CN103405400B - Levosulpiride injection and preparation method thereof - Google Patents
Levosulpiride injection and preparation method thereof Download PDFInfo
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- CN103405400B CN103405400B CN201310385440.9A CN201310385440A CN103405400B CN 103405400 B CN103405400 B CN 103405400B CN 201310385440 A CN201310385440 A CN 201310385440A CN 103405400 B CN103405400 B CN 103405400B
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Abstract
The invention discloses a levosulpiride injection and a preparation method thereof. The preparation method is characterized by comprising the following steps: selecting a biodegradable encysting material; smashing levosulpiride powder to nanopowder; and preparing a slow release nanocapsule injection under an ultrasonic condition. The purpose of quick effect, stable effect and long effect is realized, the half-life period is prolonged, the compliance is improved, the product stability is increased, and the promising result is obtained.
Description
Technical field
The present invention relates to chemical drugs preparation field, be specifically related to a kind of levosulpiride injection and preparation method thereof.
Background technology
Levosulpiride is a kind of desirable psychosis, is used for the treatment of psychotic disorder, also for the dizziness and headache of obstinate vomit, peptic ulcer and craniocerebral injury.Levosulpiride is developed to injection abroad, has improved bioavailability, realized quick-actingly, but can not realize long-actingly, exist the medication cycle short, patient compliance is poor, and product stability is bad, and effect duration is short to be waited not enoughly, makes troubles to wide patient's medication.
Summary of the invention
The present invention, for overcoming above-mentioned deficiency, provides a kind of levosulpiride nanocapsule slow-release injection and preparation method thereof, has reached quick-acting, steady effect, long-acting object, extended the half-life, improve compliance, increased product stability, obtained promising result.
Invention embodiment is as follows:
Get 19～21 parts, gelatin, 4～6 parts of polymethyl methacrylates, 9～11 parts of arabic gums, inject 200 parts of waters, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get 50 parts of levosulpiridees, 5 parts, D-tartaric acid, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject 600 parts of waters, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add 5 parts, sodium chloride, 1000 parts of waters for injection, stir 10 minutes, add glacial acetic acid and regulate pH to 5.5～6, add 1 part of active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
Compared to the prior art, substantial feature and significant progress are the present invention program:
1 the present invention selects biodegradable one-tenth capsule material, and levosulpiride is ground into nano powder, makes slow release nanocapsule injection under ultrasound condition, plays quick-acting, steady effect, long-acting.
2 the present invention adopt vacuum freezing spraying encystation, and envelop rate is high, good stability.
In the present invention program, related term if no special instructions, is all explained and is as the criterion with medicine related specifications such as Chinese Pharmacopoeia, State Food and Drug Administration's standards.
" part " described in foregoing invention scheme refers to weight portion.
In foregoing invention scheme, the power selection of ultrasonic reactor and spray chilling machine is determined according to the size of institute's production sample amount, by manufacturer's equipment specification regulation, can realize the present invention.
The raw material that above-mentioned embodiment is mentioned is as follows:
Levosulpiride: No. CAS: 23672-07-3;
Gelatin: No. CAS: 9000-70-8;
Polymethyl methacrylate: No. CAS: 9011-14-7;
Arabic gum: No. CAS: 9000-01-5;
Formaldehyde: No. CAS: 50-00-0;
Glacial acetic acid: No. CAS: 64-19-7;
D-tartaric acid: No. CAS: 147-71-7;
Sodium chloride: No. CAS: 7647-14-5;
Above levosulpiride injection raw material used is without specific (special) requirements, and Jun Kecong pharmaceuticals buys and obtains, as long as meet quality standard, all can be used to implement the present invention.
The key equipment that above-mentioned embodiment is mentioned is as follows:
Vacuum Ultrasound Instrument: frequency 10kHz～50kHz, power 1000～5000W;
(typical production manufacturer: Beijing Hongxianglong Biotechnology Development Co., Ltd)
Spray chilling machine: spray chilling temperature-10 ℃～-30 ℃, vacuum pressure 2～30Pa;
(typical production manufacturer: Shanghai Ya Cheng instrument and equipment company limited, the intercontinental environment-development drying equipment of Changzhou company limited)
High energy nanon ball-mill: 20～500nm, power 1000～5000W;
(typical production manufacturer: Qinhuangdao Tai Ji ring nano-machine company limited);
Above levosulpiride injection equipment used is without specific (special) requirements, and all there is sale in market, as long as meet parameter area, all can be used to implement the present invention.
Four specific embodiment
Specific embodiments of the invention 1
Get gelatin 19g, polymethyl methacrylate 4 g, arabic gum 9 g, inject water 200g, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get levosulpiride 50g, D-tartaric acid 5g, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject water 600g, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add sodium chloride 5g, water for injection 1000g, stir 10 minutes, add glacial acetic acid and regulate pH to 5.5, add 1g active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
Specific embodiments of the invention 2
Get gelatin 21g, polymethyl methacrylate 6g, arabic gum 11g, inject water 200g, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get levosulpiride 50g, D-tartaric acid 5g, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject water 600g, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add sodium chloride 5g, water for injection 1000g, stir 10 minutes, add glacial acetic acid and regulate pH to 6, add 1g active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
The preferred specific embodiment 3 of the present invention
Get gelatin 20kg, polymethyl methacrylate 5kg, arabic gum 10kg, inject water 200kg, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get levosulpiride 50kg, D-tartaric acid 5kg, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject water 600kg, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add sodium chloride 5kg, water for injection 1000kg, stir 10 minutes, add glacial acetic acid and regulate pH to 5.8, add 1kg active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
Above embodiment explanation, adopts extreme condition and the optimal conditions of embodiment of the present invention all can make levosulpiride injection, and the levosulpiride injection making with embodiment 3 is below investigated actual effect of the present invention:
Levosulpiride injection half-life contrast prepared by levosulpiride injection prepared by 1 the present invention program and prior art (preparation method of patent No. CN200610026137.X Levogyration sulpiride injection and its).
Table 1 half-life contrast table
The above results shows, the present invention prepares levosulpiride injection and prepares the half-life phenomenal growth of levosulpiride injection, P < 0.01 than adopting existing patented technology.
Levosulpiride injection medication cycle contrast prepared by levosulpiride injection prepared by 2 the present invention program and prior art (preparation method of patent No. CN200610026137.X Levogyration sulpiride injection and its).
Table 2 medication cycle contrast table
The above results shows, the present invention prepares levosulpiride injection and prepares levosulpiride injection medication cycle significant prolongation (P < 0.01) than adopting existing patented technology, increase curative effect, reduced side effect, improved patient's compliance.
3 the present invention program prepare the contrast of levosulpiride nanocapsule envelop rate.
Table 3 envelop rate contrast table
The above results shows, the present invention prepares levosulpiride nanocapsule envelop rate and significantly improves than adopting prior art and preparing nanocapsule envelop rate.
Levosulpiride injection effect duration contrast prepared by levosulpiride injection prepared by 4 the present invention program and prior art (preparation method of patent No. CN200610026137.X Levogyration sulpiride injection and its).。
Table 4 effect duration contrast table
The above results shows, the present invention prepares levosulpiride injection and prepares levosulpiride injection expiry date significant prolongation than adopting existing patented technology, and stability increases.
Levosulpiride injection safety testing prepared by 5 the present invention program.
Method:
The < < chemicals announced according to State Food and Drug Administration is acute, the appended method of long term toxicity investigative technique guideline > > is tested.
Result:
Levosulpiride injection prepared by the present invention program is not found acute, long term toxicity reaction to test white mouse, acts on safe and reliable.
Claims (3)
1. a levosulpiride injection, is characterized in that getting 19～21 parts, gelatin, 4～6 parts of polymethyl methacrylates, 9～11 parts of arabic gums, injects 200 parts of waters, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get 50 parts of levosulpiridees, 5 parts, D-tartaric acid, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject 600 parts of waters, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add 5 parts, sodium chloride, 1000 parts of waters for injection, stir 10 minutes, add glacial acetic acid and regulate pH to 5.5～6, add 1 part of active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection;
The above " part " all refers to weight portion.
2. the preparation method of levosulpiride injection according to claim 1, it is characterized in that getting 19～21 parts, gelatin, 4～6 parts of polymethyl methacrylates, 9～11 parts of arabic gums, inject 200 parts of waters, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get 50 parts of levosulpiridees, 5 parts, D-tartaric acid, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject 600 parts of waters, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add 5 parts, sodium chloride, 1000 parts of waters for injection, stir 10 minutes, add glacial acetic acid and regulate pH to 5.5～6, add 1 part of active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
3. the preparation method of levosulpiride injection according to claim 1, it is characterized in that getting 20 parts, gelatin, 5 parts of polymethyl methacrylates, 10 parts of arabic gums, inject 200 parts of waters, stir 30 minutes, standing 12 hours, with incipient fusion glass sand hourglass sucking filtration, obtain colloid solution, put in ultrasonic reactor; Get 50 parts of levosulpiridees, 5 parts, D-tartaric acid, mixes 30 minutes, the nanometer mixed powder that is ground into 150～200nm with high energy nanon ball-mill, adds in colloid solution, selects supersonic frequency 33kHz, react 1 hour, add 20% formalin, continue reaction 30 minutes, inject 600 parts of waters, in dislocation spray chilling machine, select spray chilling temperature-20 ℃, pressure 25Pa, spraying, obtains levosulpiride nanocapsule; Add 5 parts, sodium chloride, 1000 parts of waters for injection, stir 10 minutes, add glacial acetic acid and regulate pH to 5.8, add 1 part of active carbon and stir 30 minutes, with the de-charcoal of 0.45 μ m filtering with microporous membrane, filtrate is injected ampoule, sealing, 121 ℃ of circulation steam sterilizations 30 minutes, obtain levosulpiride injection.
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| CN201310385440.9A CN103405400B (en) | 2013-08-30 | 2013-08-30 | Levosulpiride injection and preparation method thereof |
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| CN1698591A (en) * | 2005-06-20 | 2005-11-23 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Ginger phenols extract microcapsule and preparation method thereof |
| CN100560068C (en) * | 2006-04-27 | 2009-11-18 | 上海和臣医药工程有限公司 | The preparation method of Levogyration sulpiride injection and its |
| CN102552215B (en) * | 2012-02-02 | 2014-08-13 | 浙江海正药业股份有限公司 | Microcapsule lyophilized powder and preparation method thereof |
| CN102772375B (en) * | 2012-08-23 | 2013-07-17 | 孙威 | Creatine phosphate sodium for injection and preparation method for creatine phosphate sodium for injection |
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Effective date of registration: 20170922 Address after: 226200 No. 88, Jiangsu Road, fine chemical industrial park, Qidong, Jiangsu Patentee after: QIDONG HUATUO PHARMACEUTICAL CO., LTD. Address before: 710 room 90, No. 150000, Xiangjiang Road, Harbin Development Zone, Heilongjiang, China Patentee before: Sun Wei |
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