CN103720648B - Aqueous injection of a kind of hydrochloric mepivacaine and preparation method thereof - Google Patents
Aqueous injection of a kind of hydrochloric mepivacaine and preparation method thereof Download PDFInfo
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- CN103720648B CN103720648B CN201310730825.4A CN201310730825A CN103720648B CN 103720648 B CN103720648 B CN 103720648B CN 201310730825 A CN201310730825 A CN 201310730825A CN 103720648 B CN103720648 B CN 103720648B
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Abstract
The invention belongs to technical field of medicine preparation, specifically, relate to aqueous injection of a kind of hydrochloric mepivacaine and preparation method thereof.The preparation concrete steps of described aqueous injection are: the water for injection 1) getting recipe quantity, are cooled to 55 DEG C-65 DEG C after boiling, and get the water for injection of wherein 20-80wt%, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add medicinal carbon, stirring and adsorbing in 45 DEG C-55 DEG C, adsorb decarburization after 10-60 minute and filter; 3) get filtrate, add remaining water for injection, regulate the pH value of medicinal liquid to 5.0-6.0 with alkali liquor, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.Compared with prior art, not only technique is simple in the preparation in the present invention, and stability is high, can evenly discharge in vivo, reduces its side effect.
Description
Technical field
The invention belongs to technical field of medicine preparation, specifically, relate to aqueous injection of a kind of hydrochloric mepivacaine and preparation method thereof.
Background technology
Mepivacaine Hydrochloride chemical name N-(2,6-3,5-dimethylphenyl)-1-methyl-2-piperidine formyl amine hydrochlorate is a kind of amino local anesthetic.It acts on sensation and Motor nerve fibre, and instant effect, duration of efficacy is long, effectively can hinder nerve conduction.In anesthetis, add epinephrine can slow down the speed of service of Mepivacaine Hydrochloride in human body, to guarantee anesthesia duration and effect, and reduce consumption to a certain extent.When acting on peripheral nerve block, Mepivacaine Hydrochloride starts to take effect after 2 ~ 4 minutes in injection, and its distributive law is in vivo 0.8, is 60 ~ 78% with the combination rate of plasma protein, and the pKa value of itself is 7.6.The half-life of usual 600mg Mepivacaine Hydrochloride in blood plasma is 2 ~ 3 hours, and for hepatopathy and diabetics, the half-life will extend.Mepivacaine Hydrochloride has come primarily of liver in the metabolism of human body, and its overwhelming majority is decomposed by bile, and after got rid of by urine through intestinal absorption.Toxicological experiment finds: the lethal poison amount of Mepivacaine Hydrochloride to human body is 5 ~ 10 μ g/ml, and to compare toxicity little with lignocaine and procaine; There is no animal experiment study data to determine its carcinogenecity, mutagenicity and genotoxicity; Also show that this product may have carcinogenecity, mutagenicity and genotoxicity without the data about people.
Mepivacaine Hydrochloride is usually used in the local infiltration anesthesia in oral cavity and dental treatment.Mepivacaine hydrochloride inj in France's listing, has listed prescription handbook in the U.S. at first.The current domestic narcotics market share occupies primarily of kinds such as procaines.According to statistics, procaine reaches more than 90% in the medication popularity rate of big city hospital of China.Research shows that the curative effect of Mepivacaine Hydrochloride infiltrating, in the clinical practice such as nerve block and epidural anesthesia reaches the twice of procaine, and Mepivacaine Hydrochloride and lignocaine compare toxicity with procaine less, be 0.81 to 1.0.External clinical practice widely proves, Mepivacaine Hydrochloride is a local anesthetic comparatively had superiority in cost performance, abroad critical role is occupied in local anaesthetics market.Estimate that Mepivacaine Hydrochloride will progressively replace the market share of procaine, become the choice drug of clinical anesthesia, therefore developing this kind will have good market prospect and profit margin.
Chinese patent (CN200910306349.7) just provides a kind of injection preparation containing mepivacaine isomer, and it is with mepivacaine optical isomer and epinephrine and pharmaceutical salts thereof for active component, combines with pharmaceutically proper auxiliary materials.But it is the same with other anesthetis, Mepivacaine Hydrochloride is when excessive use, can cause damage to central nervous system, respiratory system and cardiovascular system, produce eyeball involuntary movement, wild talk, headache, feel sick, dyspnea, bradycardia, hypotension, room property premature contraction, room quiver, even the series of symptoms such as heart beating stopping.Because Mepivacaine Hydrochloride concentration in vivo is easily gathered at short notice, easily cause certain infringement to health, its injection is still in certain defect at present.
Summary of the invention
In order to solve the problems of the technologies described above, the invention provides the simple and aqueous injection of the hydrochloric mepivacaine that can evenly discharge in vivo and preparation method thereof of a kind of production technology.
The aqueous injection of hydrochloric mepivacaine of the present invention, it is made up of Mepivacaine Hydrochloride and pharmaceutic adjuvant, and described pharmaceutic adjuvant and the mass ratio of Mepivacaine Hydrochloride are 3:(10-200).
Described pharmaceutic adjuvant comprises one or more in sodium chloride, potassium chloride and calcium chloride.
Described pharmaceutic adjuvant also comprises nanoscale Montmorillonitum, and its particle diameter is 5-25nm.
The concentration of described Montmorillonitum in aqueous injection is 0.0015-0.0025g/ml.
The concentration of described Mepivacaine Hydrochloride in aqueous injection is 0.01-0.05g/ml.
The preparation method of the aqueous injection of hydrochloric mepivacaine of the present invention, the concrete steps of described method are: the water for injection 1) getting recipe quantity, 55 DEG C-65 DEG C are cooled to after boiling, get the water for injection of wherein 20-80wt%, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stirring makes it to dissolve completely, makes medicinal liquid; 2) in medicinal liquid, add medicinal carbon, stirring and adsorbing in 45 DEG C-55 DEG C, adsorb decarburization after 10-60 minute and filter; 3) get filtrate, add remaining water for injection, regulate the pH value of medicinal liquid to 5.0-6.0 with alkali liquor, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
The preparation method of the aqueous injection of hydrochloric mepivacaine of the present invention, described step 2) in, activated carbon dosage is 0.0001-0.05g/ml.
The preparation method of the aqueous injection of hydrochloric mepivacaine of the present invention, described step 2) in, the activated carbon adsorption time is 5min-30min.
The preparation method of the aqueous injection of hydrochloric mepivacaine of the present invention, in described step 3), described alkali liquor is medicinal accepted all alkali, and concentration is 0.01-10mol/L.
Alkali liquor described in step 3) is sodium hydroxide solution, and concentration is 0.01-10mol/L.
Compared with prior art, the aqueous injection of hydrochloric mepivacaine of the present invention, not only technique is simple in the preparation, and stability is high, can evenly discharge in vivo, reduces its side effect.
Accompanying drawing explanation
Accompanying drawing 1: the blood concentration-time figure after the product of each group injected in mice embodiment 1-7.
Detailed description of the invention
Below in conjunction with specific embodiment, preparation method of the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 2
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 3
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 4
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 5
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 6
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
Embodiment 7
1, prescription:
2, prepare: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, get the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.3 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mol/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
In order to the stability of preparation prepared by the present invention is described, acceleration is carried out under temperature 40 DEG C ± 2 DEG C, relative humidity 75% ± 5% condition to the preparation prepared with the embodiment of the present invention 7 and investigates, the results are shown in following table.
For observing the drug absorption situation of embodiment 1-7, the present invention gets 84 rats of uniform size, be divided into 7 groups each 12, the product injecting same embodiment is all unified in group, and the 3rd, 6,12,18,24,30,36,42,48,54,60,72 minute after medication carries out getting blood, checks its blood drug level.The results are shown in accompanying drawing 1.
Experimental result shows, the Mepivacaine Hydrochloride aqueous injection relative existing product (normal be 3-4 minute) obtained in this bright described method is obtained for delay release time, can not assemble at short notice, and the product of embodiment 3 and 4 is owing to controlling particle diameter and the content of Montmorillonitum, make its release more even, and with prior art even other embodiments of the invention show a sharp contrast.Be rarely used in injection under Montmorillonitum routine, therefore more strictly control its amount and particle diameter at this.
Claims (2)
1. an aqueous injection for hydrochloric mepivacaine, is characterized in that, it is made up of Mepivacaine Hydrochloride, pharmaceutic adjuvant and water for injection; The quality of described Mepivacaine Hydrochloride is 40g; Described pharmaceutic adjuvant is made up of 9.2g sodium chloride, 3.6g nanoscale Montmorillonitum, 0.6g potassium chloride and 0.66g calcium chloride; The mean diameter of described nanoscale Montmorillonitum is 11nm; The concentration of described nanoscale Montmorillonitum in aqueous injection is 0.0018g/ml; The concrete preparation process of described aqueous injection is: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, and gets the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stirs and makes it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mo1/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
2. an aqueous injection for hydrochloric mepivacaine, is characterized in that, it is made up of Mepivacaine Hydrochloride, pharmaceutic adjuvant and water for injection; The quality of described Mepivacaine Hydrochloride is 40g; Described pharmaceutic adjuvant is made up of 9.2g sodium chloride, 3.6g nanoscale Montmorillonitum, 0.6g potassium chloride and 0.66g calcium chloride; The mean diameter of described nanoscale Montmorillonitum is 12nm; The concentration of described nanoscale Montmorillonitum in aqueous injection is 0.0018g/ml; The concrete preparation process of described aqueous injection is: the water for injection 1) getting recipe quantity, is cooled to 58 DEG C after boiling, and gets the water for injection of 40% recipe quantity, adds recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stirs and makes it to dissolve completely, make medicinal liquid; 2) in medicinal liquid, add the medicinal carbon of 30g, stirring and adsorbing in 45 DEG C, adsorb decarburization after 30 minutes and filter; 3) get filtrate, add remaining water for injection, regulate the pH value to 5.5 of medicinal liquid with the sodium hydroxide solution that concentration is 0.5mo1/L, be uniformly mixed; 4) filter, sampling, check, after conforming with the regulations, be distributed into 100, embedding, in 121 DEG C of sterilizing 10min, packaging, to obtain final product.
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| CarbocaineTM;无;《http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012250s033lbl.pdf》;20100225;右栏"DESCRIPTION"部分 * |
| 盐酸甲哌卡因及其注射剂;山东省经济和信息化委员会;《http://www.sdeic.gov.cn/jzc/bszn/webinfo/2012/11/1350002559366031.htm》;20121115;最后1段 * |
| 盐酸甲哌卡因注射液说明书美国中文翻译;bobey18;《百度文库》;20130521;参见[成份]部分 * |
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