CN1042360A - Produce the technology of guluronic acid propyl ester sulfuric ester sodium salt - Google Patents
Produce the technology of guluronic acid propyl ester sulfuric ester sodium salt Download PDFInfo
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- CN1042360A CN1042360A CN 88109686 CN88109686A CN1042360A CN 1042360 A CN1042360 A CN 1042360A CN 88109686 CN88109686 CN 88109686 CN 88109686 A CN88109686 A CN 88109686A CN 1042360 A CN1042360 A CN 1042360A
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- guluronic acid
- propyl ester
- acid propyl
- sodium salt
- technology
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- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention is a technology of producing guluronic acid propyl ester sulfuric ester sodium salt.It is basic raw material with the sodium alginate, produce guluronic acid earlier through steps such as acidic hydrolysises, again the latter and propylene oxide reaction esterification are obtained the guluronic acid propyl ester, and then after transforming with the chlorsulfonic acid sulfonation, just obtain guluronic acid propyl ester sulfuric ester sodium salt.This is a kind of novel substance, also is a kind of heparitin new drug.It is nontoxic, can slow down urinary calculi salt crystalline growth velocity, prevents this crystal accumulation, is very suitable for that recurrent that urinary calculi shows effect repeatedly contains the patient of calcium calculus and through the postoperative patient of inside and outside rubble.
Description
The invention belongs to a kind of preparation technology of heparinoid drug.
In recent years, extracorporeal shock-wave lithotomy disease is got carrying out of new technologies such as stone through perverse the wearing of skin, just changing the appearance of urinary calculus clinical treatment, but the elimination of retained calculus and prevent that recurrence of hepatolithiasis etc. is still two hang-ups that clinical urinary calculus treatment is faced also is the problem that solution is concerned about and is pressed for to present pharmacy, medical circle.
Purpose of the present invention just provides a kind of medicine that can eliminate above-mentioned retained calculus and prevent recurrence of hepatolithiasis, i.e. guluronic acid propyl ester sulfuric ester sodium salt (hereinafter to be referred as ancient sugar ester).Known to the inventor, this is a kind of novel substance, and it does not appear in the newspapers especially as the lithangiuria prophylactic agent.It belongs to a kind of polyanion electrolyte, is a kind of heparinoid drug.
A kind of technology of producing guluronic acid propyl ester sulfuric ester sodium salt is disclosed in the present invention.The basic raw material sodium alginate source of producing said medicine by this technology is wide, and this medicine is nontoxic, has the ability that suppresses lithangiuria, is the calculous good medicine of a kind of control.
Because said medicine is not seen before, so its preparation method also is to propose first.
The raw material of producing the gulose ester is a sodium alginate.Known alginic acid molecule is β-D-(1 → 4) the mannopyranose aldehydic acid unit and α-L-(1 → 4 that connect) the unitary linear copolymers of ancient sieve pyranose aldehydic acid that is connected, i.e. M section and G section.They are to replace block by the M-G that accounts for main component to link together.Therefore it is a straight line block compound.
The technological process of producing ancient sugar ester is as follows:
1, produces guluronic acid
Get quantitative food grade sodium alginate, add gauge water and carry out swelling (swelling time is 1～3 day), then add certain density oxalic acid or hydrochloric acid soln with volume, boiling water bath refluxed 6～12 hours, be hydrolyzed, and after-filtration is removed the supernatant liquor sour water.To filter gains with gauge water towards rare, add the solid Na be equivalent to filtrate weight 0.5～1.0%
2CO
2, make it transfer sodium salt to and form colloidal solution, transfer pH to 2～3 with hydrochloric acid again.Quiet heavy, take out supernatant liquor, again with the throw out centrifugation, centrifugate and supernatant liquor lump together, and otherwise processed adds alcohol with centrifugal centrifugate and precipitates, and promptly gets guluronic acid.
2, produce the guluronic acid propyl ester
The above-mentioned guluronic acid airing that makes to containing a certain amount of moisture content, is joined in the retort that fills quantitative propylene oxide in advance, add quantitative NaOH or KOH or sodium ethylate and make catalyzer, at constant temperature (50～80 ℃), level pressure (1.5～3kg/cm
2) act on 2～4 hours down or adopt normal pressure (temperature is 40～55 ℃) circumfluence method to carry out esterification, promptly get the guluronic acid propyl ester.
3, produce guluronic acid propyl ester sulfuric ester sodium salt
With the above-mentioned guluronic acid propyl ester that makes, with methyl alcohol or ethanol repetitive scrubbing, purification, oven dry then, sulfonation under the Yu Zhongwen, sulphonating agent adopts chlorsulfonic acid, and solvent can be with methane amide or N, N=methylformamide or pyridine etc.The sulfonation products therefrom is a guluronic acid propyl ester sulfuric ester, is purified again, and, promptly is converted into sodium salt with the NaOH neutralization, and be exactly guluronic acid propyl ester sulfuric ester sodium salt, also be ancient sugar ester.
Embodiment
1. get food grade sodium alginate 100 grams, add 5000 ml distilled water swellings 24 hours, add 5000 milliliters of 2N oxalic acid again, boiling water bath refluxed 10 hours, filtered, and removed acid solution.Add 3000ml distilled water to filtrate, make its dissolving, and then add solid Na in the ratio of 100 gram solids, 1 gram
2CO
2, making it transfer sodium salt to and become colloidal state, this colloid transfers pH to make it arrive pH=2.85 with 4N HCL, sedimentation precipitates the whizzer centrifugation with 3000 rev/mins, gets its centrifugal sediment, add the ethanol sedimentation dehydration, and airing to water content reaches 40%.Promptly get the guluronic acid raw product.
2. with 100 gram guluronic acids of above-mentioned water content 40%, add the 300ml propylene oxide in autoclave, add 0.6 gram NaOH again at 1.5kg/cm
2Pressure under, 65 ℃ of temperature effect 2 hours, its propyl ester, behind methyl alcohol repetitive scrubbing three times,, promptly get guluronic acid propyl ester dry product in 60 ℃ of oven dry.
3. get guluronic acid propyl ester 100 grams of above-mentioned oven dry, place the 3000ml there-necked flask, add the 1000ml methane amide again, stirring is mixed, slowly drip the 300ml chlorsulfonic acid, temperature is not higher than 5 ℃ in the dropping process, after dripping, makes it be warming up to 65～70 ℃, reacted 3 hours, cooling is filtered, and adds medicinal ethanol sedimentation, the throw out dissolved in distilled water, use ethanol sedimentation again, three times so repeatedly, again after the dissolving, transform with 4N NaOH, use 732 again, 717 sun, the anionite-exchange resin desalination, alcohol precipitation is used in the back, promptly gets guluronic acid propyl ester sulfuric ester sodium salt.
The ancient sugar ester of producing among the present invention, its raw material sources are wide, are convenient to a large amount of productions, the no three wastes, output and steady quality. It can slow down the growth rate of urinary calculi salt crystal the pharmacological testing proof, prevents the gathering of crystal, and urinary tract mucosa or epithelium are had protective effect. This product is nontoxic, does not have the effect of paying, and carries out toxicity research with 18～22 gram TWO gavages, and dosage reaches 5g/kg, and animal subject does not have any toxic reaction. Therefore it is very suitable for recurrent calcic calculus patient that urinary calculi shows effect repeatedly and through the postoperative patient of inside and outside rubble, to eliminate retained calculus and to prevent recurrence of hepatolithiasis, namely the invention provides a kind of good lithangiuria inhibitor.
Claims (4)
1, a kind ofly produces the technology of guluronic acid propyl ester sulfuric ester sodium salt, it is characterized in that earlier with sodium alginate hydrolysis, separation esterification then, sulfonation again by sodium alginate;
2, reparation technology as claimed in claim 1 is characterized in that described hydrolysis, is separated under the acidic conditions and carries out, and needs boiling water bath to reflux 6～12 hours;
3, preparation method as claimed in claim 1 is characterized in that described esterification is meant the guluronic acid that made by hydrolysis and the reaction of propylene oxide, and this is reflected at constant temperature (50～80 ℃), level pressure (1.5～3kg/cm
2) carry out under the condition, also can adopt atmospheric pressure reflux method (40～55 ℃) to carry out, and be catalyzer with NaOH or KOH or sodium ethylate;
4, reparation technology as claimed in claim 1 is characterized in that described sulfonation is meant the middle guluronic acid propyl ester that makes and the reaction of chlorsulfonic acid, and wherein solvent is methane amide or pyridine, and sulfonation is carried out under mesophilic condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 88109686 CN1030453C (en) | 1988-10-30 | 1988-10-30 | Process for producing sodium salt of propyl guluronate sulfuric ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 88109686 CN1030453C (en) | 1988-10-30 | 1988-10-30 | Process for producing sodium salt of propyl guluronate sulfuric ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1042360A true CN1042360A (en) | 1990-05-23 |
| CN1030453C CN1030453C (en) | 1995-12-06 |
Family
ID=4835413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 88109686 Expired - Fee Related CN1030453C (en) | 1988-10-30 | 1988-10-30 | Process for producing sodium salt of propyl guluronate sulfuric ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1030453C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109200058A (en) * | 2017-07-03 | 2019-01-15 | 青岛海洋生物医药研究院股份有限公司 | Guluronic acid propyl ester sulfate is preparing the application in anticoagulation medicine |
-
1988
- 1988-10-30 CN CN 88109686 patent/CN1030453C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109200058A (en) * | 2017-07-03 | 2019-01-15 | 青岛海洋生物医药研究院股份有限公司 | Guluronic acid propyl ester sulfate is preparing the application in anticoagulation medicine |
| CN109200058B (en) * | 2017-07-03 | 2020-09-04 | 青岛海洋生物医药研究院股份有限公司 | Application of poly (propyl guluronate) sulfate in preparation of anticoagulant drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1030453C (en) | 1995-12-06 |
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