CN108586250A - A kind of sodium stearyl fumarate auxiliary material and preparation method thereof - Google Patents
A kind of sodium stearyl fumarate auxiliary material and preparation method thereof Download PDFInfo
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- CN108586250A CN108586250A CN201810695287.2A CN201810695287A CN108586250A CN 108586250 A CN108586250 A CN 108586250A CN 201810695287 A CN201810695287 A CN 201810695287A CN 108586250 A CN108586250 A CN 108586250A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
- C07C69/593—Dicarboxylic acid esters having only one carbon-to-carbon double bond
- C07C69/60—Maleic acid esters; Fumaric acid esters
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
Abstract
A kind of sodium stearyl fumarate auxiliary material of present invention offer and preparation method thereof, which includes the following steps：S1, maleic anhydride, octadecyl alcolol are mixed with reaction dissolvent, heating carries out ring-opening reaction；S2, transforming agent is added, carries out conversion reaction；The aqueous slkali containing sodium is added dropwise in S3, cooling, and cool down crystallization after being stirred to react, and obtains crude product；S4, refinement treatment is carried out, obtains sodium stearyl fumarate product.The present invention prepares sodium stearyl fumarate using one kettle way, without detaching each intermediate product, greatly simplifies preparation process and post-processing step, reaction condition is mild；Meanwhile total recovery and purity are significantly improved, it is suitable as medicine and food auxiliary material and industrialized production.
Description
Technical field
The invention belongs to auxiliary material preparing technical fields, and in particular to a kind of sodium stearyl fumarate auxiliary material and preparation method thereof.
Background technology
Sodium stearyl fumarate (C22H39NaO4) it is a kind of be widely used and important drug and food auxiliary material.Sodium stearyl fumarate
It in metabolic process in animal body, can largely be absorbed, and hydrolysis generates stearyl alcohol and stearic acid, fraction can be straight
It connects tachymetabolism to go out, with nontoxic nonirritant.In medicine field, sodium stearyl fumarate is added into pharmaceutical preparation
In, the lubricant of tablets and capsules is can be used as, can also form protective film in effervescent tablet, stearates lubrication can be solved
The problems of agent, and improvement medicine disintegration can be played the role of, promote drug-eluting.In field of food, FDA permits stearic
Fumaric acid sodium is directly added into as conditioning agent and stabilizer in the food of human consumption, such as various baked goods, flour thickening
Food, dries the confessions such as potato and processed cereal, and additive amount can account for food weight 0.2~1.0%.
In the prior art, stearyl alcohol and maleic anhydride are usually adopted and prepares hard fumaric acid sodium for raw material, but
It generally requires successively to prepare the intermediate products of various solid-likes in preparation process, it is more not only result in preparation process so, synthesis
Process is cumbersome, and increases production cost and time, can also cause more solvent usage amounts and waste liquid, environmental protection pressure can be more
Greatly, extremely disadvantageous in industrialized production.
Invention content
Technical problem to be solved by the present invention lies in a kind of sodium stearyl fumarate auxiliary material of offer and preparation method thereof, the party
Method synthesis step is simple and has high yield and high-purity.
An aspect of of the present present invention provides a kind of preparation method of sodium stearyl fumarate auxiliary material, includes the following steps：
S1, maleic anhydride, octadecyl alcolol are mixed with reaction dissolvent, under 80 DEG C and temperatures above, carries out ring-opening reaction；
S2, transforming agent is added into reaction system, carries out conversion reaction；
S3, it is cooled to 40-50 DEG C, the aqueous slkali containing sodium is added dropwise into reaction system, cool down crystallization after being stirred to react,
Obtain sodium stearyl fumarate crude product；
S4, refinement treatment is carried out to sodium stearyl fumarate crude product, obtains sodium stearyl fumarate product.
Preferably, in step S1, the reaction dissolvent is one or more in toluene, hexamethylene, normal heptane；It is described to open
The reaction temperature of ring reaction is 80-100 DEG C, and the reaction time is 8-24 hours.
Preferably, in step S2, the transforming agent includes hydrochloric acid/thiourea solution, the hydrochloric acid/thiourea solution by thiocarbamide and
Acid solution is made, and the mass ratio of the thiocarbamide and acid solution is 1:1, the acid solution includes the hydrochloric acid and/or sulphur of 1-12mol/L
Acid；The reaction temperature of the conversion reaction is 70-85 DEG C, and the reaction time is 15-24 hours.
Preferably, in step S3, the aqueous slkali containing sodium includes alkaline constituents and the first solvent, the aqueous slkali containing sodium
The mass percent of middle alkaline constituents is 5-20%, and the alkaline constituents includes the inorganic salts containing sodium.
Preferably, the alkaline constituents is one or more in sodium hydroxide, sodium carbonate, sodium bicarbonate；Described first
Solvent includes water and/or alcohol, and the alcohol is the low-carbon alcohols that carbon atom number is 1~4.
Preferably, the time for adding of the aqueous slkali containing sodium is 0.5-2 hours.
Preferably, in step S4, the refinement treatment, which is included in polar solvent, is beaten purification processes, the polar solvent
For ethyl alcohol, methanol, isopropyl alcohol and water it is one or more.
Preferably, in step S4, the step of refinement treatment, includes：Sodium stearyl fumarate crude product is placed in polar solvent
In, it is beaten 2-10 hours at 40-50 DEG C, successively by stirring, being filtered, washed and dried processing after cooling；The polarity is molten
Agent be ethyl alcohol, methanol, isopropyl alcohol and water it is one or more.
Preferably, the amount ratio of the substance of the maleic anhydride and octadecyl alcolol is 1~1.1, the reaction dissolvent and the horse
The amount ratio for carrying out the substance of acid anhydrides is 4~11；The amount of the substance of the transforming agent is the substance of the maleic anhydride of 5-15%
Amount；The amount ratio of the maleic anhydride and the substance of the alkaline constituents in the aqueous slkali containing sodium is 0.8~1.
Another aspect of the present invention provides a kind of sodium stearyl fumarate, by the preparation method preparation of any description above
.
The present invention at least has the advantages that：
Compared with prior art, the present invention prepares sodium stearyl fumarate using one kettle way, without detaching and purifying each centre
Body, greatly simplifies preparation process and post-processing step, and reaction condition is mild；Meanwhile total recovery is also significantly improved, reduce molten
Agent uses type and scale, and dissolvent residual component is few, and obtained product is purified without column chromatography, you can obtains and is not less than 99%
Purity.Existing preparation process yield is compared to increase, it is more environmentally-friendly, it is suitable as medicine and food auxiliary material and industrial metaplasia
Production.
Description of the drawings
Fig. 1 is the flow chart of the preparation method of the sodium stearyl fumarate auxiliary material in an embodiment of the present invention；
Fig. 2 is the GC collection of illustrative plates of 1 products obtained therefrom of embodiment；
Fig. 3 is the GC collection of illustrative plates of 3 products obtained therefrom of embodiment；
Fig. 4 is the NMR spectra of 3 products obtained therefrom of embodiment；
Fig. 5 is the IR collection of illustrative plates of 3 products obtained therefrom of embodiment.
Specific implementation mode
For a further understanding of the present invention, the preferred embodiment of the invention is described with reference to embodiment, still
It should be appreciated that these descriptions are only the feature and advantage further illustrated the present invention, rather than to the claims in the present invention
Limitation.
All raw materials, reagent below the present invention derive from commercially available.
As shown in Figure 1, the present invention provides a kind of preparation method of sodium stearyl fumarate auxiliary material, include the following steps：
S1, maleic anhydride, octadecyl alcolol are mixed with reaction dissolvent, under 80 DEG C and temperatures above, carries out ring-opening reaction；
S2, transforming agent is added into reaction system, carries out conversion reaction；
S3, it is cooled to 40-50 DEG C, the aqueous slkali containing sodium is added dropwise into reaction system, cool down crystallization after being stirred to react,
Obtain sodium stearyl fumarate crude product；
S4, refinement treatment is carried out to sodium stearyl fumarate crude product, obtains sodium stearyl fumarate product.
It is the process route of the present invention below：
In one embodiment, in step S1, the present invention is molten by using maleic anhydride and octadecyl alcolol as raw material, being placed in reaction
In agent, 80 DEG C or more are warming up under no catalysts conditions, under octadecyl alcolol effect, it is anti-that open loop open loop occurs for maleic anhydride
It answers, generates intermediate compound I.In the present invention, the reaction dissolvent be atent solvent, such as including but not limited to toluene, hexamethylene,
It is one or more in normal heptane, preferably toluene.The reaction temperature of the ring-opening reaction is preferably 80-100 DEG C, further excellent
It is selected as 85-95 DEG C.The reaction time of the ring-opening reaction is 8-24 hours, preferably 10-18 hours.The maleic anhydride and ten
The amount ratio of the substance of eight alcohol is 1~1.2, preferably 1~1.1, further preferably 1.05~1.1.The reaction dissolvent and institute
The amount ratio for stating the substance of maleic anhydride is 3~15, preferably 4~11, further preferably 4~8.
In the present invention, before executing in step S2, the intermediate compound I without being generated to step S1 is individually analysed
Brilliant and purification processes step.
Then, it waits in step S1 after reaction, in step s 2, transforming agent being added into reaction system so that in
Mesosome I isomerization, obtains intermediate II.The transforming agent includes but not limited to thiocarbamide and the thiocarbamide containing acid.The transforming agent
Substance amount be 5-15% the maleic anhydride substance amount, the substance of preferably 10% maleic anhydride
Amount.In the present invention, transforming agent is hydrochloric acid/thiourea solution.Hydrochloric acid/the thiourea solution is made of thiocarbamide and acid solution, specifically
, the hydrochloric acid/thiourea solution can be the physical mixed liquid of thiocarbamide and acid solution.The mass ratio of the thiocarbamide and acid solution is 1:
1.The acid solution includes the hydrochloric acid and/or sulfuric acid of 1-12mol/L, preferably hydrochloric acid solution.The reaction temperature of the conversion reaction
Degree is 70-100 DEG C, preferably 75-88 DEG C, further preferably 80 DEG C.The reaction time of the conversion reaction is 8-36 hours,
Preferably 15-24 hours.
In the present invention, before executing in step S3, the intermediate II without being generated to step S2 carries out individual
Crystallization and purification processes step.
Then, it waits in step S2 after reaction, being cooled to 40-50 DEG C, being preferably down to 40-45 DEG C, to reactant
The aqueous slkali containing sodium is added dropwise in system, produces sodium salt, 20-25 DEG C of crystallization is cooled to after being stirred to react, stearic richness is obtained by filtration
Horse acid sodium crude product.The time for adding of the aqueous slkali containing sodium is 0.5-2 hours.The aqueous slkali containing sodium include alkaline constituents and
First solvent, the alkaline constituents may include the inorganic salts containing sodium, including but not limited in sodium hydroxide, sodium carbonate, sodium bicarbonate
It is one or more.First solvent is the solvent that can dissolve alkaline constituents, preferably water and/or alcohol.Alcohol therein is carbon
The low-carbon alcohols that atomicity is 1~4, including but not limited at least one of methanol, ethyl alcohol, propyl alcohol, butanol and ethylene glycol.It is described
The mass percent of alkaline constituents is 5-20%, preferably 5-15%, further preferably 10% in aqueous slkali containing sodium.The horse
The amount ratio for coming acid anhydrides and the substance of the alkaline constituents in the aqueous slkali containing sodium can be 0.8~1, preferably 0.8-0.95.
In step s 4, refinement treatment is carried out to sodium stearyl fumarate crude product.The refinement treatment is included in polar solvent
Middle mashing purification processes, certainly, the refinement treatment may also include other purification processes steps.In the present invention, described refined
Processing is only mashing purification processes, without progress chromatographic purifying processing, you can obtains the product that purity is not less than 99%.
The specific steps of the refinement treatment include：Sodium stearyl fumarate crude product is placed in polar solvent, at 40-50 DEG C
Lower mashing 2-10 hours after being cooled to 20-25 DEG C, continues stirring 1-3 hours, is filtered, washed and dried processing.The washup
Reason is preferably washed using the common agents such as ethyl alcohol, and plurality of reagents can also be used and alternately wash.The drying
Processing is preferably forced air drying.The polar solvent include but not limited to ethyl alcohol, methanol, isopropyl alcohol and water it is one or more,
Preferably ethyl alcohol.The mass ratio of the polar solvent and sodium stearyl fumarate crude product is 2-20:1, preferably 3-10:1.It is described to stir
It is 20-150rpm, preferably 30-80rpm to mix speed.
The present invention prepares sodium stearyl fumarate using one kettle way, without detaching and purifying each intermediate, greatly simplifies preparation
Process and post-processing step, reaction condition are mild；Meanwhile total recovery is also significantly improved, reduce solvent and uses type and rule
Mould, dissolvent residual component is few, and obtained product is purified without column chromatography, you can obtains the purity not less than 99%.It compares
There is preparation process yield to increase, it is more environmentally-friendly, it is suitable as medicine and food auxiliary material and industrialized production.
In order to further illustrate the present invention, below in conjunction with specific embodiment, the present invention will be described in detail.
The preparation of 1 sodium stearyl fumarate of embodiment
In reaction vessel, 103.0g maleic anhydrides, 270.00g octadecyl alcolols and 1000mL toluene is added, is heated to 85 DEG C instead
After answering 12 hours.Into reaction system, be added 10% hydrochloric acid/thiourea solution (mass ratio of hydrochloric acid and thiocarbamide be 1:1), 80
It is reacted 16 hours at DEG C, through vapor detection：Intermediate II/intermediate compound I is 99.5%.Then, 45 DEG C are cooled to, to reaction system
In, the aqueous solution 320mL of the 51.5g containing sodium hydroxide is added dropwise, is added dropwise after 1 hour, continues stirring 1 hour, is down to room temperature, stirs
It mixes 1 hour, sodium stearyl fumarate crude product is obtained by filtration.The crude product and 2Kg ethyl alcohol are added in reaction vessel, are warming up to 50 DEG C,
And be beaten 7 hours at this temperature, 20 DEG C are cooled to, filtering, ethyl alcohol washs, and obtained solid is dried in vacuo 24 hours, is obtained white
Solid sodium stearyl fumarate 327.6g, yield 83.9%, HPLC purity are 99.24%.
The preparation of 2 sodium stearyl fumarate of embodiment
In reaction vessel, 123.5g maleic anhydride 324.06g octadecyl alcolols and 1200mL hexamethylenes is added, is heated to 90 DEG C instead
After answering 15 hours.Into reaction system, be added 8% hydrochloric acid/thiourea solution (mass ratio of hydrochloric acid and thiocarbamide be 1:1), 72
It is reacted 10 hours at DEG C.Then, 48 DEG C are cooled to, into reaction system, the aqueous solution 650mL of the 49.5g containing sodium hydroxide is added dropwise,
It is added dropwise after 1 hour, continues stirring 1 hour, be down to room temperature, stirred 2 hours, sodium stearyl fumarate crude product is obtained by filtration.It will
The crude product and 4.2Kg ethyl alcohol are added in reaction vessel, are warming up to 50 DEG C, and be beaten 5 hours at this temperature, are cooled to 22 DEG C,
Filtering, ethyl alcohol washing, obtained solid vacuum freeze drying 24 hours obtain white solid sodium stearyl fumarate, yield 82.3%,
HPLC purity is 99.17%.
The preparation of 3 sodium stearyl fumarate of embodiment
In reaction vessel, 10.0kg maleic anhydrides, 26.2kg octadecyl alcolols and 42kg toluene is added, is heated to 85 DEG C of reactions 12
Hour after, be added 10% hydrochloric acid/thiourea solution (mass ratio of hydrochloric acid and thiocarbamide be 1:1) it, reacts 16 hours, passes through at 80 DEG C
Vapor detection:Intermediate II/intermediate compound I is 99.5%.Then, 50 DEG C are cooled to, the aqueous solution of the 4.4kg containing sodium hydroxide is added dropwise
23.8L after 1.5 hours are added dropwise, continues stirring 2 hours, is down to room temperature, stirs 1 hour, sodium stearyl fumarate is obtained by filtration
The crude product and 80kg ethyl alcohol are added in reaction vessel crude product, rise to 50 DEG C, and be beaten 10 hours at this temperature, are cooled to
25 DEG C, filtering, ethyl alcohol washs, and obtained solid is dried in vacuo 24 hours, obtains white solid sodium stearyl fumarate 31.5kg, yield is
83.2%.HPLC purity is 99.94%.
The preparation of 4 sodium stearyl fumarate of embodiment
It is in place of the present embodiment and the difference of embodiment 3：Aqueous solution containing sodium hydroxide is replaced with containing sodium hydroxide
Ethanol solution.
The preparation of 5 sodium stearyl fumarate of embodiment
It is in place of the present embodiment and the difference of embodiment 3：Aqueous solution containing sodium hydroxide is replaced with containing sodium hydroxide
Ethyl alcohol and water mixed solution, wherein the volume ratio of second alcohol and water be 1:2.
6 gas chromatographic detection of embodiment
The detection method and condition of gas chromatographic detection (GC detections) is：Column model：Agilent HP-1 columns
(0.53*15m*0.15μm)；Detector：Fid detector；Column temperature maintains 1 minute at 180 DEG C, with 7 DEG C of heating rate per minute
180 DEG C rise to 320 DEG C, maintain 5 minutes, and carrier gas is helium, and flow velocity is 2mL per minute；250 DEG C of injector temperature, split ratio are
25:1, with flame ionization ditector, detection temperature is 320 DEG C.Take stearic sodium maleate reference substance and sodium stearyl fumarate
Each 1.0mg of reference substance adds silanizing solution [N, bis- (trimethylsilyl) the trifluoroacetamide 2mL of O- to be taken to add trimethyl silane
0.02ml, mixing] 1mL, sealing is heated 1 hour at 70 DEG C, is filtered, accurate to measure 2 μ L injection gas chromatographs of subsequent filtrate, note
Chromatograph figure is recorded, stearic trimethyl silane maleate peak and the separating degree at stearic trimethyl silane fumaric acid peak should be not less than
1.5。
GC tests are carried out to the sodium stearyl fumarate product prepared by embodiment 1 and 3 respectively, test map is respectively as schemed
Shown in 2 and 3, concrete outcome is as follows：
The retention time of each product is determined according to reference substance：Product retention time prepared by embodiment 1 is
11.420min；Product retention time prepared by embodiment 3 is 11.401min.
7 collection of illustrative plates of embodiment detects
Nuclear magnetic resonance (NMR) hydrogen spectrum detection method and condition are：Instrument is Bruker400MHz Nuclear Magnetic Resonance；Solvent is
Deuterated methanol.
NMR tests and IR tests are carried out to the product prepared by embodiment 3, test NMR spectra and IR collection of illustrative plates respectively such as
Shown in Figure 4 and 5.By test result it is found that preparation-obtained product is sodium stearyl fumarate.
8 product testing of embodiment
It is related to European Pharmacopoeia (European Pharmacopoeia 8.0) with reference to United States Pharmacopeia (USP35-NF30)
Method detects 3 gained sodium stearyl fumarate product of embodiment, as a result as follows：
By the above testing result it is found that the indices of preparation-obtained sodium stearyl fumarate meet field of medicaments
Regulation, be suitable as medical auxiliary materials application.
The present invention also provides a kind of sodium stearyl fumarates, are prepared by the preparation method of any description above.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest range caused.
Claims (10)
1. a kind of preparation method of sodium stearyl fumarate auxiliary material, which is characterized in that include the following steps：
S1, maleic anhydride, octadecyl alcolol are mixed with reaction dissolvent, under 80 DEG C and temperatures above, carries out ring-opening reaction；
S2, transforming agent is added into reaction system, carries out conversion reaction；
S3, it is cooled to 40-50 DEG C, the aqueous slkali containing sodium is added dropwise into reaction system, cool down crystallization after being stirred to react, and obtains
Sodium stearyl fumarate crude product；
S4, refinement treatment is carried out to sodium stearyl fumarate crude product, obtains sodium stearyl fumarate product.
2. preparation method according to claim 1, which is characterized in that in step S1, the reaction dissolvent is toluene, hexamethylene
It is one or more in alkane, normal heptane；The reaction temperature of the ring-opening reaction is 80-100 DEG C, and the reaction time is 8-24 hours.
3. preparation method according to claim 1, which is characterized in that in step S2, the transforming agent includes hydrochloric acid/thiocarbamide
Solution, the hydrochloric acid/thiourea solution are made of thiocarbamide and acid solution, and the mass ratio of the thiocarbamide and acid solution is 1:1, the acid
Solution includes the hydrochloric acid and/or sulfuric acid of 1-12mol/L；The reaction temperature of the conversion reaction is 70-85 DEG C, and the reaction time is
15-24 hours.
4. preparation method according to claim 1, which is characterized in that in step S3, the aqueous slkali containing sodium includes alkali
Component and the first solvent, the mass percent of alkaline constituents is 5-20% in the aqueous slkali containing sodium, and the alkaline constituents includes containing
The inorganic salts of sodium.
5. preparation method according to claim 4, the alkaline constituents is in sodium hydroxide, sodium carbonate, sodium bicarbonate
It is one or more；First solvent includes water and/or alcohol, and the alcohol is the low-carbon alcohols that carbon atom number is 1~4.
6. according to any preparation methods of claim 1-5, which is characterized in that the time for adding of the aqueous slkali containing sodium
It is 0.5-2 hours.
7. preparation method according to claim 1, which is characterized in that in step S4, the refinement treatment is included in polarity
Be beaten purification processes in solvent, the polar solvent be ethyl alcohol, methanol, isopropyl alcohol and water it is one or more.
8. preparation method according to claim 1 or claim 7, which is characterized in that in step S4, the step of refinement treatment wraps
It includes：Sodium stearyl fumarate crude product is placed in polar solvent, is beaten 2-10 hours at 40-50 DEG C, successively by stirring after cooling
It mixes, be filtered, washed and dried processing；The polar solvent be ethyl alcohol, methanol, isopropyl alcohol and water it is one or more.
9. preparation method according to claim 1, which is characterized in that the amount ratio of the substance of the maleic anhydride and octadecyl alcolol
It is 1~1.1, the amount ratio of the reaction dissolvent and the substance of the maleic anhydride is 4~11；The amount of the substance of the transforming agent is
The amount 5-15% of the substance of the maleic anhydride；The maleic anhydride and the substance of the alkaline constituents in the aqueous slkali containing sodium
Amount is than being 0.8~1.
10. a kind of sodium stearyl fumarate, which is characterized in that be prepared by any preparation methods of claim 1-9.
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| CN113845423A (en) * | 2021-09-10 | 2021-12-28 | 安徽山河药用辅料股份有限公司 | Pharmaceutic adjuvant sodium stearyl fumarate with uniform sheet-shaped structure and preparation method thereof |
| CN115572225A (en) * | 2022-08-29 | 2023-01-06 | 福建福瑞明德药业有限公司 | Preparation method of sodium stearyl fumarate |
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| CN112624919A (en) * | 2020-10-13 | 2021-04-09 | 南京紫鸿生物科技有限公司 | Low-cost preparation method of pharmaceutic adjuvant sodium stearyl fumarate |
| CN112624919B (en) * | 2020-10-13 | 2023-02-03 | 南京紫鸿生物科技有限公司 | Low-cost preparation method of pharmaceutic adjuvant sodium stearyl fumarate |
| CN113845423A (en) * | 2021-09-10 | 2021-12-28 | 安徽山河药用辅料股份有限公司 | Pharmaceutic adjuvant sodium stearyl fumarate with uniform sheet-shaped structure and preparation method thereof |
| WO2023036273A1 (en) * | 2021-09-10 | 2023-03-16 | 安徽山河药用辅料股份有限公司 | Pharmaceutical excipient sodium stearyl fumarate having uniform lamellar structure and preparation method therefor |
| GB2615932A (en) * | 2021-09-10 | 2023-08-23 | Anhui Sunhere Pharmaceutical Excipients Co Ltd | Pharmaceutical excipient sodium stearyl fumarate having uniform lamellar structure and preparation method therefor |
| CN115572225A (en) * | 2022-08-29 | 2023-01-06 | 福建福瑞明德药业有限公司 | Preparation method of sodium stearyl fumarate |
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