CN101467987B - Method for preparing lidocaine carbonate injection - Google Patents
Method for preparing lidocaine carbonate injection Download PDFInfo
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- CN101467987B CN101467987B CN2007101730641A CN200710173064A CN101467987B CN 101467987 B CN101467987 B CN 101467987B CN 2007101730641 A CN2007101730641 A CN 2007101730641A CN 200710173064 A CN200710173064 A CN 200710173064A CN 101467987 B CN101467987 B CN 101467987B
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Abstract
The invention provides a preparation method for lidocaine carbonate injection. The invention adds a vibrating step to original process to overcome shortage of current technology, obviously improve visible foreign matters, and raise quality of product, and bring benefit to the safety and efficiency of medicament. The invention is suitable for industrialized production.
Description
Technical field:
The present invention relates to pharmaceutical preparation.Be specifically related to the method for preparing of lidocaine hydrochloride injection.
Background technology:
Lidocaine hydrochloride injection is clinical acid amide type local anesthetic commonly used; Research has been carried out in the clinical practice of its alkaline solution both at home and abroad in recent years; Lidocaine hydrochloride injection is added sodium bicarbonate injection and is mixed with alkaline solution and makees local anesthetic facing the time spent; Its anesthesia ratio incubation period not alkaline solution has obvious shortening, and analgesic effect obviously prolongs.
Local anaesthetics is to get into neural axoplasm through epilemma and neural axon adventitia, and attached on the sodium channel of epilemma and produce local retardation.Because epilemma and neural axon adventitia are lipid conformations; Medicine must be with fat-soluble higher non-ionic form through this film; Therefore; The anaesthetic effect of local anaesthetics and body fluid pH value have much relations, and the free base that local anaesthetics decomposited in vivo when the body fluid pH value increased increases, and free base was less when the body fluid pH value reduced; The high permeates cell membranes easily of free base lipotropy gets into neurocyte retardance sodium-ion channel, brings into play local anesthetic action rapidly.The lidocaine hydrochloride that belongs to strong acid organic weak base salt mainly exists with ion-type in acid solution; Calculate according to the Henderson-Hasselbalch formula; PKa be 7.86 lignocaine in pH＜6 o'clock non-ionic form lignocaine＜1%, be 11% during pH=7, be 22% during pH=7.3.Improving the solution pH value can make weakly alkaline lignocaine change free nonionic into by the hydrochlorate ion-type; The non-ionic form of lignocaine is increased; Ratio through epilemma and neural axon adventitia increases; Get into the many of neural axoplasm and receptors bind, thus the local anesthesia effect is strengthened, and keep the time limit prolongation.
In clinical research and application foundation to the lidocaine hydrochloride alkaline solution, both at home and abroad manufacturer of drugs has been developed lidocaine carbonate injection again, and these article are that lidocaine hydrochloride and sodium bicarbonate are at CO
2The lidocaine carbonate sterile water solution of processing under the saturation conditions is to produce local anesthesia usefulness by lignocaine with lidocaine hydrochloride injection equally, but because its pH is 6.0～7.5, high than lidocaine hydrochloride injection, at physiological CO
2(pH of lidocaine carbonate is 7.3 to dividing potential drop under 36～45mmHg) conditions, injection back CO
2Overflow, these article are converted into the cell membrane that the lignocaine non-ionic form is infiltrated neurocyte rapidly; And the CO that overflows
2Rapid diffusion can produce following two aspect effects: (1) has direct repression to nerve; (2) CO
2Disperse through the influence of pH being promoted local anaesthetics with catch, neural depression effect is strengthened.
The incubation period of lidocaine carbonate thereby shortening, retardation is strong, rapid-action, of flaccid muscles better.In addition; Because lidocaine hydrochloride local anaesthesia liquid pH value is acid pH 3.5～5.5, can stimulate tissue to cause pain during injection in the medicinal liquid impregnation process, and lidocaine carbonate injection pH value partial neutral (pH6.0～7.5) is in physiological range; Less to tissue stimulation; And local anesthetic action is brought into play in the absorption that its nonionic composition increase can be accelerated lignocaine immediately, thereby alleviates pain when injecting, and is the wider a kind of novel local anesthetis of present clinical practice.Imitated and these article of exploitation can provide a kind of safe and effective local anaesthetics for clinical, satisfy the needs of clinical practice, believe that these article have good market prospect.
Existing preparation method for lidocaine carbonate injection is following:
One, prescription
The material name consumption
Lidocaine hydrochloride 106.6g
Injection sodium bicarbonate 35g
Water for injection adds to 5L
1000
Two, method for preparing
1) dosing: injection sodium bicarbonate, lidocaine hydrochloride are dissolved in 5% (being no more than 10 kilograms at most), 60% water for injection respectively;
2) slowly pour sodium bicarbonate aqueous solution in lidocaine hydrochloride aqueous solution stirring and evenly mixing; Add cold water for injection to full dose; Add needle-use activated carbon and add in the above-mentioned solution, stirring and adsorbing, and in pH value to 6.0～7.5 scopes with the carbon dioxide regulator solution;
3) solution is with titanium filter circulating filtration 15 minutes, and solution was with titanium filter, 0.45 μ m microporous membrane cartridge filter and 0.2 μ m microporous membrane cartridge filter circulating filtration 15 minutes;
4) sampling, article content, pH, visible foreign matters in the middle of measuring, qualified back embedding;
5) sterilization: adopts 100 ℃ of flowing steam sterilization 30min, treat after the leak detection, sterilization end that ampoule temperatures reduces to about 30 ℃.
When above-mentioned lidocaine carbonate injection being carried out complete inspection, find that its visible foreign matters qualification rate is merely 78.5%, reach 97% standard of regulation far away.This be since when sterilization portion C O
2From solution, overflow, cause having crystallization to separate out phenomenon, influenced the qualification rate of visible foreign matters inspection.
Summary of the invention:
Technical problem to be solved by this invention is to overcome the low weak point of above-mentioned visible foreign matters qualification rate, and research design can change the low situation of visible foreign matters qualification rate, is suitable for the lidocaine carbonate injection method for preparing of suitability for industrialized production.
The invention provides a kind of lidocaine carbonate injection method for preparing:
One, prescription
The material name consumption
Lidocaine hydrochloride 106.6g
Injection sodium bicarbonate 35g
Water for injection adds to 5L
1000
Two, preparation
1) dosing: respectively with the injection sodium bicarbonate be dissolved in water for injection 5% (being no more than 10 kilograms at most), lidocaine hydrochloride is dissolved in water for injection 60%;
2) slowly pour sodium bicarbonate aqueous solution in lidocaine hydrochloride aqueous solution stirring and evenly mixing; Add cold water for injection to full dose; Add needle-use activated carbon and add in the above-mentioned solution, stirring and adsorbing, and in pH value to 6.0～7.5 scopes with the carbon dioxide regulator solution;
3) solution is with titanium filter circulating filtration 15 minutes, and solution was with titanium filter, 0.45 μ m microporous membrane cartridge filter and 0.2 μ m microporous membrane cartridge filter circulating filtration 15 minutes;
4) sampling, article content, pH, visible foreign matters in the middle of measuring, qualified back embedding;
5) sterilization: adopts 100 ℃ of flowing steam sterilization 30min, treat after the leak detection, sterilization end that ampoule temperatures reduces to 30 ℃ ± 2 ℃;
6) ampoule of will sterilizing takes out with high capacity industry hydro-extracting cage repeated oscillation and cool off and revert to colourless clear liquid until content under rotating speed 150-250rpm, 1-5 minute condition.
The present invention has following characteristics compared with prior art:
On the basis of former technology, increased the vibration step: the ampoule of after sterilization, will sterilizing takes out repeated oscillation and cooling reverts to colourless clear liquid until content.
Because existing method is after sterilization, portion C O
2Can from solution, overflow, cause having crystallization to separate out phenomenon, influence the qualification rate of visible foreign matters inspection.The present invention is under the situation of the lidocaine carbonate injection after sterilizing about the cabinet 50 that goes out to sterilize is spent; With high capacity industry hydro-extracting cage after handling under rotating speed 150-250rpm, 1-5 minute the condition; Carry out visible foreign matters inspection (check result sees the following form), and cooling reverts to colourless clear liquid until content.Like this, the visible foreign matters of product can be controlled, and production can normally be carried out continuously, and product quality is guaranteed.
The specific embodiment:
Instance 1-10 (instance 10 is former technology contrast):
Prescription:
The material name consumption
Lidocaine hydrochloride 106.6g
Injection sodium bicarbonate 35g
Water for injection adds to 5L
1000
Operating process: (instance 1-9)
1) dosing: injection sodium bicarbonate, lidocaine hydrochloride are dissolved in water for injection respectively;
2) slowly pour sodium bicarbonate aqueous solution in lidocaine hydrochloride aqueous solution stirring and evenly mixing, add cold water for injection to full dose, needle-use activated carbon adds in the above-mentioned solution, stirring and adsorbing, and in pH value to 6.0～7.5 scopes with the carbon dioxide regulator solution;
3) solution is with titanium filter circulating filtration 15 minutes, and solution was with titanium filter, 0.45 μ m microporous membrane cartridge filter and 0.2 μ m microporous membrane cartridge filter circulating filtration 15 minutes;
4) sampling, article content, pH, visible foreign matters in the middle of measuring, qualified back embedding;
5) sterilization: adopts 100 ℃ of flowing steam sterilization 30min, treat after the leak detection, sterilization end that ampoule temperatures reduces to 30 ℃ ± 2 ℃;
6) ampoule of will sterilizing takes out with high capacity industry hydro-extracting cage repeated oscillation and cool off and revert to colourless clear liquid until content under rotating speed 150-250rpm, 1-5 minute condition.
The visible foreign matters assay method of above-mentioned instance product:
Visible foreign matters except as otherwise herein provided; Get 20 of test samples (bottle), remove containers labels, clean container outer wall; Rotation and inverting container suspend (noting not making medicinal liquid to produce bubble) visible foreign matters that exists in the medicinal liquid gently, in case of necessity medicinal liquid are transferred in the clean transparent special glass container; Put test sample in dark slide edge, examination distance (distance of confession under directions test product to human eye is generally 25cm) when bright, under the black and white background, hand-held test sample cervical region overturns medicinal liquid gently, looks with visual inspection respectively.
The inspection of colourless injection or eye drop, illuminance should be 1000～1500lx; The inspection of transparent plastic container or colored solutions injection or eye drop, illuminance should be 2000～3000lx; Suspension type injection and suspension type eye drop, illuminance are 4000lx, only check visible foreign matters such as color lump, cilium.
The result judges
In solution-type intravenous fluid, injection concentrated solution and 20 (bottle) test samples of eye drop, all must not detect visible foreign matters.As the test sample that detects visible foreign matters is no more than 1 (bottle), should get 20 (bottles) in addition with the method inspection, all must not detect.
In 20 (bottle) test samples of suspension type injection and suspension type eye drop, all must not detect visible foreign matters such as color lump, cilium.
The solution-type non-vein is carried out by the pertinent regulations of drug regulatory department under the State Council with injection, injectable sterile powder and injection sterile bulk drug.
The visible foreign matters testing result of product of the present invention:
| ? | Rotating speed (rpm) | Time (minute) | Visible foreign matters qualification rate (%) |
| Instance 1 | 150 | 1 | 82.0 |
| Instance 2 | 150 | 3 | 95.5 |
| Instance 3 | 150 | 5 | 97.6 |
| Instance 4 | 200 | 1 | 87.3 |
| Instance 5 | 200 | 3 | 97.8 |
| Instance 6 | 200 | 5 | 98.2 |
| Instance 7 | 250 | 1 | 90.7 |
| Instance 8 | 250 | 3 | 98.3 |
| Instance 9 | 250 | 5 | 98.5 |
| Instance 10 | Former technology | Former technology | 78.5 |
From above 10 instances, preferred " 200rpm3 minute " this kind condition of the present invention is as the lidocaine carbonate injection optimum condition that vibrates, adopt new method after more former method visible foreign matters qualification rate obviously improve, qualification rate is all greater than 97%.
Claims (1)
1. a preparation method for lidocaine carbonate injection is characterized in that this method comprises the following steps:
One, prescription
The material name consumption
Lidocaine hydrochloride 106.6g
Injection sodium bicarbonate 35g
Water for injection adds to 5L
1000
Two, preparation
1) dosing: respectively with the injection sodium bicarbonate be dissolved in water for injection 5%, lidocaine hydrochloride is dissolved in water for injection 60%;
2) slowly pour sodium bicarbonate aqueous solution in lidocaine hydrochloride aqueous solution stirring and evenly mixing, add cold water for injection to full dose, needle-use activated carbon adds in the above-mentioned solution, stirring and adsorbing, and in pH value to 6.0～7.5 scopes with the carbon dioxide regulator solution;
3) solution is with titanium filter circulating filtration 15 minutes, and solution was with titanium filter, 0.45 μ m microporous membrane cartridge filter and 0.2 μ m microporous membrane cartridge filter circulating filtration 15 minutes;
4) sampling, article content, pH, visible foreign matters in the middle of measuring, qualified back embedding;
5) sterilization: adopts 100 ℃ of flowing steam sterilization 30min, treat after the leak detection, sterilization end that ampoule temperatures reduces to 30 ℃ ± 2 ℃;
6) ampoule of will sterilizing takes out, with high capacity industry hydro-extracting cage repeated oscillation and cool off and revert to colourless clear liquid until content under rotating speed 150-250rpm, 1-5 minute condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101730641A CN101467987B (en) | 2007-12-26 | 2007-12-26 | Method for preparing lidocaine carbonate injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101730641A CN101467987B (en) | 2007-12-26 | 2007-12-26 | Method for preparing lidocaine carbonate injection |
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| Publication Number | Publication Date |
|---|---|
| CN101467987A CN101467987A (en) | 2009-07-01 |
| CN101467987B true CN101467987B (en) | 2012-02-22 |
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| CN2007101730641A Active CN101467987B (en) | 2007-12-26 | 2007-12-26 | Method for preparing lidocaine carbonate injection |
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102078290B (en) * | 2009-11-26 | 2014-01-15 | 华北制药集团制剂有限公司 | Method for preparing carbonate lidocaine injection |
| CN102973494A (en) * | 2011-09-02 | 2013-03-20 | 天圣制药集团股份有限公司 | Preparation method of lidocaine carbonate injection |
| CN103637976B (en) * | 2013-11-14 | 2015-01-21 | 汕头保税区洛斯特制药有限公司 | Aseptic preparation production process |
| CN104173373A (en) * | 2014-08-19 | 2014-12-03 | 上海交通大学医学院附属第九人民医院 | Pharmaceutical composition for treating chronic pain and application of drug composition |
| CN106265923A (en) * | 2015-06-07 | 2017-01-04 | 浙江泰康药业集团有限公司 | A kind of method improving clarity of injection |
| CN106692120A (en) * | 2016-12-15 | 2017-05-24 | 刘力 | Medicine composition of lidocaine and application of medicine composition |
| CN110934854A (en) * | 2020-01-05 | 2020-03-31 | 龚跃明 | Application of lidocaine carbonate in preparation of external medicine for treating premature ejaculation |
| CN115721607B (en) * | 2022-11-19 | 2023-07-21 | 华夏生生药业(北京)有限公司 | Levofloxacin lactate injection and preparation method thereof |
| US20240197621A1 (en) * | 2022-12-19 | 2024-06-20 | Hikma Pharmaceuticals Usa Inc. | Buffered Lidocaine Injectable Formulations and Methods for Making Same |
Citations (1)
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| CN1065203A (en) * | 1992-02-01 | 1992-10-14 | 解放军陆军第44医院 | The compound method that adds the alkali local anaesthetics |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1065203A (en) * | 1992-02-01 | 1992-10-14 | 解放军陆军第44医院 | The compound method that adds the alkali local anaesthetics |
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