CN101948468B - Preparation method of quinine hydrochloride - Google Patents
Preparation method of quinine hydrochloride Download PDFInfo
- Publication number
- CN101948468B CN101948468B CN 201010259713 CN201010259713A CN101948468B CN 101948468 B CN101948468 B CN 101948468B CN 201010259713 CN201010259713 CN 201010259713 CN 201010259713 A CN201010259713 A CN 201010259713A CN 101948468 B CN101948468 B CN 101948468B
- Authority
- CN
- China
- Prior art keywords
- quinine
- preparation
- solution
- hydrochloric acid
- hydrochloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of quinine hydrochloride. The method of the invention comprises the following steps: transforming quinine sulfate to quinine, then dispersing the quinine into a dispersing agent, adding hydrochloric acid or introducing hydrogen chloride gas to react, and the quinine hydrochloride is obtained through the method of crystallization. Only the common acids and bases, and the common solvents with low toxicity and low price are used in the method of the invention, and the chemical reagents with high toxicity are not used. The method has high yield which is same as or close to the theoretical yield, and the yield can reach 110 to 115% measured in terms of the quinine. Further, the method is environmentally friendly. The whole preparation process of theinvention has simple and convenient operation and low cost, and is beneficial to the production amplification.
Description
Technical field
The present invention be more particularly directed to the preparation method of an a kind of quinine hydrochloride and quinine dihydrochloride, belong to separation and purification and derivative preparation field.
Background technology
According to the up-to-date report of the World Health Organization, malaria is the transmissible disease that obvious ascendant trend is arranged except acquired immune deficiency syndrome (AIDS) in the world, and it is a kind of transmissible disease of the torrid zone and subtropical zone, is endangering the healthy of 2,000,000,000 populations; Pernicious malaria causes people more than 400,000,000 to infect and about 3,000,000 people (most children of being) death every year, has become the No.1 killer of harm humans life and health in Africa.
Quinine in the cinchona alkaloid is the human anti-malaria medicaments of finding the earliest and using, and is that separation and purification goes out the quinine monomer early in the twentieth century.Although present antimalarial agent has a lot, the quinine Alkaloid remains the antimalarial agent of modal consumption maximum.
Quinine hydrochloride is mainly used in aspects such as antimalarial, sterilization, is used for the treatment of the subtertian malaria due to the strain of anti-chloroquine worm, also can be used for treating vivax malaria, and its injection is usually used in the patient with severe symptoms; Also be used as the effective ingredient of the pest-resistant medicine of various sterilization, in chemical analysis, be used for the preparation of electrodes selective, in other medicines and health protection product, application is arranged also.
Preparation method's more complicated of existing quinine hydrochloride, this is that directly to obtain quinine very difficult because the total alkali that ledger bark is mentioned carries out separation and purification, and the total alkali direct reaction that hydrochloric acid and ledger bark are mentioned, quinine hydrochloride wherein also is difficult for separation and purification.Therefore, at first be that minimum relatively easy crystallization is separated out according to the vitriol solubleness of quinine in the prior art, earlier obtain total alkaloids by solvent extraction, adding an amount of sulfuric acid again makes quinine alkali in the total alkali form Quinine Sulphate Di HC to be precipitated out the back and to separate with other alkaloid, then Quinine Sulphate Di HC is dissolved in and adds barium chloride solution in the ethanol again, produce the mixing solutions of barium sulfate and quinine hydrochloride by reaction, filter or centrifugal remove barium sulfate after, manage again quinine hydrochloride is crystallized out; Perhaps in the ethanolic soln of quinine, feed hydrogen chloride gas, make the generation quinine hydrochloride.In fact and be not easy these methods seem simply, but, use poisonous bariumchloride, and bariumchloride must be excessive, and the barium sulfate precipitate of formation is near colloid, precipitation and filter more loaded down with trivial details; After in ethanol or methyl alcohol, generating quinine hydrochloride because the intrinsic physicochemical property of quinine hydrochloride, only by condensing crystal or add water, organic solvent filtering for crystallizing etc., often be difficult to obtain qualified quinine hydrochloride crystallization.
Summary of the invention
The shortcoming that the objective of the invention is to overcome prior art provides a kind of preparation method of quinine hydrochloride with not enough.This method has only just simply obtained qualified a quinine hydrochloride and quinine dihydrochloride with alcohol, hydrochloric acid and other common organic solvents.
Purpose of the present invention is achieved through the following technical solutions: a kind of preparation method of quinine hydrochloride, comprise following steps: after Quinine Sulphate Di HC is converted into quinine, quinine is dispersed in the dispersion agent, adds hydrochloric acid again or feed the hydrogen chloride gas precursor reactant, the method by crystallization obtains quinine hydrochloride then;
Described Quinine Sulphate Di HC is converted into quinine and preferably realizes by the following method: with Quinine Sulphate Di HC and water 1: 30～50 mixings of press mass ratio, then the pH value of regulating aforementioned solution with hydrochloric acid is 4～5, and Quinine Sulphate Di HC is dissolved; Be heated to 60～70 ℃ then, under stirring condition, be to stir 1h at least after 9～10 with the sodium hydroxide solution adjust pH, stirring finishes, cooling is filtered and is obtained throw out, is 7～7.5 with clear water washing precipitate to the pH value of water solution that washes out, to precipitate the filter solid carbon dioxide after in 60～70 ℃ of drying 3～4h, obtain quinine;
Described dispersion agent is for dissolving organic solvent or the water of quinine and can dissolving the solvent of the organic solvent formation of quinine;
Described organic solvent is preferably at least a in ethanol, methyl alcohol or the 1-propyl alcohol;
The consumption of described dispersion agent is preferably it, and to use volume be 4～10 times of quinine quality;
It is 36% concentrated hydrochloric acid that described hydrochloric acid preferably uses commercially available mass percent concentration;
The condition optimization of described reaction is in-10～40 ℃ of stirring reactions;
The method of described crystallization is preferably method that volatile matter powder obtains crystallization, reduce temperature obtains the method for crystallization or adds the insoluble solvent obtaining at least a in the method for crystallization;
Described insoluble solvent is the solvent less to the quinine hydrochloride solvability;
Described insoluble solvent is preferably ethyl acetate or acetone;
The preparation method of described quinine hydrochloride more preferably comprises following steps:
(1) Quinine Sulphate Di HC is converted into quinine after, in the quinine that obtains, add the alcohol dissolving be equivalent to 4～10 times of quinine quality, obtain the alcoholic solution of quinine; If the color of quinine solution can add the activated carbon decolorizing that is equivalent to quinine quality 2% more deeply, remove by filter gac;
(2) adding is stirred with hydrochloric acid or the hydrogenchloride of the identical molar mass of quinine in the alcoholic solution of quinine, end when being concentrated into solids and separating out, adding the insoluble solvent that is equivalent to 6～10 times of quinine quality then dissolves under the reflux condition, incline rapidly to, place crystallization, obtain a quinine hydrochloride behind the filtration drying;
(3) adding the hydrochloric acid or the hydrogenchloride that are equivalent to quinine mole number twice in the alcoholic solution of quinine stirs, adding the insoluble solvent that is equivalent to 6～10 times of quinine quality when being concentrated into solids and separating out dissolves under the reflux condition, incline rapidly to, place crystallization, obtain quinine dihydrochloride behind the filtration drying;
Described alcohol is preferably at least a in ethanol, methyl alcohol or the 1-propyl alcohol;
Described insoluble solvent is preferably ethyl acetate or acetone;
The temperature of described reflux is preferably 65～75 ℃;
The crystallization of described quinine hydrochloride obtains the remaining mother liquor in back can reclaim (back dewaters) cover for the production of next batch product.
The present invention has following advantage and beneficial effect with respect to prior art:
(1) the present invention has realized the transformation from Quinine Sulphate Di HC to a quinine hydrochloride and quinine dihydrochloride easily by the better simply processing to Quinine Sulphate Di HC;
(2) the present invention only uses common soda acid and little, the low-cost common solvent of toxicity, does not use the big chemical reagent of toxicity, and the yield height can reach or near theoretical yield (110～115% with quinine alkali calculate), and is environmentally friendly;
(3) whole preparation process of the present invention is simple to operation, and cost is low, is beneficial to amplify to produce.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, but embodiments of the present invention are not limited thereto.
Embodiment 1
(1) preparation of quinine: Quinine Sulphate Di HC and water are pressed 1: 40 mixing of mass ratio, and then the pH value of regulating aforementioned solution with the dilute hydrochloric acid of 1mol/L is 4, and Quinine Sulphate Di HC is dissolved; Be heated to 60 ℃ then, under stirring condition, be that to transfer the pH value of solution be to stir 1h at least after 10 for 5% sodium hydroxide solution with mass percent, stirring finishes, cooling filters out the throw out quinine, and washing throw out with water is 7 to washing out pH value of aqueous solution, quinine behind the filter solid carbon dioxide obtains quinine in 60 ℃ of dry 4h.
The preparation of (2) one quinine hydrochlorides: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 22mL methyl alcohol stirring at room, slowly drip mass percent concentration and be 36% the about 0.91mL of concentrated hydrochloric acid, stirring reaction 20min under the airtight situation.Concentrating under reduced pressure solids in the bottle ends when separating out fully, adds the 32ml ethyl acetate in bottle, after 65～70 ℃ of reflux dissolvings, be positioned over 4～8 ℃ of freezing and crystallizings, to be crystallized fully after, suction filtration rapidly, dry in 60～70 ℃ of baking ovens, obtain 3.90 grams, one quinine hydrochloride (molecular formula C
20H
24N
2O
2, HCl2H
2O), yield is 120%.One quinine hydrochloride of gained is the flash of light needle-like crystal of white, mercerising shape, and weathering takes place in warm air, and odorless has strong bitter taste, and 1g dissolves in the water of 16mL, or 1mL ethanol, or the glycerine of about 7mL, or the chloroform of about 1mL, and the utmost point is insoluble in ether; 1 gram, one quinine hydrochloride is dissolved in the 20mL water of removing carbonic acid gas, and the pH of solution is 6.0～6.8; Specific rotation
(200mg is dissolved in 0.1M hydrochloric acid 10mL).
(3) preparation of quinine dihydrochloride: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 22mL methyl alcohol stirring at room, slowly drip mass percent concentration and be 36% the about 1.8mL of concentrated hydrochloric acid, stirring reaction 20min under the airtight situation.Be evaporated to when solids is all separated out in the bottle and stop to concentrate, add the 30ml ethyl acetate, after 65～75 ℃ of reflux make dissolving fully, place 4～8 ℃ of freezing and crystallizings, to be crystallized fully after, suction filtration rapidly, dry in 60～70 ℃ of baking ovens, obtain 3.92 gram quinine dihydrochloride (molecular formula C
20H
24N
2O
22HCl), yield 121%, the gained quinine dihydrochloride is the white solid powder, and is very easily water-soluble, is dissolved in ethanol; The pH value of 3% (w/v) solution is 2.0～3.0; Specific rotation
The 0.1M hydrochloric acid soln).
Embodiment 2
(1) preparation of quinine: Quinine Sulphate Di HC and water are pressed 1: 45 mixing of mass ratio, and then the pH value of regulating aforementioned solution with the dilute hydrochloric acid of 1mol/L is 4, and Quinine Sulphate Di HC is dissolved; Be heated to 60 ℃ then, under stirring condition, be that to transfer the pH value of solution be to stir 1h at least after 10 for 5% sodium hydroxide solution with mass percent, stirring finishes, cooling filters out the throw out quinine, and washing throw out to pH value with water is 8, the throw out quinine is filtered the back in 65 ℃ of dry 4h, obtains quinine.
The preparation of (2) one quinine hydrochlorides: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 18mL ethanol alcohol stirring at room, slowly drip mass percent concentration and be 36% the about 0.91mL of concentrated hydrochloric acid, stirring reaction 25min under the airtight situation.End when concentrating under reduced pressure just solids occurred in the bottle, in bottle, add 25ml acetone, after 70～75 ℃ of heating for dissolving, be positioned over crystallizing at room temperature, to be crystallized fully after, suction filtration, dry in 70 ℃ of baking ovens, obtain 3.83 grams, one quinine hydrochloride (molecular formula C
20H
24N
2O
2, HCl2H
2O), yield 118%.One quinine hydrochloride of gained is the flash of light needle-like crystal of white, mercerising shape, and weathering takes place in warm air, and odorless has strong bitter taste, and 1g dissolves in the water of 16mL, or 1mL ethanol, or the glycerine of about 7mL, or the chloroform of about 1mL, and the utmost point is insoluble in ether; 1 gram, one quinine hydrochloride is dissolved in the 20mL water of removing carbonic acid gas, and the pH of solution is 6.0～6.8; Specific rotation
(200mg is dissolved in 0.1M hydrochloric acid 10mL).
(3) preparation of quinine dihydrochloride: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 18mL ethanol stirring at room, slowly drip mass percent concentration and be 36% the about 1.8mL of concentrated hydrochloric acid, stirring reaction 30min under the airtight situation.Be evaporated to when solids is all separated out in the bottle and stop to concentrate, add 28ml acetone, in 65～70 degree reflux to dissolving fully, room temperature is placed crystallization, to be crystallized fully after, suction filtration, dry in 60～70 ℃ of baking ovens, obtain 3.90 gram quinine dihydrochloride (molecular formula C
20H
24N
2O
2.2HCl), yield 120%.The quinine dihydrochloride of gained is the white solid powder, and is very easily water-soluble, is dissolved in ethanol; The pH value of 3% (w/v) solution is 2.0～3.0; Specific rotation
(the 0.1M hydrochloric acid soln of 3% (w/v)).
Embodiment 3
(1) preparation of quinine: Quinine Sulphate Di HC and water are pressed 1: 50 mixing of mass ratio, and then the pH value of regulating aforementioned solution with the dilute hydrochloric acid of 1mol/L is 4, and Quinine Sulphate Di HC is dissolved; Be heated to 60 ℃ then, under stirring condition, be that to transfer the pH value of solution be to stir 1h at least after 10 for 5% sodium hydroxide solution with mass percent, stirring finishes, cooling filters out the throw out quinine, and washing throw out to the pH value of water solution that leaches with water is 7.5, in 70 ℃ of dry 3h, obtain quinine after the throw out quinine that filters out.
The preparation of (2) one quinine hydrochlorides: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 24mL1-propyl alcohol stirring at room, slowly drip mass percent concentration and be 36% the about 0.9mL of concentrated hydrochloric acid, stirring reaction 30min under the airtight situation.When concentrating under reduced pressure recovery solvent to solids is separated out fully on Rotary Evaporators, add 30ml acetone, dissolve fully in 70～75 ℃ of reflux to precipitates, pour out while hot in the beaker, crystallization is separated out, to be crystallized fully after, rapid suction filtration, dry in 60～70 ℃ of baking ovens, obtain 3.93 grams, one quinine hydrochloride, yield 121%.One quinine hydrochloride of gained is the flash of light needle-like crystal of white, mercerising shape, and weathering takes place in warm air.Odorless has strong bitter taste, and 1g dissolves in the water of 16mL, or 1mL ethanol, or the glycerine of about 7mL, or the chloroform of about 1mL, and the utmost point is insoluble in ether; 1 gram, one quinine hydrochloride is dissolved in the 20mL water of removing carbonic acid gas, and the pH of solution is 6.0～6.8; Specific rotation
(200mg is dissolved in 0.1M hydrochloric acid 10mL).
(3) preparation of quinine dihydrochloride: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 24mL1-propyl alcohol stirring at room, slowly drip mass percent concentration and be 36% the about 1.8mL of concentrated hydrochloric acid, stirring reaction 30min under the airtight situation.End when solvent evaporated under reduced pressure to solids is separated out fully, add the 30ml ethyl acetate and dissolve in 70～75 ℃ of reflux, place 4～8 ℃ of freezing and crystallizings, to be crystallized fully after, suction filtration is dry in 60～70 ℃ of baking ovens rapidly, obtains 3.95 gram quinine dihydrochloride (molecular formula C
20H
24N
2O
22HCl), yield 122%.The quinine dihydrochloride of gained is the white solid powder, and is very easily water-soluble, is dissolved in ethanol; The pH value of 3% (w/v) solution is 2.0～3.0; Specific rotation
(the 0.1M hydrochloric acid soln of 3% (w/v)).
Embodiment 4
(1) preparation of quinine: Quinine Sulphate Di HC and water are pressed 1: 50 mixing of mass ratio, and then the pH value of regulating aforementioned solution with the dilute hydrochloric acid of 1mol/L is 4, and Quinine Sulphate Di HC is dissolved; Be heated to 60 ℃ then, under stirring condition, be that to transfer the pH value of solution be to stir 1h at least after 10 for 5% sodium hydroxide solution with mass percent, stirring finishes, cooling filters out the throw out quinine, and washing throw out to pH value with water is 7, the throw out that filters out obtains quinine in 60 ℃ of dry 4h.
The preparation of (2) one quinine hydrochlorides: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add the dissolving of 20mL ethanol stirring at room, slowly drip mass percent concentration and be 36% the about 0.90mL of concentrated hydrochloric acid, stirring reaction 30min under the airtight situation.Concentrating under reduced pressure solids in the bottle ends when separating out fully, adds the 35ml ethyl acetate in bottle, after 70～75 ℃ of reflux dissolvings, room temperature is placed crystallization, to be crystallized fully after, suction filtration, dry in 60～70 ℃ of baking ovens, obtain 3.90 grams, one quinine hydrochloride (molecular formula C
20H
24N
2O
2, HCl2H
2O), yield 120%.One quinine hydrochloride of gained is the flash of light needle-like crystal of white, mercerising shape, and weathering takes place in warm air.Odorless has strong bitter taste, and 1g dissolves in the water of 16mL, or 1mL ethanol, or the glycerine of about 7mL, or the chloroform of about 1mL, and the utmost point is insoluble in ether; 1 gram, one quinine hydrochloride is dissolved in the 20mL water of removing carbonic acid gas, and the pH of solution is 6.0～6.8; Specific rotation
(200mg is dissolved in 0.1M hydrochloric acid 10mL).
(3) preparation of quinine dihydrochloride: take by weighing the 3.24g quinine in the 100mL round-bottomed flask, add 20mL ethanol and dissolve in stirring at room, slowly drip mass percent concentration and be 36% the about 1.8mL of concentrated hydrochloric acid, stirring reaction 25min under the airtight situation.End when solvent evaporated under reduced pressure to solids is all separated out, add behind the acetone 35ml in 70～75 ℃ of reflux dissolvings, place crystallization, to be crystallized fully after, suction filtration rapidly, dry 3h in 65～70 ℃ of baking ovens obtains 3.93 gram quinine dihydrochloride (molecular formula C
20H
24N
2O
22HCl), yield 121%.The quinine dihydrochloride of gained is the white solid powder, and is very easily water-soluble, is dissolved in ethanol; The pH value of 3% (w/v) solution is 2.0～3.0; Specific rotation
(the 0.1M hydrochloric acid soln of 3% (w/v)).
Above-described embodiment is preferred implementation of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (4)
1. the preparation method of a quinine hydrochloride is characterized in that comprising following steps:
(1) Quinine Sulphate Di HC is converted into quinine after, in the quinine that obtains, add the alcohol dissolving be equivalent to 4～10 times of quinine quality, obtain the alcoholic solution of quinine;
(2) add hydrochloric acid or hydrogenchloride stirring with the identical molar mass of quinine in the alcoholic solution of quinine, end when being concentrated into solids and separating out, adding the insoluble solvent that is equivalent to 6～10 times of quinine quality then dissolves under the reflux condition, incline rapidly to, place crystallization, obtain a quinine hydrochloride behind the filtration drying;
(3) adding the hydrochloric acid or the hydrogenchloride that are equivalent to quinine mole number twice in the alcoholic solution of quinine stirs, adding the insoluble solvent that is equivalent to 6～10 times of quinine quality when being concentrated into solids and separating out dissolves under the reflux condition, incline rapidly to, place crystallization, obtain quinine dihydrochloride behind the filtration drying;
Described insoluble solvent is ethyl acetate or acetone.
2. preparation method according to claim 1, it is characterized in that: described Quinine Sulphate Di HC is converted into quinine and realizes by the following method: Quinine Sulphate Di HC and water are pressed mass ratio 1:30～50 mixings, then the pH value of regulating aforementioned solution with hydrochloric acid is 4～5, and Quinine Sulphate Di HC is dissolved; Be heated to 60～70 ℃ then, under stirring condition, be to stir 1h at least after 9～10 with the sodium hydroxide solution adjust pH, stirring finishes, cooling is filtered and is obtained throw out, is 7～7.5 with clear water washing precipitate to the pH value of water solution that washes out, to precipitate the filter solid carbon dioxide after in 60～70 ℃ of drying 3～4h, obtain quinine.
3. preparation method according to claim 1, it is characterized in that: the color of quinuclidinol solution can add the activated carbon decolorizing that is equivalent to quinine quality 2% more deeply described in the step (1), removes by filter gac.
4. preparation method according to claim 1 is characterized in that: described alcohol is at least a in ethanol, methyl alcohol or the 1-propyl alcohol;
The temperature of described reflux is 70～75 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010259713 CN101948468B (en) | 2010-08-20 | 2010-08-20 | Preparation method of quinine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010259713 CN101948468B (en) | 2010-08-20 | 2010-08-20 | Preparation method of quinine hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101948468A CN101948468A (en) | 2011-01-19 |
| CN101948468B true CN101948468B (en) | 2013-09-04 |
Family
ID=43452110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010259713 Expired - Fee Related CN101948468B (en) | 2010-08-20 | 2010-08-20 | Preparation method of quinine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101948468B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106336410B (en) * | 2016-08-29 | 2017-12-08 | 江苏嘉逸医药有限公司 | A kind of preparation technology of quinidine sulfate dihydrate highly finished product |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402634A (en) * | 2008-11-11 | 2009-04-08 | 广州普星药业有限公司 | Separation and purification process for alkaloid in cinchona bark |
-
2010
- 2010-08-20 CN CN 201010259713 patent/CN101948468B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402634A (en) * | 2008-11-11 | 2009-04-08 | 广州普星药业有限公司 | Separation and purification process for alkaloid in cinchona bark |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101948468A (en) | 2011-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1751056A (en) | Ferric organic compounds, uses thereof and methods of making same | |
| JP4892915B2 (en) | Epalrestat manufacturing method | |
| RU2613555C2 (en) | Monohydrate crystal of fimasartan potassium salt, method for preparing same, and pharmacological composition comprising same | |
| CN111548310B (en) | Levosimendan sodium crystal form and preparation method thereof | |
| CN105801636A (en) | Synthetic method for naringin dihydrochalcone | |
| CN102250025B (en) | Preparation method suitable for industrially producing oteracil potassium | |
| CN101948468B (en) | Preparation method of quinine hydrochloride | |
| CN108929270B (en) | Synthesis of drug intermediate disubstituted nitrogen heterocyclic ring-containing amine compound | |
| CN111116345A (en) | Novel method for preparing Mirogabalin | |
| CN101139280B (en) | Preparation method of sodium acetate anhydrous | |
| CN112707901B (en) | Preparation method of compound A | |
| CN103435567A (en) | Valsartan refining method | |
| CN1240665C (en) | Process for preparing chicoric acid from echinacea purpurea | |
| CN102417472A (en) | Preparation method of florfenicol | |
| CN108017561B (en) | Method for refining carglutamic acid | |
| CN103374016A (en) | Artesunate purification process | |
| CN102617461A (en) | Novel method for refining aripiprazole | |
| CN103755609B (en) | Crystal formation of tartaric acid valnemulin and preparation method thereof | |
| CN102671213B (en) | Scutellarin prodrug and preparation method thereof | |
| CN102464699A (en) | Method for preparing carbenoxolone sodium | |
| CN104761524A (en) | Compounds and application thereof in preparation of anti-parasitosis drugs | |
| CN114380732A (en) | Preparation method of fluoro-indole carboxylic acid compounds | |
| CN102336701A (en) | Carvedilol sulphate crystals, preparation method and application thereof in medicine | |
| WO2012171377A1 (en) | Crystal forms of asiatic acid trometamol salt and preparation methods thereof | |
| CN103193699B (en) | Novel method for preparing prucalopride intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130904 Termination date: 20160820 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |