CN1030453C - Process for producing sodium salt of propyl guluronate sulfuric ester - Google Patents
Process for producing sodium salt of propyl guluronate sulfuric ester Download PDFInfo
- Publication number
- CN1030453C CN1030453C CN 88109686 CN88109686A CN1030453C CN 1030453 C CN1030453 C CN 1030453C CN 88109686 CN88109686 CN 88109686 CN 88109686 A CN88109686 A CN 88109686A CN 1030453 C CN1030453 C CN 1030453C
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- China
- Prior art keywords
- ester
- guluronic acid
- propyl
- sodium salt
- acid
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- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a technique for preparing sodium salt of propyl-ester sulfuric ester of guluronic acid, which has the technical scheme that sodium alginate is used as a basic material, and guluronic acid is firstly prepared by steps of acidic hydrolysis, etc., and then, the guluronic acid and the propylene oxide are reacted into guluronic-acid propyl ester through esterification; then, the sodium salt of propyl-ester sulfuric ester of guluronic acid is obtained after sulfonation transformation of chlorosulfuric acid. The sodium salt of propyl-ester sulfuric ester of guluronic acid is a new substance and is also a new heparitin medicine which has no toxin and has the functions of decelerating the growth speed of urine rock salt crystals and preventing crystal accumulation; the sodium salt of propyl-ester sulfuric ester of guluronic acid is particularly suitable for patients with recurrent relapsing calcium calculus of urinary calculus and patients after in-vivo calculus breaking operations.
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 was 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
3, 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, otherwise processed.Centrifugal centrifugate is added alcohol precipitate, promptly get 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
3, 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, precipitation is got its centrifugal sediment with 3000 rev/mins whizzer centrifugation, add ethanol sedimentation and dewater, 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 732,717 cationic, anionic exchange resin desalinations again, alcohol precipitation is used in the back, promptly gets guluronic acid propyl ester sulfuric ester sodium salt.
The ancient sugar ester of being produced among the present invention, its raw material sources are wide, are convenient to mass production, the no three wastes, output and steady quality.It can slow down urinary calculi salt crystalline growth velocity the pharmacological testing proof, prevents the crystalline gathering, and urinary tract mucosa or epithelium are had provide protection.This product is nontoxic, does not have the effect of paying, and irritates stomach with 18～22 gram TWOs and carries out toxicity research, 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, promptly the invention provides a kind of good lithangiuria inhibitor.
Claims (1)
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; Described hydrolysis, be separated under the acidic conditions and carry out, and need boiling water bath to reflux 6～12 hours; Described esterification is meant the guluronic acid that made by hydrolysis and the reaction of propylene oxide, and this is reflected at temperature is 50～80 ℃, pressure 1.5～3kg/cm
2Carry out under the condition, also can adopt the atmospheric pressure reflux method under 40～55 ℃, to carry out, and be catalyzer with NaOH or KoH or sodium ethylate; The guluronic acid propyl ester that makes in the middle of described sulfonation is meant and the reaction of chlorsulfonic acid, wherein solvent is methane amide or pyridine, sulfonation is carried out under 60～80 ℃ of conditions.
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 CN1042360A (en) | 1990-05-23 |
| CN1030453C true 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) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
1988
- 1988-10-30 CN CN 88109686 patent/CN1030453C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1042360A (en) | 1990-05-23 |
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