temperature
DEG C, relative humidity is placed 36 months under conditions of being 60% ± 5%, is stablized, indices are without significant change.
The preferred embodiments of the invention are only listed above, and protection scope of the present invention is not restricted to this, this field
Made any change is each fallen in the scope of the present invention technical staff within the scope of the invention as claimed.
Claims (3)
1. a kind of high stability Nosiheptide solution, which is characterized in that the solution is grouped as by following parts by weight group: that
Western peptide 1-5 parts, 2-15 parts of cosolvent, 1-3 parts of ethyl alcohol, 0.2-0.5 parts of sodium thiosulfate, 72-93 parts of water, 3-5 parts of stabilizer；
The cosolvent is pyridine；
The stabilizer is polyethylene glycol 200 or polyethylene glycol 400.
2. high stability Nosiheptide solution as described in claim 1, which is characterized in that the solution is by following parts by weight
Array is grouped as: 2 parts of Nosiheptide, 6 parts of cosolvent, 2 parts of ethyl alcohol, 0.3 part of sodium thiosulfate, 86 parts of water, 4 parts of stabilizer.
3. the preparation method of high stability Nosiheptide solution, includes the following steps: described in claim 1
(1) cosolvent and ethyl alcohol are warming up to 30-50 DEG C, Nosiheptide is added while stirring until it is completely dissolved；
(2) water of 60-80% formula ratio is taken to dissolve sodium thiosulfate and stabilizer；
(3) step (1) and (2) acquired solution are uniformly mixed, and remaining formula ratio water is added, be uniformly mixed up to that required west
Peptide solution agent.
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| CN105126073B true CN105126073B (en) | 2019-04-05 |
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| CN110575532A (en) * | 2018-06-08 | 2019-12-17 | 上海莫息生物科技有限公司 | Nosiheptide soluble powder and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899599A (en) * | 2005-07-19 | 2007-01-24 | 复旦大学 | Method for preparing Nosiheptide premixed agent |
| CN101299010A (en) * | 2008-06-06 | 2008-11-05 | 浙江汇能动物药品有限公司 | Method for testing content of nosiheptide preparation |
| CN104719634A (en) * | 2015-02-10 | 2015-06-24 | 河北圣雪大成制药有限责任公司 | Method for preparing nosiheptide pre-mixing agent |
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2015
- 2015-09-02 CN CN201510552780.5A patent/CN105126073B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899599A (en) * | 2005-07-19 | 2007-01-24 | 复旦大学 | Method for preparing Nosiheptide premixed agent |
| CN101299010A (en) * | 2008-06-06 | 2008-11-05 | 浙江汇能动物药品有限公司 | Method for testing content of nosiheptide preparation |
| CN104719634A (en) * | 2015-02-10 | 2015-06-24 | 河北圣雪大成制药有限责任公司 | Method for preparing nosiheptide pre-mixing agent |
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Address after: 314400 spring town 3, Changan Town, Haining, Jiaxing, Zhejiang Applicant after: ZHEJIANG ESIGMA BIOTECHNOLOGY CO., LTD. Address before: 314400 spring town 3, Changan Town, Haining, Jiaxing, Zhejiang Applicant before: Zhejiang Huineng Animal Medicine Co., Ltd. |
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