CN1896050A - Production of gabapendin - Google Patents
Production of gabapendin Download PDFInfo
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- CN1896050A CN1896050A CN 200610051909 CN200610051909A CN1896050A CN 1896050 A CN1896050 A CN 1896050A CN 200610051909 CN200610051909 CN 200610051909 CN 200610051909 A CN200610051909 A CN 200610051909A CN 1896050 A CN1896050 A CN 1896050A
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- gabapentin
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- pentylidene
- butyrolactam
- acid
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Abstract
Production of gabapentin is carried out by 3,3-pentylidene butyrolactam as initial raw material, hydrolyzing to obtain gabapentin salt, converting it into gabapentin hydrate and elutriating out gabapentin from alcohol solvent, neutralizing while adsorbing and decoluring residual hydrate by active carbon and siliceous earth, controlling pH to 8-8.5 and recovering mother-liquid. It is safe and convenient, has short period, less consumption and higher recovery rate. It can be used for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of gabapentin, this method is with 3, and 3-pentylidene butyrolactam is a starting raw material.
Background technology
Gabapentin, chemical name: 1-(aminomethyl) cyclohexyl acetic acid belongs to antiepileptic drug, and is usually used in treating neurogenic pain and anxiety disease.People such as Satzinger reports first in U.S. Pat 4024175.
The preparation method of existing gabapentin has many bibliographical informations, and its main path is neutralized through ion exchange resin or in solution, precipitated and remove hydrochloric acid by the synthetic Gabapentin hydrochloride of different starting raw materials, makes gabapentin through aftertreatment.
A kind of preparation method of gabapentin is disclosed respectively among U.S. Pat 4024175 and the US4087544, by 1,1-cyclohexanediacetic acid mono-methyl and sodium azide in the triethylamine acetone soln through Curtius reaction with by 1, the sodium hypobromite that 1-cyclohexyl oxalic acid monoamide and bromine and sodium hydroxide form reacts through Hofmann in alkaline aqueous solution, obtain Gabapentin hydrochloride with hcl acidifying again, in the aqueous solution, remove hydrochloric acid through anionite-exchange resin, from ethanol/ether mixed solvent, obtain gabapentin again, but do not have the report of purity and yield through aftertreatment.Disclose among the patent WO0234709 by clorox and replace sodium hypobromite to carry out the Hofmann reaction, synthetic Gabapentin hydrochloride obtains the method for gabapentin through anion exchange process, and yield 80% does not still have the purity report.In patent EP414263, US5091567, US5319135 and WO9914184, reported a kind of important intermediate 3 of preparation Gabapentin hydrochloride respectively, 3-pentylidene butyrolactam, 3,3-pentylidene butyrolactam is through hydrochloric acid hydrolysis, get Gabapentin hydrochloride, spent ion exchange resin obtains gabapentin again.Yield is with intermediate 3, and 3-pentylidene butyrolactam is counted 41%-74%.Solvent and condition to ion-exchange among U.S. Pat 4894476, US4960931, the US6528682 have been done corresponding improvement, and the report of key parameter such as purity and chloride ion content is arranged.
The shortcoming that the preparation method of above-mentioned patent exists is that ion exchange process uses a large amount of water as solvent.Gabapentin solubleness in water is bigger, aftertreatment must be distilled most of water recrystallize, in process of production, the process of distilled water needs strict controlled temperature to be lower than 45 ℃, difficulty is big, energy consumption height, major cause be the still-process gabapentin may cyclization be converted into toxicity high 3,3-pentylidene butyrolactam (LD
50=300mg/kg is much higher than the LD of gabapentin
50＞8000mg/kg) (U.S. Pat 6054482) used ethers and alcohols mixed solvent such as methyl alcohol, ethanol, Virahol, ether, isopropyl ether crystallization simultaneously in the operation, cause solvent to utilize difficulty and safety problem in the process again.So problems such as ion exchange method exists operation wayward, and facility investment is big, and the production cycle is long, and yield is low are difficult to accomplish scale production.
For solving the shortcoming that ion exchange method exists aborning, a kind of method is disclosed in U.S. Pat 6576790, Gabapentin hydrochloride is dissolved in the water, preferred sodium hydroxide is transferred pH=7.14 (being the iso-electric point of gabapentin), remove inorganic salt through high pressure by porous-film, this method requires specific installation.Disclose similar isoelectric point precipitation in the U.S. Pat 6518456, pure and mild ether solvent is used in aftertreatment, operates very numerous and diversely, and yield is on the low side.
Disclosing Gabapentin hydrochloride among the Chinese invention patent ZL 200310108375.1 is dissolved in the water, preferred carbonate or supercarbonate are transferred pH=7.2～7.5, be lower than 50 ℃ of distillation moisture content, repeat repeatedly to dissolve, filter and distill the method for removing inorganic salt through alcoholic solvent.But this method is owing to contain a certain amount of carbonic acid gas in the water, in still-process, easily dash material, be difficult to operation, easy toxigenicity impurity 3 in the still-process repeatedly, 3-pentylidene butyrolactam, therefore, product toxic impurity and chloride ion content are wayward, the report that does not also have key parameter such as toxic impurities and chloride ion content, and complicated operating process are not suitable for suitability for industrialized production.
The prospectus of Chinese invention patent application 200510049346.1 discloses a kind of preparation method of gabapentin, though this method adopts sodium alkoxide or pure sylvite adjust pH to remove from repeatedly dissolves, filtration and distillatory process, has increased production cost.
Summary of the invention
The invention provides that a kind of pharmaceutical grade gabapentin is easy, practical, yield is high, be easy to the preparation method of suitability for industrialized production, solved the complex technical process that exists in the prior art, production cycle is long, equipment requirements and energy consumption height, use alcohols and ethers mixed solvent, finished product toxic impurity 3,3-pentylidene butyrolactam and chloride ion content are difficult to control, yield is low, a series of problems such as cost height.
The preparation method of gabapentin of the present invention is with 3, and 3-pentylidene butyrolactam is a starting raw material, and reactions steps comprises:
(1) 3,3-pentylidene butyrolactam mixes the back reaction that is hydrolyzed that heats up with certain density inorganic acid aqueous solution, react after 1～15 hour, reaction system is cooled to-10～20 ℃ of gabapentin salt crystallizations that reaction is generated and separates out, filter, obtain gabapentin salt and mother liquor.
Reaction formula:
Described mineral acid is hydrochloric acid, Hydrogen bromide, sulfuric acid or phosphoric acid, is preferably hydrochloric acid.In reaction formula, be example with hydrochloric acid.The mineral acid mass percent concentration is 5～30%.
In this step reaction 3,3-pentylidene butyrolactam and mineral acid mol ratio are 1: 2～15, preferred 1: 5～10.
The temperature of described hydrolysis reaction is 50～120 ℃, preferred 80～110 ℃.Preferred-5～10 ℃ of the temperature that the crystallization of described gabapentin salt is separated out.
Described mother liquor can feed intake according to actual production and take out a part of mother liquor (A) and add the hydrolysis reaction that mineral acid to the finite concentration of high density is applied mechanically next batch, the remaining mother liquor of applying mechanically (B) of not participating in is used for reclaiming raw material 3,3-pentylidene butyrolactam by reaction.
(2) gabapentin salt is added in the purified water, in-5～40 ℃ of aqueous solution that add alkali, transfer to pH=3～7, the dissolving clarification adds 3 of decolouring of gac and diatomite and absorption small amount of residual, 3-pentylidene butyrolactam, after filtering out gac and diatomite, filtrate is transferred pH=8～8.5 with the aqueous solution of alkali again, is cooled to-10～10 ℃ the gabapentin hydrate is separated out, filter the back with a small amount of frozen water washing leaching cake, obtain gabapentin hydrate and mother liquor (C).
Reaction formula:
Described alkali is NaOH, KOH, NaHCO
3, Na
2CO
3Or NH
3H
2O. preferred KOH or NaOH, more preferably NaOH.
The weight ratio of described gabapentin salt and purified water is: 1: 0.5～5, preferred 1: 1～3.
The gabapentin hydrate of gained is a white crystal.
(3) the gabapentin hydrate is mixed with pure or alcohol, water mixture, mixed 1～5 hour in 0～50 ℃, the gabapentin hydrate changes into gabapentin, being cooled to-10～30 ℃ again separates out gabapentin, filter back with a small amount of cold alcoholic solvent washing leaching cake, get gabapentin and mother liquor (D), gabapentin is in 40～45 ℃ of dryings.Contain callable alcohol in the mother liquor (D), it is mother liquor (E) that universal methods such as employing rectifying reclaim alcohol back nubbin.
Reaction formula:
Described alcohol is C
1～C
4Alcohol can be methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, isopropylcarbinol or its mixture, particular methanol, ethanol, Virahol, more preferably ethanol.
Gabapentin hydrate and alcoholic solvent weight ratio are 1: 1～10, preferred 1: 1.5～3.The weight ratio of gabapentin hydrate and water is 1: 0.1～1.The gabapentin hydrate changes into preferred 20～40 ℃ of the temperature of gabapentin.
The gabapentin that this step reaction generates is a needle-like crystal, and need not further purify just can reach the pharmaceutical grade standard.
The gabapentin for preparing according to the method for the invention detects according to the method that USP-NF describes, its purity＞99.8%, toxicant 3,3-pentylidene butyrolactam＜0.03% or do not detect (require control＜0.1%), chloride ion content is that 20～80ppm (requires to control＜100ppm), do half a year according to the ICH guide and quicken and 1 year normal phase stability experiment, do not find toxicant 3,3-pentylidene butyrolactam increases, and meets the pharmaceutical grade requirement.
Gabapentin preparation method of the present invention has obvious advantage compared with the prior art:
Mother liquor (A) in the step (1) can be applied mechanically continuously, has improved the separation yield and the usage ratio of equipment of product.
After mother liquor (B) described in step (1)～(3), mother liquor (C) and the merging of mother liquor (E) process, add sodium hydroxide, transfer pH=8～14, temperature rising reflux reaction 1～5 hour is cooled to-10～10 ℃, and filtration gets off-white color 3,3-pentylidene butyrolactam.
Reaction formula:
3, the recovery of 3-pentylidene butyrolactam has also improved total reaction yield greatly, has reduced cost.
Step (2) is converted in the gabapentin hydrate process by gabapentin salt, by regulating the pH value for the first time is 3～7, adds decolouring of a certain proportion of gac and diatomite and absorption, and the product outward appearance is improved, residual toxicant 3,3-pentylidene butyrolactam are removed in absorption simultaneously.Compare with pH=7.1～7.8 (as patent US6518456) of open report crystallisation process pH=8～8.5, and yield obviously improves, and impurity reduces.
In step (2)～(3), the operating process that is changed into gabapentin by gabapentin salt is lower than 45 ℃, has avoided the distillation procedure of easy generation toxic impurities, and product quality is easy to control, and energy consumption is low, and is easy to operate.
Technological process choice of Solvent green, environmental protection and safety.The yield height, with 3,3-pentylidene butyrolactam meter, yield＞91%, raw material recycling technology is simple.
Preparation method of the present invention has bigger improvement to prior art, has solved the complex technical process that exists in the gabapentin preparation in the prior art, and the production cycle is long, problems such as cost height, and be more suitable for suitability for industrialized production.
Embodiment
The hydrochloric acid of mentioning among the embodiment and the concentration of sodium hydroxide solution all are mass percent concentrations
The preparation of embodiment 1 Gabapentin hydrochloride
In 2000 milliliters of reaction flasks, add 167 grams 3,3-pentylidene butyrolactam, concentrated hydrochloric acid and 200 milliliters of purified water of 900 grams 31% stir, temperature rising reflux reaction 5 hours, reaction solution is cooled to-5～5 ℃, filter, obtain the wet product of white crystal Gabapentin hydrochloride, be equivalent to dry product 206.5 grams (crystal water is measured and deduction by the Karl-Fisher method), yield 91.1%, purity 98.5%, 3,3-pentylidene butyrolactam content 0.8%.The mother solution hydrochloric acid concentration of aqueous solution is about 15～18%.Part mother liquor (A) is added 36% concentrated hydrochloric acid and is applied mechanically next batch, and residue mother liquor (B) reclaims 3,3-pentylidene butyrolactam.
The preparation of embodiment 2 Gabapentin hydrochlorides
In 2000 milliliters of reaction flasks, add 167 grams 3,3-pentylidene butyrolactam, hydrochloric mother liquor (A) among the 900 gram embodiment 1 is added 300 grams, 36% concentrated hydrochloric acid.Stir, temperature rising reflux reaction 5 hours, reaction solution is cooled to-5～5 ℃, filter, obtain the wet product of white crystal Gabapentin hydrochloride, be equivalent to dry product 216 grams (crystal water is measured and deduction by the Karl-Fisher method), yield 95.3%, purity 98.6%, impurity 3,3-pentylidene butyrolactam content 0.75%.
The preparation of embodiment 3 gabapentin hydrates
In 2000 milliliters of reaction flasks, add 300 milliliters of purified water, the wet product Gabapentin hydrochloride of embodiment 1 (being equivalent to dry product 206 grams), stir, drip 30% sodium hydroxide, accent pH=4～6, dissolving in 15～25 ℃, add 1.5 gram gacs and 0.5 gram diatomite, stirred 0.5 hour, and filtered, filtrate is transferred pH=8.0～8.5 in 0～10 ℃ with 30% aqueous sodium hydroxide solution, white crystal is separated out, continue to be cooled to 0～5 ℃, filter, a small amount of frozen water washing, get the wet product of gabapentin hydrate, be equivalent to dry product 160 grams, yield 85.2%, purity 99.5%, impurity 3,3-pentylidene butyrolactam content＜0.1%.Mother liquor after the separation (C) is used to reclaim 3,3-pentylidene butyrolactam.
The preparation of embodiment 4 gabapentins
In 1000 milliliters of reaction flasks, add 300 milliliter of 95% ethanol and wet product gabapentin hydrate (being equivalent to dry product 160 grams),, be cooled to-5～5 ℃ in 30～40 ℃ of stirrings 2 hours, suction filtration, in 40～50 ℃ of dryings, obtain white crystal gabapentin 137.6 grams, yield 95.0%, purity 99.9%, impurity 3,3-pentylidene butyrolactam does not detect CL
-Content 50ppm.
Contain callable alcohol in the remaining mother liquor (D), it is mother liquor (E) that universal methods such as employing rectifying reclaim the back nubbin.
Embodiment 53, and 3-pentylidene butyrolactam reclaims
In 2000 milliliters of reaction flasks, add the mother liquor (B) among the embodiment 1, the mother liquor among the embodiment 3 (C), mother liquor among the embodiment 4 (E) adds 30% sodium hydroxide, transfers to pH=10～14, stir, be warming up to 100～105 ℃ of back flow reaction 2 hours, backflow is switched to distillation, steam water 300～400 premium on currency, be cooled to 0～5 ℃, filter a small amount of frozen water washing, vacuum-drying, get white solid 3,3-pentylidene butyrolactam 32.5 grams are to drop into 3,3-pentylidene butyrolactam amount meter, the rate of recovery 19%, 89～91 ℃ of fusing points, purity 99.5% can be directly used in as starting raw material.
Gabapentin is carried out stability test, and the result is as follows:
1. accelerated stability research
Accelerated stability research is carried out according to 40 ± 2 ℃ of temperature of stipulating in the ICH guide and relative humidity 75 ± 5%.
Accelerated stability research is let pass continuously to criticize to three and is studied every batch six sample packet, every bag 10g, packaged by imitative commercially available back is sealed in the double-layer polyethylene plastics bag, be put in the fiber can, store, and time in accordance with regulations and project are tested by following condition.
Test condition: temperature: 40 ± 2 ℃, relative humidity 75 ± 5%
In the time of between inspection interval: 0,1,2,3 and 6 months
Research total time: 6 months, result such as table 1:
Table 1: accelerated stability data
| Lot number | Time (moon) | Proterties | Moisture content | Content | Impurity | ||
| Correlative A (II) LOD 0.04ppm | Other unknown single impurity | Total impurities | |||||
| 20041201 | 0 | √ | 0.03％ | 100.96％ | Do not detect | 0.05％ | 0.05％ |
| 1 | √ | 0.02％ | 100.01％ | Do not detect | 0.06％ | 0.06％ | |
| 2 | √ | 0.02％ | 100.30％ | Do not detect | 0.05％ | 0.05％ | |
| 3 | √ | 0.03％ | 100.41％ | Do not detect | 0.05％ | 0.05％ | |
| 6 | √ | 0.03％ | 99.99％ | Do not detect | 0.06％ | 0.06％ | |
| 20041202 | 0 | √ | 0.02％ | 101.36％ | Do not detect | 0.04％ | 0.04％ |
| 1 | √ | 0.03％ | 100.30％ | Do not detect | 0.04％ | 0.04％ | |
| 2 | √ | 0.02％ | 100.28％ | Do not detect | 0.04％ | 0.04％ | |
| 3 | √ | 0.02％ | 101.19％ | Do not detect | 0.04％ | 0.04％ | |
| 6 | √ | 0.03％ | 100.01％ | Do not detect | 0.05％ | 0.05％ | |
| 20041203 | 0 | √ | 0.02％ | 100.96％ | Do not detect | 0.06％ | 0.06％ |
| 1 | √ | 0.03％ | 100.30％ | Do not detect | 0.06％ | 0.06％ | |
| 2 | √ | 0.03％ | 100.27％ | Do not detect | 0.04％ | 0.04％ | |
| 3 | √ | 0.03％ | 100.43％ | Do not detect | 0.05％ | 0.05％ | |
| 6 | √ | 0.02％ | 99.84％ | Do not detect | 0.06％ | 0.06％ | |
Annotate √: show that outward appearance does not change
Conclusion: assay shows that this product 40 ℃ of imitative commercially available backs of RH75% under acceleration environment are deposited 6 months not significant variations, so can think that the gabapentin for preparing according to the method for the invention is stable under acceleration environment.
2. gabapentin Journal of Sex Research steady in a long-term
Journal of Sex Research steady in a long-term carries out according to 25 ± 2 ℃ of temperature of stipulating in the ICH guide and relative humidity 60 ± 5%.
Journal of Sex Research steady in a long-term is let pass continuously to criticize to three and is studied every batch 12 sample packet, every bag 10g, packaged by imitative commercially available back is sealed in the double-layer polyethylene plastics bag, be put in the fiber can, store, and time in accordance with regulations and project are tested by following condition.
Test condition: temperature: 25 ± 2 ℃ of relative humidity 60 ± 5%
In the time of between inspection interval: 0,3,6,9,12,18,24,36 and 48 months
Research total time: 48 months
Result such as table 2:
Table 2 permanent stability data
| Lot number | Time (moon) | Proterties | Moisture content | Content | Impurity | ||
| Related substances A (II) LOD 0.04ppm | Other unknown single impurity | Total impurities | |||||
| 20041201 | 0 | √ | 0.03％ | 100.96％ | Do not detect | 0.05％ | 0.05％ |
| 3 | √ | 0.03％ | 99.75％ | Do not detect | 0.06％ | 0.06％ | |
| 6 | √ | 0.02％ | 100.33％ | Do not detect | 0.07％ | 0.07％ | |
| 9 | √ | 0.03％ | 100.30％ | Do not detect | 0.06％ | 0.06％ | |
| 12 | √ | 0.03％ | 100.13％ | Do not detect | 0.03％ | 0.03％ | |
| 20041202 | 0 | √ | 0.02％ | 101.36％ | Do not detect | 0.04％ | 0.04％ |
| 3 | √ | 0.03％ | 100.08％ | Do not detect | 0.04％ | 0.04％ | |
| 6 | √ | 0.02％ | 100.64％ | Do not detect | 0.05％ | 0.05％ | |
| 9 | √ | 0.02％ | 100.41％ | Do not detect | 0.04％ | 0.04％ | |
| 12 | √ | 0.03％ | 100.00％ | Do not detect | 0.02％ | 0.02％ | |
| 20041203 | 0 | √ | 0.02％ | 100.96％ | Do not detect | 0.06％ | 0.06％ |
| 3 | √ | 0.03％ | 99.82％ | Do not detect | 0.06％ | 0.06％ | |
| 6 | √ | 0.03％ | 100.25％ | Do not detect | 0.07％ | 0.07％ | |
| 9 | √ | 0.02％ | 100.12％ | Do not detect | 0.07％ | 0.07％ | |
| 12 | √ | 0.02％ | 100.58％ | Do not detect | 0.03％ | 0.03％ | |
Annotate √: show that outward appearance does not change
Conclusion: assay shows, this product 25 ℃ of imitative commercially available backs of RH60% under acceleration environment are deposited 12 months not significant variations, so can think that the gabapentin for preparing according to the method for the invention is stable under long-term condition, test of long duration is still being proceeded.
Claims (10)
1, a kind of preparation method of gabapentin, with 3,3-pentylidene butyrolactam is a starting raw material, comprises following reactions steps:
(1) 3,3-pentylidene butyrolactam and inorganic acid aqueous solution are blended in the reaction that is hydrolyzed under 50～120 ℃ of temperature, obtain gabapentin salt through cooling, filtration, and the part acid filtrate returns hydrolysis reaction and applies mechanically;
(2) gabapentin salt is added in the purified water, under-5～40 ℃ of temperature, the aqueous solution with alkali transfers to pH=3～7, the dissolving clarification, add the decolouring of gac and diatomite also the absorption small amount of residual 3,3-pentylidene butyrolactam, filter out gac and diatomite after, the aqueous solution with alkali transfers to pH=8～8.5 again, is cooled to-10～20 ℃ and makes the gabapentin hydrate separate out and filter;
(3) gabapentin hydrate and alcohol or alcohol, water mixture are lower than 50 ℃ under and mix, react and finish postcooling gabapentin is separated out, the filtration after drying.
2, the preparation method of gabapentin as claimed in claim 1 is characterized in that: the described mineral acid of step (1) is hydrochloric acid, Hydrogen bromide, sulfuric acid or phosphoric acid.
3, the preparation method of gabapentin as claimed in claim 1 is characterized in that: the described mineral acid mass percent concentration of step (1) is 5～30%.
4, the preparation method of gabapentin as claimed in claim 1 is characterized in that: in the step (1) 3,3-pentylidene butyrolactam and mineral acid mol ratio are 1: 2～15.
5, the preparation method of gabapentin as claimed in claim 1 is characterized in that: the described alkali of step (2) is NaOH, KOH, NaHCO
3, Na
2CO
3Or NH
3H
2O.
6, the preparation method of gabapentin as claimed in claim 1 is characterized in that: the weight ratio of described gabapentin salt of step (2) and purified water is 1: 0.5～5.
7, the preparation method of gabapentin as claimed in claim 1 is characterized in that: described gac of step (2) and diatomaceous weight ratio are 1: 0.1～5.
8, the preparation method of gabapentin as claimed in claim 1 is characterized in that: the described alcohol of step (3) is methyl alcohol, ethanol, Virahol, n-propyl alcohol, isopropylcarbinol, propyl carbinol or its mixture.
9, the preparation method of gabapentin as claimed in claim 1 is characterized in that: described gabapentin hydrate of step (3) and pure weight ratio are 1: 1～5.
10, the preparation method of gabapentin as claimed in claim 1, it is characterized in that: the remaining aqueous solution behind filtrate in step (1)～(3) or the recovery alcoholic solvent is merged, with the sodium hydroxide adjust pH is that 8～14 times, temperature are to carry out ring-closure reaction under 60～120 ℃, obtain raw material 3,3-pentylidene butyrolactam through the aftertreatment recovery.
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|---|---|---|---|
| CNB2006100519095A CN100398513C (en) | 2006-06-12 | 2006-06-12 | Production of gabapendin |
| US11/457,023 US7442834B2 (en) | 2006-06-12 | 2006-07-12 | Process suitable for industrial scale production of gabapentin |
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|---|---|---|---|
| CNB2006100519095A CN100398513C (en) | 2006-06-12 | 2006-06-12 | Production of gabapendin |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363598A (en) * | 2011-11-25 | 2012-02-29 | 浙江精进药业有限公司 | Method for preparing high-purity gabapentin |
| CN104402744A (en) * | 2014-11-28 | 2015-03-11 | 太仓运通生物化工有限公司 | Preparation method for gabapentin |
| CN104447372A (en) * | 2014-11-26 | 2015-03-25 | 太仓运通生物化工有限公司 | Preparation method of gabapentin |
| CN104496833A (en) * | 2014-11-26 | 2015-04-08 | 太仓运通生物化工有限公司 | Gabapentin synthesis technology |
| CN105061240A (en) * | 2015-08-18 | 2015-11-18 | 太仓运通生物化工有限公司 | Preparation method for high-purity gabapentin |
| CN105061242A (en) * | 2015-08-18 | 2015-11-18 | 太仓运通生物化工有限公司 | Gabapentin purification method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20012750A1 (en) * | 2001-12-21 | 2003-06-21 | Procos Spa | PROCESS FOR THE PRODUCTION OF 1- (AMINOMETHYL) -CYCLOHEXYL-ACETIC ACID IN PURE FORM |
| CN1245379C (en) * | 2003-10-30 | 2006-03-15 | 曹桂东 | Method for preparing gabapentin |
-
2006
- 2006-06-12 CN CNB2006100519095A patent/CN100398513C/en active Active
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363598A (en) * | 2011-11-25 | 2012-02-29 | 浙江精进药业有限公司 | Method for preparing high-purity gabapentin |
| CN102363598B (en) * | 2011-11-25 | 2014-02-12 | 浙江精进药业有限公司 | Method for preparing high-purity gabapentin |
| CN104447372A (en) * | 2014-11-26 | 2015-03-25 | 太仓运通生物化工有限公司 | Preparation method of gabapentin |
| CN104496833A (en) * | 2014-11-26 | 2015-04-08 | 太仓运通生物化工有限公司 | Gabapentin synthesis technology |
| CN104402744A (en) * | 2014-11-28 | 2015-03-11 | 太仓运通生物化工有限公司 | Preparation method for gabapentin |
| CN105061240A (en) * | 2015-08-18 | 2015-11-18 | 太仓运通生物化工有限公司 | Preparation method for high-purity gabapentin |
| CN105061242A (en) * | 2015-08-18 | 2015-11-18 | 太仓运通生物化工有限公司 | Gabapentin purification method |
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| Publication number | Publication date |
|---|---|
| CN100398513C (en) | 2008-07-02 |
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