CN103720648A - Injection containing mepivacaine hydrochloride and preparation method thereof - Google Patents
Injection containing mepivacaine hydrochloride and preparation method thereof Download PDFInfo
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- CN103720648A CN103720648A CN201310730825.4A CN201310730825A CN103720648A CN 103720648 A CN103720648 A CN 103720648A CN 201310730825 A CN201310730825 A CN 201310730825A CN 103720648 A CN103720648 A CN 103720648A
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Abstract
The invention belongs to the technical field of medicine preparation, and in particular relates to an injection containing mepivacaine hydrochloride and a preparation method thereof. The method comprises the following steps: (1) boiling injection water according to the prescribed amount, cooling to 55-65 DEG C, adding mepivacaine hydrochloride and medical auxiliaries according to the prescribed amount into 20-80 percentage by weight of the injection water, stirring until the materials are completely dissolved to prepare a liquid medicine; (2) adding medical activated carbon into the liquid medicine, stirring and adsorbing at 45-55 DEG C for 10-60 minutes, decarburizing and filtering; (3) adding the rest injection water into the filtrate, regulating the pH value of the liquid medicine to 5.0-6.0 with alkali liquor, and uniformly stirring and mixing; (4) filtering, sampling, inspecting whether the product is qualified or not, filling, sterilizing at 121 DEG C for 10 minutes, and packaging. Compared with the prior art, the injection is simple in preparation process and high in stability, and can be uniformly released in a body to reduce the side effect.
Description
Technical field
The invention belongs to medical preparing technical field, 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, instant effect, and duration of efficacy is long, can effectively 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 reduced to a certain extent consumption.When acting on nervus peripheralis conduction block, Mepivacaine Hydrochloride starts to take effect after 2～4 minutes in injection, and its distributive law is in vivo 0.8, with the combination rate of plasma protein be 60～78%, the pKa value of itself is 7.6.Conventionally the half-life of 600mg Mepivacaine Hydrochloride in blood plasma is 2～3 hours, and for hepatopathy and diabetics, the half-life will extend.Mepivacaine Hydrochloride is mainly completed by liver in the metabolism of human body, and its overwhelming majority is decomposed by bile, and after through intestinal absorption, by urine, get rid of.Toxicological experiment is found: Mepivacaine Hydrochloride is 5～10 μ g/ml to the lethal poison amount of human body, and to compare toxicity little with lignocaine and procaine; There is no animal experiment study data to determine its carcinogenecity, mutagenicity and genotoxicity; Also without showing that about people's data this product may have carcinogenecity, mutagenicity and genotoxicity.
Mepivacaine Hydrochloride is usually used in the local infiltration anesthesia in oral cavity and dental treatment.Mepivacaine hydrochloride inj in France's listing, has been listed prescription handbook in the U.S. at first.The current domestic narcotics market share is mainly occupied by kinds such as procaines.According to statistics, procaine has reached more than 90% in the medication popularity rate of China big city hospital.Research shows that Mepivacaine Hydrochloride reaches the twice of procaine in the curative effect aspect the clinical practices such as infiltration, nerve block and epidural anesthesia, and Mepivacaine Hydrochloride is compared toxicity with procaine with lignocaine less, is 0.81 to 1.0.Abroad clinical practice proves widely, and Mepivacaine Hydrochloride is a local anesthetic having superiority in cost performance, occupies critical role abroad on 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 take mepivacaine optical isomer and epinephrine and pharmaceutical salts thereof as active component, combines with proper auxiliary materials pharmaceutically.But the same with other anesthetis, Mepivacaine Hydrochloride is the in the situation that of 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, chamber property premature contraction, chamber quiver, even heart beating stops waiting series of symptoms.Because Mepivacaine Hydrochloride concentration in vivo is easily gathered at short notice, easily health is caused to certain infringement, 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 aqueous injection of the simple and hydrochloric mepivacaine that can evenly discharge in vivo of a kind of production technology and preparation method thereof.
The aqueous injection of hydrochloric mepivacaine of the present invention, it is comprised of Mepivacaine Hydrochloride and pharmaceutic adjuvant, 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 of 1) getting recipe quantity, after boiling, be cooled to 55 ℃-65 ℃, get the wherein water for injection of 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 ℃-55 ℃, adsorbs decarburization after 10-60 minute and filters; 3) get filtrate, add remaining water for injection, with the pH value of alkali liquor adjusting medicinal liquid, to 5.0-6.0, be uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, and embedding, in 121 ℃ of sterilizing 10min, packing, obtains.
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, 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: respectively organize the blood drug level-time diagram after the product of injected in mice embodiment 1-7.
The specific embodiment
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, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
Embodiment 2
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
Embodiment 4
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
Embodiment 5
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.5 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
Embodiment 7
1, prescription:
2, preparation: 1) get the water for injection of recipe quantity, be cooled to 58 ℃ after boiling, get the water for injection of 40% recipe quantity, add recipe quantity Mepivacaine Hydrochloride and pharmaceutic adjuvant, stir and make it to dissolve completely, make medicinal liquid; 2), to the medicinal carbon that adds 30g in medicinal liquid, stirring and adsorbing in 45 ℃, adsorbs decarburization after 30 minutes and filters; 3) get filtrate, add remaining water for injection, the sodium hydroxide solution that is 0.5mol/L by concentration regulates the pH value to 5.3 of medicinal liquid, is uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, is distributed into 100, embedding, and in 121 ℃ of sterilizing 10min, packing, obtains.
For the stability of preparation prepared by the present invention is described, the preparation of preparing with the embodiment of the present invention 7 is accelerated under 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% condition investigate, 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, in group, all unify to inject the product of same embodiment, and get blood in the 3rd, 6,12,18,24,30,36,42,48,54,60,72 minutes from medication, check its blood drug level.The results are shown in accompanying drawing 1.
Experimental result shows, the relative existing product of Mepivacaine Hydrochloride aqueous injection (being often 3-4 minute) making in this bright described method has all obtained delay release time, can not assemble at short notice, and the product of embodiment 3 and 4 is owing to having controlled 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.Under Montmorillonitum routine, be rarely used in injection, therefore more strictly control its amount and particle diameter at this.
Claims (10)
1. an aqueous injection for hydrochloric mepivacaine, is characterized in that, it is comprised of Mepivacaine Hydrochloride and pharmaceutic adjuvant, and described pharmaceutic adjuvant and the mass ratio of Mepivacaine Hydrochloride are 3:(10-200).
2. the aqueous injection of hydrochloric mepivacaine as claimed in claim 1, is characterized in that, described pharmaceutic adjuvant comprises one or more in sodium chloride, potassium chloride and calcium chloride.
3. the aqueous injection of hydrochloric mepivacaine as claimed in claim 1, is characterized in that, described pharmaceutic adjuvant comprises nanoscale Montmorillonitum, and one or more in sodium chloride, potassium chloride and calcium chloride, and the particle diameter of nanoscale Montmorillonitum is 5-25nm.
4. the aqueous injection of hydrochloric mepivacaine as claimed in claim 3, is characterized in that, the concentration of described Montmorillonitum in aqueous injection is 0.0015-0.0025g/ml.
5. the aqueous injection of hydrochloric mepivacaine as claimed in claim 1, is characterized in that, the concentration of described Mepivacaine Hydrochloride in aqueous injection is 0.01-0.05g/ml.
6. the preparation method of the aqueous injection of the hydrochloric mepivacaine as described in as arbitrary in claim 1-5, it is characterized in that, the concrete steps of described method are: the water for injection of 1) getting recipe quantity, after boiling, be cooled to 55 ℃-65 ℃, get the wherein water for injection of 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 ℃-55 ℃, adsorbs decarburization after 10-60 minute and filters; 3) get filtrate, add remaining water for injection, with the pH value of alkali liquor adjusting medicinal liquid, to 5.0-6.0, be uniformly mixed; 4) filter, sampling, checks, after conforming with the regulations, and embedding, in 121 ℃ of sterilizing 10min, packing, obtains.
7. the preparation method of the aqueous injection of hydrochloric mepivacaine as claimed in claim 6, is characterized in that, described step 2) in, activated carbon dosage is 0.0001-0.05g/ml.
8. the preparation method of the aqueous injection of hydrochloric mepivacaine as claimed in claim 6, is characterized in that, described step 2) in, the activated carbon adsorption time is 5min-30min.
9. the preparation method of the aqueous injection of hydrochloric mepivacaine as claimed in claim 6, is characterized in that, alkali liquor described in step 3) is the solution of medicinal basic preparation, and concentration is 0.01-10mol/L.
10. the preparation method of the aqueous injection of hydrochloric mepivacaine as claimed in claim 6, is characterized in that, alkali liquor described in step 3) is sodium hydroxide solution, and concentration is 0.01-10mol/L.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012233A (en) * | 2015-08-24 | 2015-11-04 | 段鹏静 | Procaine-containing composition for delivery and preparation method |
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| BOBEY18: "盐酸甲哌卡因注射液说明书美国中文翻译", 《百度文库》, 21 May 2013 (2013-05-21) * |
| 山东省经济和信息化委员会: "盐酸甲哌卡因及其注射剂", 《HTTP://WWW.SDEIC.GOV.CN/JZC/BSZN/WEBINFO/2012/11/1350002559366031.HTM》, 15 November 2012 (2012-11-15), pages 1 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012233A (en) * | 2015-08-24 | 2015-11-04 | 段鹏静 | Procaine-containing composition for delivery and preparation method |
| CN105012233B (en) * | 2015-08-24 | 2018-04-20 | 段鹏静 | A kind of composition for being used to give a birth and preparation method containing procaine |
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