CN109053648A - A kind of preparation process of potassium dehydroandrographolide succinate - Google Patents
A kind of preparation process of potassium dehydroandrographolide succinate Download PDFInfo
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- CN109053648A CN109053648A CN201811051489.XA CN201811051489A CN109053648A CN 109053648 A CN109053648 A CN 109053648A CN 201811051489 A CN201811051489 A CN 201811051489A CN 109053648 A CN109053648 A CN 109053648A
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- dehydroandrographolide succinate
- stirring
- potassium
- preparation process
- succinate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation processes of potassium dehydroandrographolide succinate, comprising the following steps: andrographolide and succinic anhydride is added in pyridine, under the protection of inert gas, stirring is warming up to reflux state, and temperature control reacts 4h~6h, after reaction cooling obtained reaction solution；Reaction solution is cooled to 40 DEG C~50 DEG C, is evaporated under reduced pressure, obtains crude product；With methylene chloride to crude product, silicagel column is crossed, is quickly eluted with mobile phase, collects the dehydroandrographolide succinate eluent of purifying, and be evaporated under reduced pressure, obtain pure dehydroandrographolide succinate processed；By pure dehydroandrographolide succinate processed organic alcohol solvent stirring and dissolving, potassium bicarbonate aqueous solution is slowly added dropwise in 30 DEG C~45 DEG C, after drop finishes, stirring obtains mixed solution for 1 hour, organic alcohol solvent is added, and after stirring 3 hours, filtering, it is dry to constant weight to get.The yield of potassium dehydroandrographolide succinate obtained by the present invention is higher, and the quality stability of drug is more preferable, and the market competitiveness is stronger.
Description
Technical field
The invention belongs to drug preparation technical field, the preparation process of specifically a kind of potassium dehydroandrographolide succinate.
Background technique
The good antiviral agent of potassium dehydroandrographolide succinate system one has antipyretic, antiinflammation, is clinically widely used in viral pneumonia
And infection of the upper respiratory tract etc., existing method prepare that resulting dehydroandrographolide succinate yield is relatively low, and quality is steady
It is qualitative poor.
Summary of the invention
To solve the above-mentioned problems in the prior art, the present invention provides a kind of preparation processes of potassium dehydroandrographolide succinate.The system
The yield of potassium dehydroandrographolide succinate obtained by standby technique is higher, and the quality stability of drug is more preferable, and the market competitiveness is stronger.
The technical solution adopted by the present invention is that:
A kind of preparation process of potassium dehydroandrographolide succinate, comprising the following steps:
S1, andrographolide and succinic anhydride are added in pyridine, under the protection of inert gas, stirring is warming up to reflux
State, temperature control react 4h~6h, are cooled to 65 DEG C~75 DEG C after reaction, and reaction solution is made；
S2, the resulting reaction solution of step S1 is cooled to 40 DEG C~50 DEG C, is evaporated under reduced pressure, obtained in dehydration Herba Andrographitis
Ester disuccinic acid half ester grease crude product；
S3, with methylene chloride to the resulting dehydroandrographolide succinate grease crude product of step S2, cross silicon
Rubber column gel column is quickly eluted with mobile phase, collects the dehydroandrographolide succinate eluent of purifying, and carries out decompression steaming
It evaporates, obtains pure dehydroandrographolide succinate processed；
S4, by the resulting pure dehydroandrographolide succinate processed organic alcohol solvent stirring and dissolving of step S3,
Potassium bicarbonate aqueous solution is slowly added dropwise in 30 DEG C~45 DEG C, after drop finishes, stirring obtains mixed solution in 1 hour；
S5, the resulting mixed solution of step S4 is added to organic alcohol solvent, and after stirring 3 hours, filtering is dry to perseverance
It weighs to get potassium dehydroandrographolide succinate is arrived.
Preferably, the inert gas in the step S1 is nitrogen.
Preferably, it is 500:15:0.5 that mobile phase, which is the volume ratio of methylene chloride, methanol and formic acid, in the step S3
Mixed liquor.
Preferably, organic alcohol solvent is dehydrated alcohol in the step S5.
Preferably, dry in the step S5 is forced air drying, drying temperature is 50 DEG C.
Beneficial effects of the present invention are as follows:
The yield that the present invention prepares resulting potassium dehydroandrographolide succinate is higher, with high purity, and the quality stability of drug is more preferable, market competition
Power is stronger.
Specific embodiment
The embodiment of the present invention is described in detail below.
Embodiment 1:
A kind of preparation process of potassium dehydroandrographolide succinate, comprising the following steps:
S1, andrographolide of the 5kg after dry and 5kg succinic anhydride are mixed, is added and blender, reflux condensing tube is housed
It is added in 5L pyridine in thermometer three-necked flask, then in three-necked flask, under the protection of nitrogen, stirring is warming up to reflux state
(115 DEG C of pyridine boiling point), temperature control react 4h, are cooled to 65 DEG C after reaction, and reaction solution is made；
S2, the resulting reaction solution of step S1 is cooled to 40 DEG C, in being evaporated under reduced pressure at this temperature, obtains dehydration punching
Lotus lactone disuccinic acid half ester grease crude product；
S3 plus the resulting dehydroandrographolide succinate grease crude product of 8L methylene chloride dissolving step S2,
The dichloromethane solution for obtaining dehydroandrographolide succinate is spare, weighs 200 mesh silica gel 10kg, carries out dress column,
The dichloromethane solution of spare dehydroandrographolide succinate is subjected to loading, with methylene chloride: methanol: formic acid
The mixed liquor of=500:15:0.5 is eluted, and sampling TLC analysis is collected pure dehydroandrographolide succinate and washed
De- liquid, and be evaporated under reduced pressure, obtain pure dehydroandrographolide succinate processed；
S4, pure dehydroandrographolide succinate processed is added 21L absolute ethyl alcohol and stirring dissolve, in 30 DEG C of conditions
Under, the KHCO3 aqueous solution that 1.31kg concentration is 20% is slowly added dropwise, after drop finishes, stirring obtains mixed solution in 1 hour；
S5, the resulting mixed solution of step S4 is added to 14L dehydrated alcohol, and after stirring 3 hours, filtered, drum at 50 DEG C
Air-dry it is dry to constant weight to get potassium dehydroandrographolide succinate.
It is tested into crossing, the purity of the preparation gained potassium dehydroandrographolide succinate of embodiment 1 is 99.20%, yield 85.0%.
Embodiment 2:
A kind of preparation process of potassium dehydroandrographolide succinate, comprising the following steps:
S1, andrographolide of the 5kg after dry and 5kg succinic anhydride are mixed, is added and blender, reflux condensing tube is housed
It is added in 5L pyridine in thermometer three-necked flask, then in three-necked flask, under the protection of nitrogen, stirring is warming up to reflux state
(115 DEG C of pyridine boiling point), temperature control react 6h, are cooled to 75 DEG C after reaction, and reaction solution is made；
S2, the resulting reaction solution of step S1 is cooled to 50 DEG C, in being evaporated under reduced pressure at this temperature, obtains dehydration punching
Lotus lactone disuccinic acid half ester grease crude product；
S3 plus the resulting dehydroandrographolide succinate grease crude product of 8L methylene chloride dissolving step S2,
The dichloromethane solution for obtaining dehydroandrographolide succinate is spare, weighs 200 mesh silica gel 10kg, carries out dress column,
The dichloromethane solution of spare dehydroandrographolide succinate is subjected to loading, with methylene chloride: methanol: formic acid
The mixed liquor of=500:15:0.5 is eluted, and sampling TLC analysis is collected pure dehydroandrographolide succinate and washed
De- liquid, and be evaporated under reduced pressure, obtain pure dehydroandrographolide succinate processed；
S4, pure dehydroandrographolide succinate processed is added 21L absolute ethyl alcohol and stirring dissolve, in 45 DEG C of conditions
Under, the KHCO3 aqueous solution that 1.31kg concentration is 20% is slowly added dropwise, after drop finishes, stirring obtains mixed solution in 1 hour；
S5, the resulting mixed solution of step S4 is added to 14L dehydrated alcohol, and after stirring 3 hours, filtered, drum at 50 DEG C
Air-dry it is dry to constant weight to get potassium dehydroandrographolide succinate.
It is tested into crossing, the purity of the preparation gained potassium dehydroandrographolide succinate of embodiment 1 is 99.17%, yield 84.5%.
Embodiment 3:
A kind of preparation process of potassium dehydroandrographolide succinate, comprising the following steps:
S1, andrographolide of the 5kg after dry and 5kg succinic anhydride are mixed, is added and blender, reflux condensing tube is housed
It is added in 5L pyridine in thermometer three-necked flask, then in three-necked flask, under the protection of nitrogen, stirring is warming up to reflux state
(115 DEG C of pyridine boiling point), temperature control react 5h, are cooled to 70 DEG C after reaction, and reaction solution is made；
S2, the resulting reaction solution of step S1 is cooled to 45 DEG C, in being evaporated under reduced pressure at this temperature, obtains dehydration punching
Lotus lactone disuccinic acid half ester grease crude product；
S3 plus the resulting dehydroandrographolide succinate grease crude product of 8L methylene chloride dissolving step S2,
The dichloromethane solution for obtaining dehydroandrographolide succinate is spare, weighs 200 mesh silica gel 10kg, carries out dress column,
The dichloromethane solution of spare dehydroandrographolide succinate is subjected to loading, with methylene chloride: methanol: formic acid
The mixed liquor of=500:15:0.5 is eluted, and sampling TLC analysis is collected pure dehydroandrographolide succinate and washed
De- liquid, and be evaporated under reduced pressure, obtain pure dehydroandrographolide succinate processed；
S4, pure dehydroandrographolide succinate processed is added 21L absolute ethyl alcohol and stirring dissolve, in 37 DEG C of conditions
Under, the KHCO3 aqueous solution that 1.31kg concentration is 20% is slowly added dropwise, after drop finishes, stirring obtains mixed solution in 1 hour；
S5, the resulting mixed solution of step S4 is added to 14L dehydrated alcohol, and after stirring 3 hours, filtered, drum at 50 DEG C
Air-dry it is dry to constant weight to get potassium dehydroandrographolide succinate.
It is tested into crossing, the purity of the preparation gained potassium dehydroandrographolide succinate of embodiment 1 is 99.24%, yield 85.4%.
A specific embodiment of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.
Claims (5)
1. a kind of preparation process of potassium dehydroandrographolide succinate, which comprises the following steps:
S1, andrographolide and succinic anhydride are added in pyridine, under the protection of inert gas, stirring is warming up to reflux shape
State, temperature control react 4h~6h, are cooled to 65 DEG C~75 DEG C after reaction, and reaction solution is made；
S2, the resulting reaction solution of step S1 is cooled to 40 DEG C~50 DEG C, is evaporated under reduced pressure, obtains Dehydro and drographolide two
Succinic acid half-ester grease crude product；
S3, with methylene chloride to the resulting dehydroandrographolide succinate grease crude product of step S2, cross silicagel column,
It is quickly eluted with mobile phase, collects the dehydroandrographolide succinate eluent of purifying, and be evaporated under reduced pressure, obtained
To pure dehydroandrographolide succinate processed；
S4, by the resulting pure dehydroandrographolide succinate processed organic alcohol solvent stirring and dissolving of step S3, in 30
DEG C~45 DEG C be slowly added dropwise potassium bicarbonate aqueous solution, after drop finishes, stirring obtains mixed solution in 1 hour；
S5, the resulting mixed solution of step S4 is added to organic alcohol solvent, and after stirring 3 hours, filtering, drying to constant weight, i.e.,
Obtain potassium dehydroandrographolide succinate.
2. a kind of preparation process of potassium dehydroandrographolide succinate according to claim 1, which is characterized in that the indifferent gas in the step S1
Body is nitrogen.
3. a kind of preparation process of potassium dehydroandrographolide succinate according to claim 1, which is characterized in that mobile phase is in the step S3
The volume ratio of methylene chloride, methanol and formic acid is the mixed liquor of 500:15:0.5.
4. a kind of preparation process of potassium dehydroandrographolide succinate according to claim 1, which is characterized in that Organic Alcohol is molten in the step S5
Agent is dehydrated alcohol.
5. a kind of preparation process of potassium dehydroandrographolide succinate according to claim 1, which is characterized in that dry for drum in the step S5
Air-dry it is dry, drying temperature be 50 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116003353A (en) * | 2022-12-13 | 2023-04-25 | 成都通德药业有限公司 | Method for recovering andrographolide from crystallization mother liquor |
Citations (4)
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|---|---|---|---|---|
| CN101245056A (en) * | 2007-02-13 | 2008-08-20 | 中国科学院成都生物研究所 | Method for producing dehydration andrographolide |
| CN102584752A (en) * | 2011-12-27 | 2012-07-18 | 开封制药(集团)有限公司 | Preparation method of andrographolide bulk pharmaceutical |
| CN105732547A (en) * | 2016-03-25 | 2016-07-06 | 重庆莱美药业股份有限公司 | Preparation method of dehydrated andrographolide diacid half ester basic salt |
| CN107857747A (en) * | 2017-10-16 | 2018-03-30 | 广州普星药业有限公司 | A kind of preparation method of potassium dehydroandrographolide succinate |
-
2018
- 2018-09-10 CN CN201811051489.XA patent/CN109053648A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245056A (en) * | 2007-02-13 | 2008-08-20 | 中国科学院成都生物研究所 | Method for producing dehydration andrographolide |
| CN102584752A (en) * | 2011-12-27 | 2012-07-18 | 开封制药(集团)有限公司 | Preparation method of andrographolide bulk pharmaceutical |
| CN105732547A (en) * | 2016-03-25 | 2016-07-06 | 重庆莱美药业股份有限公司 | Preparation method of dehydrated andrographolide diacid half ester basic salt |
| CN107857747A (en) * | 2017-10-16 | 2018-03-30 | 广州普星药业有限公司 | A kind of preparation method of potassium dehydroandrographolide succinate |
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| 周辉 等: "脱水穿心莲内酯二琥珀酸半酯的合成工艺", 《黑龙江科技信息》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116003353A (en) * | 2022-12-13 | 2023-04-25 | 成都通德药业有限公司 | Method for recovering andrographolide from crystallization mother liquor |
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