CN107417522B - Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant - Google Patents
Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant Download PDFInfo
- Publication number
- CN107417522B CN107417522B CN201710363298.6A CN201710363298A CN107417522B CN 107417522 B CN107417522 B CN 107417522B CN 201710363298 A CN201710363298 A CN 201710363298A CN 107417522 B CN107417522 B CN 107417522B
- Authority
- CN
- China
- Prior art keywords
- reaction
- oxide
- glyceryl behenate
- acid
- behenic acid
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a method for catalytically synthesizing glyceryl behenate used as a medicinal auxiliary material, and belongs to the technical field of medicinal auxiliary material synthesis. The method comprises the following steps: adding behenic acid, glycerin and metal oxide into a reaction kettle, heating to 80-150 ℃ under vacuum stirring for dehydration esterification reaction, adding solvents such as ethyl acetate and the like for dissolving after the reaction is finished, neutralizing the catalyst with acid, washing with water, cooling, crystallizing, filtering and drying the obtained organic layer to obtain the product, wherein the solid metal oxide is selected from one or more of zinc oxide, calcium oxide, aluminum oxide, magnesium oxide, iron oxide, copper oxide, barium oxide and titanium dioxide. The method adopts metal oxide to catalyze esterification reaction, the required temperature is low, the reaction time is short, the post-treatment is convenient, the obtained product is pure white powder, all indexes are in pharmacopoeia range, the yield is more than 95%, the operation is simple, and the method is very suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of synthesis of pharmaceutical excipients, in particular to a method for catalytically synthesizing glyceryl behenate used as a pharmaceutical excipient, which takes metal oxide as a catalyst, the synthesized glyceryl behenate simultaneously contains three esters, and the content of the glyceryl behenate is 12-18 percent.
Background
The glyceryl behenate is white powder, is prepared by esterifying behenic acid and glycerol, mainly comprises the mixture of glyceryl behenate, diglyceride behenate and triglyceride behenate, wherein the content of the glyceryl behenate in the glyceryl behenate of the pharmaceutical adjuvant grade is 12% -18%, the acid value is below 4, and the glyceryl behenate is a nonionic surfactant, and has good lubricating, emulsifying and skeleton slow-release properties. Because the lipid-containing nanoparticle is a mixture of three glycerides, long-chain fatty acids are intertwined with each other, and the lipid-containing nanoparticle serving as a carrier material has higher compatibility and encapsulation effect on drugs, and is applied to tablets and capsules as a lubricant in the 80 th century at the earliest, and reports of application to solid lipid nanoparticles, solid lipid particles, nano-structure lipid carriers and sustained-release framework materials are increasing in recent years.
At present, the domestic Jiangxi alpha high-tech pharmaceutical industry Co., Ltd has the production of glyceryl behenate used as a medicinal auxiliary material, but because behenic acid and glycerol are directly esterified at high temperature, activated carbon needs to be added for decolorization, and because the viscosity of the glyceryl behenate is very high, the glyceryl behenate is difficult to filter, and the obtained product has a yellow color. Specifically, patent with application number CN201110355009.0 discloses a preparation method of pharmaceutical adjuvant grade glyceryl behenate, which comprises the following steps: (1) adding behenic acid and glycerol into a reactor, and uniformly stirring, wherein the molar ratio of the behenic acid to the glycerol is 1-2.5: 1; (2) directly heating for dehydration esterification reaction at the temperature of 105-200 ℃ for 5-12 hours; (3) adding active carbon for decoloring and filtering while the solution is hot; (4) cooling, crystallizing, centrifuging, drying, and pulverizing to obtain glyceryl behenate as medicinal adjuvant. The method does not need to add catalysts such as concentrated sulfuric acid, p-toluenesulfonic acid, solid acid and the like during conventional esterification reaction.
In the actual production process, the method has the following problems: the reaction time is too long, the color needs to be decolored if the color is dark, the decoloration is hardly removed in practice, the yield is low, and the acid value is easy to exceed the standard. Therefore, the development of the preparation process of the glyceryl behenate has obvious practical significance for simplifying the treatment method and reducing the production cost to obtain the high-quality glyceryl behenate.
Disclosure of Invention
The invention aims to provide a preparation method of glyceryl behenate, which is simplified and easy to realize and can obtain high-quality and low-price glyceryl behenate. The method comprises the following steps:
the embodiment of the invention provides a method for catalytically synthesizing glyceryl behenate used as a pharmaceutic adjuvant, which comprises the following steps: behenic acid reacts with glycerin under the action of a catalyst to obtain glyceryl behenate. Wherein, the molar ratio of the behenic acid to the glycerol is 1-3:1, the reaction temperature is 80-150 ℃. Wherein, the catalyst is solid metal oxide, and the solid metal oxide is selected from one or more of zinc oxide, calcium oxide, aluminum oxide, magnesium oxide, iron oxide, copper oxide, barium oxide, titanium dioxide and the like. In the esterification process, the used catalyst has good selectivity for catalyzing a target product, and the use of the catalyst ensures that the content of the prepared behenic acid monoglyceride is in a qualified range of 12-18 percent, thereby meeting the requirements of pharmaceutical excipients.
Wherein, the dosage of the catalyst is 0.05 to 5 percent of the total weight of the behenic acid and the glycerol, and is preferably 0.1 to 2 percent.
Preferably, in the present invention, the catalyst is zinc oxide.
Preferably, in the present invention, the reactants are dissolved under the protection of nitrogen, and the reaction is carried out under vacuum condition with the vacuum degree of-0.090 MPa-0.100 MPa. The water generated by the reaction can be pumped away immediately under the vacuum condition, so that the forward reaction is facilitated, and air is isolated to avoid the deep color of the product.
Preferably, in the present invention, the molar ratio of behenic acid to glycerin is 1.5 to 2.2: 1, more preferably 1.6 to 2.0: 1.
in the present invention, the acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid, or the like.
Preferably, in the invention, the catalyst used has good high efficiency for catalyzing target products, and the reaction temperature is 80-150 ℃, preferably 120-140 ℃. The temperature is not lower than the melting point of glyceryl behenate, the system can be normally carried out as a melting liquid reaction, the product quality (mainly comprising color, monoester content, solubility and the like) is not affected when the temperature is higher than 140 ℃, but the temperature is not higher than 140-150 ℃ in consideration of a common steam heating mode.
In the present invention, the reaction time is 1 hour to 8 hours, preferably 3 hours to 8 hours.
Further, after the reaction is finished, cooling to 60-80 ℃, adding an organic solvent which is not soluble in water to dissolve a reaction product, adding acid to regulate the pH value to 6-8 so as to clarify the solution, washing the solution with water (repeatedly washing with purified water) to remove impurities (including a catalyst and the like), taking an organic layer, cooling and crystallizing, centrifuging the organic layer (washing a filter cake to the pH value of about 7), vacuum drying the organic layer and the like to obtain the glyceryl behenate used as the pharmaceutical auxiliary material.
Specifically, the method provided by the invention comprises the following steps:
(1) adding behenic acid, glycerin and solid metal oxide into the reaction kettle, wherein the molar ratio of the behenic acid to the glycerin is 1-3:1 (preferably 1.5-2.2: 1, more preferably 1.6-2.0: 1). Wherein the amount of solid metal oxide is 0.1-5% (preferably 0.1-2%) of the total weight of behenic acid and glycerin, and the solid metal oxide is selected from one or more (preferably zinc oxide) of zinc oxide, calcium oxide, aluminum oxide, magnesium oxide, iron oxide, copper oxide, barium oxide, titanium dioxide, etc.
(2) Replacing the reaction kettle with nitrogen, and stirring at 80-150 ℃ until the materials are melted into clear liquid.
(3) Stopping introducing nitrogen, vacuumizing, keeping the vacuum degree between-0.090 MPa and-0.100 MPa, controlling the reaction temperature to be 80-150 ℃ (preferably 120-140 ℃), controlling the reaction time to be 1-10 hours (preferably 3-8 hours), and continuously pumping out water generated by the reaction.
(4) Slowly cooling to 60-80 ℃, adding an organic solvent into the reaction kettle, stirring to fully dissolve the product, adding acid to adjust the pH value to 6-8 to clarify the solution, and washing with water.
(5) Taking the organic layer, cooling, crystallizing, centrifuging (washing the filter cake to pH of about 7), vacuum drying and the like to obtain the glyceryl behenate used as the pharmaceutic adjuvant.
In the invention, the dosage of the organic solvent is 1-5 times of the total weight of the behenic acid and the glycerol, too little dosage of the product is difficult to completely dissolve, and too much product is incompletely separated out, thus reducing the yield. The organic solvent is selected from ethyl acetate, butyl acetate and the like, and ethyl acetate is preferred.
Wherein, in the invention, the temperature of the cooling crystallization is 0-30 ℃, preferably 10-20 ℃.
In a word, the preparation method adopts the metal oxide to catalyze the esterification of the behenic acid and the glycerol to prepare the glyceryl behenate, the required temperature is low, the reaction time is short, the post-treatment is convenient, the obtained product is white powder, all indexes are in the pharmacopoeia range, the yield is more than 95%, the operation is simple, and the preparation method is very suitable for industrial production.
Detailed Description
The invention is further illustrated by the following examples, but is not limited thereto.
Example 1
34.1 kg of behenic acid, 5.58 kg of glycerol (the molar ratio is 1.65: 1) and 0.4 kg of zinc oxide (1% of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the mixture is heated to 120 ℃ under the protection of nitrogen to be melted into clear transparent liquid, a vacuum pump is started, the pressure is maintained at-0.095 MPa, the reaction is finished after the heat preservation reaction at 120 ℃ is carried out for 3 hours, 200 kg of ethyl acetate is added to dissolve when the temperature is slowly reduced to 70 ℃, hydrochloric acid is added to neutralize the solution until the solution is clear, 20 kg of purified water is used for washing twice, an organic layer is cooled to 15 ℃ to crystallize, centrifugation is carried out, a filter cake is washed to pH =7 by water, and the white powder is dried in vacuum and crushed to obtain 37.20 kg of white powder product, the yield is 98.7%, the melting point is 75 ℃, the acid value is 2.1, the iodine value is.
Comparative example A (No catalyst control)
34.1 kg of behenic acid and 5.58 kg of glycerol (the molar ratio is 1.65: 1) are sequentially put into a 250-liter reaction kettle, the materials are heated to 120 ℃ under the protection of nitrogen and melted into clear and transparent liquid, a vacuum pump is started, the pressure is maintained at-0.095 MPa, the heat preservation reaction is carried out at 120 ℃, the acid value tracking reaction is detected, the reaction system becomes brownish black after 30 hours, the acid value is 13.2, the remaining 10 percent of the behenic acid is not completely reacted, the reaction is continued for 10 hours, the acid value is 10.9, the remaining 8 percent is about 8 percent, the reaction is difficult to completely react within 40 hours, the color is further deepened, and the reaction is not further carried.
Comparative example B (sodium bisulfate as catalyst)
34.1 kg of behenic acid, 5.58 kg of glycerol (molar ratio is 1.65: 1) and 0.4 kg of sodium bisulfate (total input amount is 1%), heating to 120 ℃ under the protection of nitrogen to melt into clear transparent liquid, starting a vacuum pump, maintaining the pressure at-0.095 MPa, carrying out heat preservation reaction at 120 ℃, detecting the acid value to track the reaction, changing the reaction system into a brownish red color after 2 hours, gradually deepening the color along with the time, completely reacting for 21 hours, slowly cooling to 70 ℃, adding 200 kg of ethyl acetate to dissolve, washing to be neutral by using 20 kg of purified water, cooling an organic layer to 15 ℃ to crystallize, centrifuging, and carrying out vacuum drying to obtain 32.5 kg of brownish yellow powder, wherein the yield is 86.4%, the melting point is 70 ℃, the acid value is 3.8, the iodine value is 2.9, the saponification value is 148, and the behenic acid monoglyceride is 13.4%, which indicates that the product obtained under the strong acidic condition is dark in color and low yield.
Example 2
34.1 kg of behenic acid, 5.58 kg of glycerol (molar ratio is 1.65: 1) and 0.6 kg of iron oxide (1.5 percent of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the mixture is heated to 130 ℃ under the protection of nitrogen to be melted into clear transparent liquid, a vacuum pump is started, the pressure is maintained at-0.095 MPa, the temperature of 130 ℃ is kept for reaction, the reaction is finished after 5 hours, 200 kg of ethyl acetate is added for dissolution when the temperature is slowly reduced to 60 ℃, hydrochloric acid is added for neutralization until the solution is clear, 30 kg of purified water is used for washing twice, an organic layer is cooled to 15 ℃ for crystallization, centrifugation is carried out, a filter cake is washed by water until the pH value is =7, and the mixture is dried in vacuum and crushed to obtain 36.7 kg of white powder product, the yield is 96.9%, the melting point is 75 ℃, the acid value is 2.8, the iodine value is 0.8.
Example 3
34.1 kg of behenic acid, 5.58 kg of glycerol (the molar ratio is 1.65: 1) and 0.4 kg of barium oxide (1% of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the mixture is heated to 130 ℃ under the protection of nitrogen to be melted into clear transparent liquid, a vacuum pump is started, the pressure is maintained at-0.095 MPa, the reaction is finished after the heat preservation reaction at 130 ℃ is carried out for 6 hours, 220 kg of ethyl acetate is added to dissolve when the temperature is slowly reduced to 70 ℃, hydrochloric acid is added to neutralize the solution until the solution is clear, 40 kg of purified water is used for washing twice, an organic layer is cooled to 10 ℃ for crystallization, centrifugation is carried out, a filter cake is washed to pH =7 by water, and the white powder product is dried and crushed in vacuum to obtain 36.1 kg of white powder product, the yield is 95.8%, the melting point is 74 ℃, the acid value is 2.7, the iodine value.
Example 4
30.9 kg of behenic acid, 5.58 kg of glycerol (molar ratio is 1.5: 1) and 0.36 kg of zinc oxide (1% of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the mixture is heated to 120 ℃ under the protection of nitrogen to be melted into clear transparent liquid, a vacuum pump is started, the pressure is maintained at-0.095 MPa, the heat preservation reaction is carried out at 130 ℃, 180 kg of ethyl acetate is added for dissolving after the reaction is finished and slowly cooled to 60 ℃ after 5 hours, hydrochloric acid is added for neutralization until the solution is clear, 20 kg of purified water is used for washing twice, an organic layer is cooled to 10 ℃ for crystallization, centrifugation is carried out, a filter cake is washed by water until the pH is =7, and the white powder product is dried in vacuum and crushed to obtain 35.7 kg of white powder product, wherein the yield is 98.3%, the melting point is 74 ℃, the acid value is 2.2, the iodine value is 0.3.
Example 5
39.2 kg of behenic acid, 5.58 kg of glycerol (molar ratio is 1.9: 1) and 0.45 kg of zinc oxide (total input is 1%), heating to 120 ℃ under the protection of nitrogen to melt into clear transparent liquid, starting a vacuum pump, maintaining the pressure at-0.095 MPa, carrying out heat preservation reaction at 120 ℃, slowly cooling to 60 ℃ after 5 hours of reaction, adding 200 kg of ethyl acetate to dissolve, adding hydrochloric acid to neutralize the solution until the solution is clear, washing twice with 20 kg of purified water, cooling an organic layer to 30 ℃ to crystallize, centrifuging, drying in vacuum and crushing to obtain 42.2 kg of white powder product, wherein the yield is 98.5%, the melting point is 75 ℃, the acid value is 2.0, the iodine value is 0.2, the saponification value is 154, and the behenic acid monoglyceride is 13.2%.
Example 6
39.2 kg of behenic acid, 5.58 kg of glycerol (the molar ratio is 1.9: 1) and 0.45 kg of zinc oxide (1% of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the pressure is maintained at-0.095 MPa, the heat preservation reaction is carried out at 100 ℃, 200 kg of ethyl acetate is added for dissolving when the temperature is slowly reduced to 60 ℃ after the reaction is finished after 5.5 hours, hydrochloric acid is added for neutralization until the solution is clarified, 30 kg of purified water is used for washing twice, the organic layer is cooled to 15 ℃ for crystallization, centrifugation, vacuum drying and crushing are carried out, 41.9 kg of white powder products are obtained, the yield is 98.5%, the melting point is 75 ℃, the acid value is 2.2, the iodine value is 0.1, the saponification value is 152, and the behenic acid monoglyceride is 14.3.
Example 7
34.1 kg of behenic acid, 5.58 kg of glycerol (the molar ratio is 1.65: 1) and 0.4 kg of calcium oxide (the total feeding amount is 1%), the pressure is maintained at-0.095 MPa, the temperature is kept at 130 ℃ for reaction, 220 kg of ethyl acetate is added for dissolution when the reaction is finished and the temperature is slowly reduced to 60 ℃ after 4 hours, hydrochloric acid is added for neutralization until the solution is clarified, 30 kg of purified water is used for washing twice, the organic layer is cooled to 15 ℃ for crystallization, centrifugation, vacuum drying and crushing are carried out, 36.0 kg of white powder products are obtained, the yield is 96.2%, the melting point is 73 ℃, the acid value is 3.3, the iodine value is 0.1, the saponification value is 149, and the behenic acid monoglyceride is 16.4%.
Example 8
34.1 kg of behenic acid, 5.58 kg of glycerol (the molar ratio is 1.65: 1) and 0.8 kg of calcium oxide (2 percent of the total feeding amount) are sequentially put into a 250-liter reaction kettle, the pressure is maintained at minus 0.095MPa, the temperature is kept at 130 ℃ for reaction, after 3.5 hours, 220 kg of ethyl acetate is added for dissolving when the reaction is finished and the temperature is slowly reduced to 60 ℃, hydrochloric acid is added for neutralization until the solution is clarified, 30 kg of purified water is used for washing twice, the organic layer is cooled to 5 ℃ for crystallization, centrifugation, vacuum drying and crushing are carried out, 35.8 kg of white powder products are obtained, the yield is 95.7%, the melting point is 75 ℃, the acid value is 3.6, the iodine value is 0.1, the saponification value is 151 and 15.9 percent of behenic acid monoglyceride.
As described above, the above description is only intended to show a plurality of embodiments of the present invention, and it is obvious that those skilled in the art can make partial modifications and variations without departing from the present invention, and the above description is given by way of illustration and not by way of limitation; the catalytic preparation of dichlorohaloalkanes using triethylamine hydrochloride having the characteristics described herein falls within the scope of this patent.
Claims (4)
1. A method for catalytically synthesizing glyceryl behenate for a pharmaceutical excipient, the method comprising:
(1) adding behenic acid, glycerin and solid metal oxide into a reaction kettle, wherein the molar ratio of the behenic acid to the glycerin is 1.6-2.0:1, the dosage of the solid metal oxide is 0.1% -5% of the total weight of the behenic acid and the glycerin, and the solid metal oxide is zinc oxide;
(2) replacing the reaction kettle with nitrogen, and stirring at 80-150 ℃ until the materials are melted into clear liquid;
(3) stopping introducing nitrogen, vacuumizing, keeping the vacuum degree at-0.090 MPa to-0.100 MPa, the reaction temperature at 80-150 ℃, the reaction time at 1-10 hours, and continuously pumping out water generated by the reaction;
(4) cooling to 60-80 ℃, adding an organic solvent into the reaction kettle, stirring to fully dissolve the product, adding acid to adjust the pH value to 6-8, and washing with water;
(5) and (3) taking the organic layer, cooling, crystallizing, centrifuging and drying to obtain the glyceryl behenate used as the pharmaceutic adjuvant.
2. The process for the catalytic synthesis of glyceryl behenate for pharmaceutical excipients according to claim 1, wherein said reaction temperature is between 120 ℃ and 140 ℃.
3. The process for the catalytic synthesis of glyceryl behenate for pharmaceutical excipients according to claim 1, wherein the reaction time is 1 hour to 8 hours.
4. The method for the catalytic synthesis of glyceryl behenate for pharmaceutical excipients according to claim 1, wherein the amount of the organic solvent is 1-5 times of the total weight of the behenate and the glycerol, and the organic solvent is selected from ethyl acetate or butyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710363298.6A CN107417522B (en) | 2017-05-22 | 2017-05-22 | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710363298.6A CN107417522B (en) | 2017-05-22 | 2017-05-22 | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107417522A CN107417522A (en) | 2017-12-01 |
| CN107417522B true CN107417522B (en) | 2020-11-06 |
Family
ID=60427953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710363298.6A Active CN107417522B (en) | 2017-05-22 | 2017-05-22 | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107417522B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558659A (en) * | 2018-04-26 | 2018-09-21 | 武汉桀升生物科技有限公司 | The high-selectivity synthesis method of glycerine monofatty ester |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010120910A (en) * | 2008-11-21 | 2010-06-03 | Kao Corp | Method for producing glycerol monofatty acid ester |
| CN101914014B (en) * | 2010-09-03 | 2013-09-25 | 北京康泰隆科技发展有限公司 | Method for synthesizing and purifying synthetic ester oil for cosmetics and synthetic ester oil for cosmetics obtained by same |
| CN103102267B (en) * | 2011-11-10 | 2015-08-05 | 江西阿尔法高科药业有限公司 | A kind of preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
| CN104557525B (en) * | 2013-10-21 | 2019-01-04 | 广东东阳光药业有限公司 | A kind of preparation method of ester |
-
2017
- 2017-05-22 CN CN201710363298.6A patent/CN107417522B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107417522A (en) | 2017-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2819989B1 (en) | Method for the preparation of triglycerides of medium-chain length fatty acids | |
| US4032702A (en) | Production of surface active material | |
| CN111094312B (en) | Preparation method of sucrose ester | |
| CN109534990B (en) | Method for preparing hindered phenol antioxidant by composite catalyst | |
| CN107417522B (en) | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant | |
| JP2001511186A (en) | Lower alkyl esters reused in the synthesis of polyol fatty acid polyesters | |
| CN101475968B (en) | Method for synthesizing natural alpha-tocofecol tocopherol acid succinate by using lipase | |
| CN107652180A (en) | The production method of tributyrin | |
| CN100345856C (en) | Esterification and crystallizing process for producing glucose halfaldehyde lactone | |
| CN114920642B (en) | Separation process for obtaining high-purity fatty acid monoglyceride and fatty acid diglyceride | |
| CN105566090A (en) | Preparation method for calcium polyunsaturated fatty acid | |
| IE43828B1 (en) | Purification of sucrose esters | |
| CN106542958B (en) | Preparation method of o-iodoaniline | |
| JPWO2008050829A1 (en) | Process for producing S-(-)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and product produced by the process | |
| JP4826133B2 (en) | S-(-)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and process for producing the same | |
| CN103102267B (en) | A kind of preparation method of pharmaceutic adjuvant grade Glyceryl Behenate | |
| CN113527064A (en) | Preparation method of phloroglucinol | |
| CN113402386B (en) | Synthesis method of neopentyl glycol dibenzoate | |
| CN103772241A (en) | Method for preparing sulfonated dehydroabietic acid salt | |
| CN109761801B (en) | Novel method for preparing ketovaline calcium | |
| KR100486860B1 (en) | Recrystallization method of sucrose fatty acid ester | |
| CN105367574A (en) | Process for preparing high purity sinistral leucovorin calcium | |
| JP2016222551A (en) | Purification method of 4-hydroxy benzoic acid long chain ester | |
| JPS6410518B2 (en) | ||
| CN112707828A (en) | Preparation process of trimebutine base |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |