CN104557525B - A kind of preparation method of ester - Google Patents
A kind of preparation method of ester Download PDFInfo
- Publication number
- CN104557525B CN104557525B CN201410556855.2A CN201410556855A CN104557525B CN 104557525 B CN104557525 B CN 104557525B CN 201410556855 A CN201410556855 A CN 201410556855A CN 104557525 B CN104557525 B CN 104557525B
- Authority
- CN
- China
- Prior art keywords
- behenic acid
- glycerol
- acid
- compritol
- ato
- 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)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention provides a kind of preparation method of pharmaceutic adjuvant Compritol 888 ATO, and Compritol 888 ATO is made including reacting in presence of an acid catalyst in mixed reaction solvent in a mixed reaction solvent of cyclohexane and n-heptane in method.Method of the invention can obtain the product for closing symbol pharmaceutic adjuvant quality standard by reaction conditions such as the dosage of control mixed solvent and ratio, reaction temperatures；And easily operated control, it is at low cost, it is suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of preparation methods of pharmaceutic adjuvant, and in particular to the preparation method of Compritol 888 ATO belongs to
Pharmaceutical technology field.
Background technique
Compritol 888 ATO be a kind of predominantly single Compritol 888 ATO (monoesters), two Compritol 888 ATOs (diester) and
The mixture of tribehenin acid glyceride (three esters) is the long-chain fat acid glyceride to serve many purposes；It is a kind of non-ionic
Surfactant has excellent biocompatibility, can be used as lubricant or controlled release agent is used for tablet, capsule, oral solution, can
Improve the compressibility in tablet and capsule manufacture；Also there are the characteristics such as taste masking, chemoproection, anti-oxidation, anti-hydrolysis；It answers extensively
For fields such as food, drug, cosmetics.
In the prior art, the method for preparing Compritol 888 ATO mainly has: with the hydroxyl of protective agent elder generation protected glycerol, then with
Behenic acid (i.e. n-docosane acid) reaction, then hydrolysis deprotection obtain single Compritol 888 ATO；Or using protection
One kettle way obtains single Compritol 888 ATO after the hydroxyl of agent protected glycerol；Or make catalyst using acid, alkali or metal oxide,
And/or pyroreaction, make behenic acid and glycerol direct esterification and obtains Compritol 888 ATO；The product that these methods are prepared
It is either mainly single Compritol 888 ATO or the mixture that pharmaceutic adjuvant requirement is not met for ester content.Behenic acid is positive 20
Two carbon alkanoic acids are a kind of long chain fatty acids, and esterification and the esterification of Short-Chain Fatty Acids have bigger difference；In addition, final product
Color, impurity, content etc. are also vulnerable to the influence of factors.The method of prior art Compritol 888 ATO obtained is difficult to accord with
Close the quality requirement of pharmaceutic adjuvant.The Compritol 888 ATO of high quality plays an important role to pharmaceutical preparation etc.；Therefore, it is necessary to grind
The preparation method of Compritol 888 ATO is studied carefully, to obtain the product for the high quality that can satisfy pharmaceutical preparation requirement.
Summary of the invention
The present invention provides a kind of method for preparing Compritol 888 ATO, and method of the invention, which can obtain, meets pharmaceutic adjuvant
The product of quality standard meets the requirement of preparation, and the easily operated control of method of the invention, at low cost, is suitable for industrialization
Large-scale production.
In European Pharmacopoeia 7.5 editions (European Pharmacopoeia7.5), the quality of pharmaceutic adjuvant Compritol 888 ATO
Ester content, acid value, the specific standards of the parameters such as saponification number are defined in standard；Wherein, to the content range of each ester, it is desirable that Dan Shan
Yu acid glyceride content is 15%-23%, and two Compritol 888 ATO contents are 40%-60%, and tribehenin acid glyceride content is
21%-35%；Acid value is not higher than 4, and saponification number is within the scope of 145-165.
The present invention is intended to provide a kind of easily operated control, at low cost, it is suitable for industrialization large-scale production, symbol can be prepared
The method for closing the Compritol 888 ATO of European Pharmacopoeia standard.
In the present invention, Compritol 888 ATO refers to including single Compritol 888 ATO, two Compritol 888 ATOs, tribehenin acid glycerol
The mixture of ester.
A kind of method preparing Compritol 888 ATO includes: the hybrid reaction of behenic acid and glycerol in hexamethylene and normal heptane
In solvent, in the presence of a catalyst, reaction obtains Compritol 888 ATO.
Inventor has found different types of reaction dissolvent, has biggish shadow to the ester content of final product Compritol 888 ATO
It rings.Inventors have found that the mixed reaction solvent of hexamethylene and normal heptane meets acquisition the final product of pharmaceutic adjuvant quality requirement
It is advantageous.The solvent volume of the hexamethylene and normal heptane ratio is 1:2-1:10.In some embodiments, the ring
The solvent volume of hexane and normal heptane ratio is 1:3-1:5.
Inventor has found that the rate of reaction is related with the dosage of reaction dissolvent, the dosage of the reaction dissolvent are as follows: with behenyl
Mole meter of acid, each mole of behenic acid, reaction dissolvent consumption 350mL-650mL；In some embodiments, it reacts
Solvent usage is 450mL-550mL；In some embodiments, reaction dissolvent consumption 480mL-520mL.
During the reaction, moisture need to be removed to promote the generation of product.In some embodiments, it is removed using water segregator
Moisture is removed, part reaction dissolvent is added in water segregator to maintain the amount of reaction dissolvent in reactor；It is added in water segregator
The amount of reaction dissolvent is limited with being flowed into the reaction dissolvent in water segregator in reactor.
The catalyst be lewis acid catalyst, in some embodiments the catalyst be selected from p-methyl benzenesulfonic acid or
Its hydrate, sodium bisulfate, the concentrated sulfuric acid, or combinations thereof.In some embodiments, the catalyst is p-methyl benzenesulfonic acid
Or its hydrate.
The molar ratio of the catalyst and behenic acid is 0.03:1-0.1:1.In some embodiments, institute
The molar ratio for stating catalyst and behenic acid is 0.055:1-0.065:1；In some embodiments, the catalyst
Molar ratio with behenic acid is 0.058:1-0.062:1.
When inventor also found behenic acid and glycerine reaction, reaction temperature has larger impact to the quality of final product.Reaction
Temperature is excessively high, is also easy to produce impurity, keeps coloured product deeper.The reaction temperature is 80 DEG C -110 DEG C；In some embodiments,
Reaction temperature is 90 DEG C -110 DEG C；In some embodiments, reaction temperature is 93 DEG C -105 DEG C；In some embodiments,
Reaction temperature is the temperature of reaction dissolvent reflux.
When reaction, the molar ratio of behenic acid and glycerol is 1:1-1:2.In some embodiments, behenic acid
Molar ratio with glycerol is 1:1.1-1:1.5；In some embodiments, the molar ratio of behenic acid and glycerol
For 1:1.1-1:1.3.
The reaction time of the behenic acid and glycerol is -15 hours 8 hours.In some embodiments, behenic acid
Reaction time with glycerol is -13 hours 10 hours.
To remove the possibility complete behenic acid of unreacted mixed in product or the behenic acid and other impurity of decomposition,
The quality for improving product, can wash preparation-obtained Compritol 888 ATO, be beaten, crystallization, repeatedly the purifying such as crystallization
Operation.In some embodiments, product is purified using acetone, isopropyl ether, water or combinations thereof.Some specific
In embodiment, product is purified using isopropyl ether.
In some embodiments, a kind of method preparing Compritol 888 ATO includes: behenic acid and glycerol in ring
The in the mixed solvent of hexane and normal heptane, in the presence of p-methyl benzenesulfonic acid, reaction obtains Compritol 888 ATO.
In some embodiments, a kind of method preparing Compritol 888 ATO includes: behenic acid and glycerol in ring
The in the mixed solvent of hexane and normal heptane obtains Compritol 888 ATO in 90 DEG C of -110 DEG C of reactions in the presence of p-methyl benzenesulfonic acid.
In some embodiments, a kind of method preparing Compritol 888 ATO includes: behenic acid and glycerol in ring
The in the mixed solvent of hexane and normal heptane obtains Compritol 888 ATO in 93 DEG C of -105 DEG C of reactions in the presence of p-methyl benzenesulfonic acid；
The volume ratio of the hexamethylene and normal heptane is 1:3-1:5；The molar ratio of p-methyl benzenesulfonic acid or its hydrate and behenic acid
For 0.055:1-0.065:1.
In some embodiments, a kind of method preparing Compritol 888 ATO includes: behenic acid and glycerol in ring
In the mixed reaction solvent of hexane and normal heptane, in the presence of p-methyl benzenesulfonic acid, under reaction dissolvent reflux temperature, reaction is obtained
Compritol 888 ATO；The molar ratio of the behenic acid and glycerol is 1:1.1-1:1.5 or 1:1.1-1:1.3；The ring
The volume ratio of hexane and normal heptane be 1:2-1:10 or 1:3-1:5, mixed reaction solvent dosage by behenic acid mole in terms of, often
One mole of behenic acid, reaction dissolvent consumption are 450mL-550mL or 480mL-520mL；P-methyl benzenesulfonic acid or its hydrate with
The molar ratio of behenic acid is 0.055:1-0.065:1 or 0.058:1-0.062:1；React obtained Compritol 888 ATO
Purified with isopropyl ether.
Preparation method of the present invention, the ester content of the Compritol 888 ATO of acquisition, acid value, saponification number etc. meet Europe
The quality requirement of pharmacopeia can be used for pharmaceutical preparation as pharmaceutic adjuvant；Preparation method of the invention, reaction temperature is low, energy consumption
Low, highly-safe, easily operated control is suitable for industrialized production.
Specific embodiment
For a further understanding of the present invention, the following describes the present invention in detail with reference to examples.Wherein " monoesters " refers to
Single Compritol 888 ATO；" diester " refers to two Compritol 888 ATOs；" three esters " refers to tribehenin acid glyceride.
Embodiment 1
In the reactor, 136.40g behenic acid, 44.60g glycerol, mono- water p-methyl benzenesulfonic acid of 4.60g, hexamethylene is added
With the mixed solvent 200mL (volume ratio 1:4) of normal heptane, same mixed solvent 32mL is added in water segregator, stirs, is heated to
Reflux；Fraction water device water-dividing back flow reaction -12 hours 11 hours, stops reaction；Reaction mixture is cooled to 60 DEG C, is added to
It in 400mL ice water, stirs 1 hour, solid, filtering is precipitated；40 DEG C of obtained solid are dried in vacuo -10 hours 8 hours；Obtained solid
It is mixed with 1000mL isopropyl ether, 20 DEG C -30 DEG C are stirred -1 hour 0.5 hour, filtering, and 35 DEG C of solid vacuum drying 20 are small
When -24 hours；White products 150.35g, HPLC detection are obtained, ester content meets the requirements.
Embodiment 2
In the reactor, 136.40g behenic acid, 44.60g glycerol is added, ring is added in mono- water p-methyl benzenesulfonic acid of 4.60g
Same mixed solvent 30mL is added in water segregator in the mixed solvent 225mL (volume ratio 1:4) of hexane and normal heptane, stirs, adds
Heat extremely flows back；Fraction water device water-dividing back flow reaction -13 hours 12 hours, stops reaction；Mixed liquor is cooled to 60 DEG C, is added to
It in the mixed liquor (volume ratio 1:4) of 450mL cold acetone and water, stirs 1 hour, filtering；40 DEG C of obtained solid vacuum drying 8 are small
When；Obtained solid is mixed with 900mL isopropyl ether, and 25 DEG C -30 DEG C are stirred 1 hour, filtering, and 35 DEG C of solid are dried in vacuo 24 hours；
White products 150.08g, HPLC detection are obtained, ester content meets the requirements.
Embodiment 3
In the reactor, 136.40g behenic acid, 50.00g glycerol is added, ring is added in mono- water p-methyl benzenesulfonic acid of 3.90g
Same mixed solvent 25mL is added in water segregator in the mixed solvent 180mL (volume ratio 1:5) of hexane and normal heptane, stirs, adds
Heat extremely flows back；Fraction water device water-dividing back flow reaction -14 hours 13 hours, stops reaction；Mixed liquor is cooled to 60 DEG C, is added to
It in 400mL cold water, stirs -1.5 hours 1 hour, filtering；40 DEG C of obtained solid are dried in vacuo -10 hours 8 hours；Obtained solid
It is mixed with 1100mL isopropyl ether, 20 DEG C are stirred 45 minutes, filtering, and 35 DEG C of solid are dried in vacuo 24 hours；Obtain white products
149.78g, HPLC detection, ester content meet the requirements.
Reference examples 1
In the reactor, 13.64g behenic acid, 4.46g glycerol is added, positive heptan is added in mono- water p-methyl benzenesulfonic acid of 0.46g
Alkane 20mL, normal heptane 4mL is added in water segregator, and stirring is heated to flowing back；Fraction water device water-dividing, back flow reaction 11 hours -12 are small
When, stop reaction；Mixed liquor is cooled to 60 DEG C, is added in 40mL cold water, is stirred 1 hour, solid, filtering is precipitated；Gained
40 DEG C of solid are dried in vacuo 8 hours；Obtained solid is mixed with 100mL isopropyl ether, and 20 DEG C are stirred 1 hour, filtering, obtained solid 35
DEG C vacuum drying -24 hours 20 hours；Obtain product 15.13g；HPLC detects ester content, monoester content < 15%.
Reference examples 2
In the reactor, 13.64g behenic acid, 4.46g glycerol is added, hexamethylene is added in mono- water p-methyl benzenesulfonic acid of 0.46g
Alkane 20mL, hexamethylene 4mL is added in water segregator, and stirring is heated to flowing back；Fraction water device water-dividing, back flow reaction 11 hours -12 are small
When, stop reaction；Mixed liquor is cooled to 60 DEG C, is added in 40mL cold water, is stirred 1 hour, solid, filtering, gained is precipitated
40 DEG C of solid are dried in vacuo 8 hours；Then obtained solid is mixed with 100mL isopropyl ether, and 20 DEG C are stirred -1 hour 0.5 hour, mistake
Filter, 35 DEG C of solid are dried in vacuo -24 hours 20 hours；Obtain product 15.49g；HPLC detects ester content, monoester content > 23%.
Reference examples 3
In the reactor, 13.64g behenic acid, 4.46g glycerol is added, hexamethylene and positive heptan is added in 0.096g sodium hydroxide
Same solvent 4mL stirring is added in water segregator, is heated to flowing back by the mixed solvent 20mL (volume ratio 1:4) of alkane；Water segregator point
Water, back flow reaction 11 hours, the remaining big content of starting materials (behenic acid surplus > 10%) of HPLC detection discovery；It abandons.
Reference examples 4
In the reactor, 13.64g behenic acid, 4.46g glycerol is added, diformazan is added in mono- water p-methyl benzenesulfonic acid of 0.46g
Benzene 20mL, dimethylbenzene 4mL is added in water segregator, and stirring is heated to 145 DEG C；Fraction water device water-dividing, 145 DEG C of reactions are 11 hours -12 small
When, stop reaction；Mixed liquor is cooled to 60 DEG C, is added in 40mL cold water, is stirred 1 hour, solid, filtering, gained is precipitated
40 DEG C of solid are dried in vacuo -10 hours 8 hours；Then obtained solid is mixed with 100mL isopropyl ether, and 20 DEG C are stirred 0.5 hour -1
Hour, filtering, 35 DEG C of solid are dried in vacuo -24 hours 20 hours；Obtain yellow product 15.49g；HPLC detects ester content, monoesters
Content < 15%.
The ester content of embodiment 4:HPLC detection product
According to the correlation technique of European Pharmacopoeia 7.5 editions (European Pharmacopoeia7.5), requirement, standard, detection
All data.HPLC detects the ester content of each embodiment, reference examples products obtained therefrom, testing conditions are as follows:
Chromatographic column: 7mmx0.6m；Stationary phase: styrene-divinylbenzene copolymer；Partial size: 5 μm；Aperture: 10nm；Flowing
Phase: tetrahydrofuran；Flow velocity: 1mL/min；Detector temperature: 40 DEG C；Column temperature: 40 DEG C；Detector: differential refraction；Sample volume: 40 μ
L (when sample introduction, sample temperature control is at 35 DEG C or ready-to-use).
Testing result is as follows:
| Product ester content (%) | Monoesters | Diester | Three esters | Acid value | Saponification number |
| Acceptable standard (%) | 15.0-23.0 | 40.0-60.0 | 21.0-35.0 | ≤4.0 | 145-165 |
| Embodiment 1 | 21.20 | 49.87 | 27.57 | 0.36 | 149 |
| Embodiment 2 | 20.37 | 50.27 | 26.17 | 0.34 | 148 |
| Embodiment 3 | 20.52 | 49.58 | 26.47 | 0.35 | 148 |
| Reference examples 1 | 12.59 | 63.73 | 21.84 | \ | \ |
| Reference examples 2 | 24.11 | 54.39 | 20.26 | \ | \ |
| Reference examples 4 | 11.81 | 66.09 | 20.97 | \ | \ |
The above description of the embodiment is only used to help understand the method for the present invention and its core ideas.It should be pointed out that pair
For those skilled in the art, without departing from the principle of the present invention, the present invention can also be carried out
Some improvements and modifications, these improvements and modifications also fall within the scope of protection of the claims of the present invention.
Claims (9)
1. a kind of preparation method of Compritol 888 ATO, comprising: the hybrid reaction of behenic acid and glycerol in hexamethylene and normal heptane
It in solvent, in the presence of a catalyst, reacts and obtains Compritol 888 ATO, the volume ratio of the hexamethylene and normal heptane is 1:2-1:
10；Wherein, the molar ratio of behenic acid and glycerol is 1:1-1:2；The catalyst is selected from p-methyl benzenesulfonic acid or its hydration
Object, sodium bisulfate, one of concentrated sulfuric acid or a variety of.
2. according to the method described in claim 1, further including that Compritol 888 ATO is purified with isopropyl ether.
3. the volume ratio of preparation method according to claim 1 or 2, the hexamethylene and normal heptane is 1:3-1:5.
4. preparation method according to claim 1 or 2, the dosage of the mixed reaction solvent, by behenic acid mole in terms of,
Each mole of behenic acid, reaction dissolvent consumption 350mL-650mL.
5. the molar ratio of preparation method according to claim 1 or 2, the catalyst and behenic acid is 0.03:1-
0.1:1。
6. the molar ratio of preparation method according to claim 1 or 2, behenic acid and glycerol is 1:1.1-1:1.5.
7. the reaction temperature of preparation method according to claim 1 or 2, behenic acid and glycerol is 90 DEG C -110 DEG C.
8. the reaction time of preparation method according to claim 1 or 2, behenic acid and glycerol is -15 hours 8 hours.
9. according to the method described in claim 1, including: the mixed reaction solvent of behenic acid and glycerol in hexamethylene and normal heptane
In, in the presence of p-toluenesulfonic acid or its hydrate, behenyl acid glycerol is obtained within -13 hours 10 hours in 90 DEG C of -110 DEG C of reactions
Ester；The molar ratio of the behenic acid and glycerol is 1:1.1-1:1.3；In the mixed reaction solvent, hexamethylene and normal heptane
Volume ratio is 1:3-1:5, mixed reaction solvent dosage by behenic acid mole in terms of, each mole of behenic acid, reaction dissolvent consumption
For 480mL-520mL；The molar ratio of the p-methyl benzenesulfonic acid or its hydrate and behenic acid is 0.058:1-0.062:1；
Obtained Compritol 888 ATO is reacted to be purified with isopropyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410556855.2A CN104557525B (en) | 2013-10-21 | 2014-10-20 | A kind of preparation method of ester |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310495629 | 2013-10-21 | ||
| CN2013104956293 | 2013-10-21 | ||
| CN201410556855.2A CN104557525B (en) | 2013-10-21 | 2014-10-20 | A kind of preparation method of ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104557525A CN104557525A (en) | 2015-04-29 |
| CN104557525B true CN104557525B (en) | 2019-01-04 |
Family
ID=53074708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410556855.2A Active CN104557525B (en) | 2013-10-21 | 2014-10-20 | A kind of preparation method of ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104557525B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417522B (en) * | 2017-05-22 | 2020-11-06 | 武汉桀升生物科技有限公司 | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant |
Citations (2)
| 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 |
| CN103102267A (en) * | 2011-11-10 | 2013-05-15 | 江西阿尔法高科药业有限公司 | Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
-
2014
- 2014-10-20 CN CN201410556855.2A patent/CN104557525B/en active Active
Patent Citations (2)
| 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 |
| CN103102267A (en) * | 2011-11-10 | 2013-05-15 | 江西阿尔法高科药业有限公司 | Preparation method of pharmaceutic adjuvant grade Glyceryl Behenate |
Non-Patent Citations (3)
| Title |
|---|
| Lik H.Wee et al..Synthesis of Monoglycerides by Esterification of Oleic Acid with Glycerol in Heterogeneous Catalytic Process Using Tin-Organic Framework Catalyst.《Catalysis Letters》.2013,第143卷(第4期),第356-363页. |
| Y. Pouilloux et al..Synthesis of glycerol monooctadecanoate from octadecanoic acid and glycerol. Influence of solvent on the catalytic properties of basic oxides.《C. R. Acad. Sci. Paris, Série IIc, Chimie : Chemistry》.2000,第3卷(第7期),第589-594页. |
| 高纯度甘油单酯制备、性质及应用;周曙光;《日用化学工业》;19941231(第3期);第43-44、53页 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104557525A (en) | 2015-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103923024B (en) | A kind of process for purification of acipimox | |
| CN101864019A (en) | Preparation method of sodium polystyrene sulfonate ion exchange resin | |
| CN104203896A (en) | Method for the preparation of triglycerides of medium-chain length fatty acids | |
| CN109575024A (en) | A kind of matrine phenolate and the preparation method and application thereof | |
| CN104557525B (en) | A kind of preparation method of ester | |
| CN104177461A (en) | Preparation method of troxerutin | |
| CN103570530B (en) | A kind of preparation method of anidulafungin side chain intermediate | |
| CN102558124A (en) | Method for preparing food-grade sodium dehydroacetate | |
| CN104892909A (en) | Preparation method of polyethyleneglycol monomethyl ether-polylactic acid block copolymer | |
| CN101891784A (en) | Method for synthesizing 3',4',7-troxerutin | |
| CN102248622A (en) | Capsule mold release agent and preparation method thereof | |
| CN108586250A (en) | A kind of sodium stearyl fumarate auxiliary material and preparation method thereof | |
| CN103420979B (en) | The process for purification of Esomeprazole sodium | |
| CN102277237B (en) | Preparation method of high-purity glyceride type fish oil | |
| CN105175317B (en) | A kind of method for preparing picosulfate sodium | |
| CN110423186A (en) | A method of producing phloroglucin | |
| CN109400432A (en) | The preparation method and application of hydroxytyrosol ester type compound | |
| CN102198402A (en) | Cu-Pd-Mg-Al four-component catalyst for preparing 1,2-propylene glycol (1,2-PDO) by hydrogenation of biodiesel-based crude glycerin as well as preparation method thereof | |
| CN105001256B (en) | The preparation method of Choline Glycerophosphate crystal | |
| CN105175316B (en) | A kind of method for preparing laxative picosulfate sodium | |
| CN108440630A (en) | The preparation process of phytosterols oletate | |
| CN102690212A (en) | Preparation method of iodixanol | |
| CN111574386B (en) | Purification method of oxoethylamine compound | |
| CN107417522B (en) | Method for catalytically synthesizing glyceryl behenate used as pharmaceutical adjuvant | |
| WO2019237327A1 (en) | Method for producing phloroglucinol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Patentee after: Guangdong Dongyangguang Pharmaceutical Co.,Ltd. Address before: 523808 No. 1 Industrial North Road, Songshan Industrial Park, Songshan, Guangdong, Dongguan, Hubei Patentee before: SUNSHINE LAKE PHARMA Co.,Ltd. |