CN101289516B - Hydroxyethyl pachyman sulfuric acid ester and method for preparing same - Google Patents
Hydroxyethyl pachyman sulfuric acid ester and method for preparing same Download PDFInfo
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- CN101289516B CN101289516B CN2007100176761A CN200710017676A CN101289516B CN 101289516 B CN101289516 B CN 101289516B CN 2007100176761 A CN2007100176761 A CN 2007100176761A CN 200710017676 A CN200710017676 A CN 200710017676A CN 101289516 B CN101289516 B CN 101289516B
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- hydroxyethyl
- hydroxyethyl pachyman
- sulfuric acid
- acid ester
- pachyman
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Abstract
The invention relates to a novel compound of hydroxyethyl pachyman sulfate with the anti-tumor property and the immunocompetence and a method for making the same. The tuchahoe powder which is extracted from a sodium hydroxide solution and the ethylene epoxide perform the hydroxyethylation reaction to obtain the hydroxyethyl pachyman polysaccharides; the hydroxyethyl pachyman polysaccharides and the sulphuric acid esterifying agent chlorosulfuric acid perform the sulphuric acid esterification reaction, thereby obtaining the hydroxyethyl pachyman sulfate. The animal experiment shows that the hydroxyethyl pachyman sulfate has the anti-tumor property and the immunocompetence.
Description
Technical field
The present invention relates to hydroxyethyl pachyman sulfuric acid ester and preparation method thereof, it belongs to chemical field, also belongs to the Natural Medicine Chemistry field.
Background technology
Nearly three during the last ten years; a lot of to the research of Pachymose both at home and abroad; there is not the water-insoluble of anti-tumor activity Pachymose to possess anti-tumor activity and immunoregulation effect in order to make; in that being arranged aspect the molecular structure alteration of Pachymose, multinomial achievement in research delivers; patent report was once arranged; β in the Pachymose (1-6) bonded glucose unit is removed with the Smith degradation method; make pachymaran, again pachymaran is made carboxymethylpachymaran through chemical modification; hydroxyethyl pachyman; the oxidation Pachymose; the sulfonylation Pachymose; the acetylize Pachymose; soluble derivatives such as the plain Pachymose of urea.These new poria polysaccharide water soluble derivatives have had anti-tumor activity and immunocompetence, can make medicine.But these Pachymose derivatives all only contain one and replace group, and the Pachymose derivative that contains hydroxyethyl and two substituted radicals of sulfate group does not appear in the newspapers as yet.
Summary of the invention
The purpose of this invention is to provide and a kind ofly possess antitumor and immunocompetent new compound-hydroxyethyl pachyman sulfuric acid ester and preparation method thereof.
Hydroxyethyl pachyman sulfuric acid ester, its structural formula is:
N=30---600 integer
X=(CH
2CH
2O)
xH or (CH
2CH
2O)
xSO
3H;
Y=(CH
2CH
2O)
yH or (CH
2CH
2O)
ySO
3H;
Z=(CH
2CH
2O)
zH or (CH
2CH
2O)
zSO
3H;
Hydroxyethyl substitution value (molar substitution) MS=0.5～4.0
Sulphating degree DS=0.2～2.5
The integer of x, y, z 0～2
Its preparation method is as follows:
The first step: ethoxyl etherification
Poria powder adds the NaOH aqueous solution room temperature of 0.5～2mol/L and extracts, centrifugal gained Pachymose alkaline solution adds the NaOH solution of 5mol/L～10mol/L, make that NaOH concentration is 10～20% in the solution, cooling, in 0～40 ℃ of oxyethane that slowly drips 1～10 times of weight of Poria powder weight down, stirring at low speed is carried out etherification reaction, dropwises in 24～72 hours.After etherification reaction finishes,, make solution PH=6～8 with hydrochloric acid or acetate neutralization.Remove wherein salt and small molecular weight impurity, molecular weight cut-off 10000 with dialysis or ultrafiltration mode then.Through lyophilize, product is a hydroxyethyl pachyman again, its molar substitution MS=0.5～4.0.
Second step: two kinds of different process of sulfuric acid esterification
1, dried hydroxyethyl pachyman is dissolved in anhydrous solvent methane amide or N, N-dimethyl formamide, or in the pyridine, put in the ice bath, under vigorous stirring, slowly drip HOSO
2Cl, temperature of reaction is controlled at 0～5 ℃, 1～5 hour reaction times, after reaction finishes, with NaOH solution neutralization reaction liquid to PH=6～8.Remove salt and small molecular weight impurity in the reaction solution with dialysis or ultrafiltration process again, molecular weight cut-off 10000, lyophilize promptly gets hydroxyethyl pachyman sulfuric acid ester, and its sulphating degree is DS=0.2～2.5.Described hydroxyethyl pachyman: anhydrous solvent: the ratio of chlorsulfonic acid is 1: 10～20: 0.5～3.5 (weight ratios).
2, hydroxyethyl pachyman is dissolved in the water of 10～20 times of quality, under ice bath, adds in the sulphating reagent of prepared beforehand, under normal temperature, stirring reaction 1～3 hour, control reaction temperature＜30 ℃.Reaction finish the back with NaOH solution neutralization reaction liquid to PH=6～8.Remove salt and small molecular weight impurity (molecular weight cut-off 10000) in the reaction solution with dialysis or ultrafiltration mode again, lyophilize dialyse or ultrafiltration in liquid both must hydroxyethyl pachyman sulfuric acid ester.Its sulphating degree is DS=0.2～2.5.Described hydroxyethyl pachyman: water: the ratio of sulphating agent is 1: 10～20: 4～28 (weight ratios).
The preparation method of sulphating agent under ice bath, slowly drips HOSO
2Cl promptly obtains the sulphating agent in anhydrous solvent, control reaction temperature＜5 ℃.Wherein solvent is N, and N-dimethyl formamide, pyridine etc. contains the organic amine compound of alkyl, and the HOSO2Cl consumption is 10%～30% (volume ratio) of solvent.
The present invention has following technical characterstic
1, for proposing to contain Pachymose derivative--the hydroxyethyl pachyman sulfuric acid ester of hydroxyethyl and these two groups of sulfate group both at home and abroad first.
2, for proposing the preparation method and the technology of this new compound-hydroxyethyl pachyman sulfuric acid ester both at home and abroad first.
3,, thereby the biological activity of new compound and pharmacological function are more promoted and expand because the present invention has introduced hydroxyethyl and these two functional groups of sulfate group in the Pachymose molecule.
Embodiment
Embodiment 1
Poria cocos is pulverized, 80 orders sieve, get powder 116g, extract with the NaOH solution 1500ml stirring at room of 1mol/L, centrifugal back is collected and is seen through liquid, put in the reactor, add the NaOH solution 300ml of 10mol/L, under the stirring at low speed, slowly drip oxyethane and carry out etherification reaction, 1000ml oxyethane dropwised in 72 hours, control reaction temperature＜40 ℃.After reaction finishes, to PH=6～8, put filtering salt and small molecular weight impurity in the ultra-fine filter (or in dialysis mode), molecular weight cut-off 10000 with hydrochloric acid (or acetate) neutralization reaction liquid.Trapped fluid gets hydroxyethyl pachyman 77.8g through lyophilize, hydroxyethyl molar substitution MS=3.1.
Embodiment 2
Get exsiccant hydroxyethyl pachyman 10g, be dissolved in 150ml N, in N-dimethyl formamide, under the ice bath, be cooled to＜5 ℃, slowly drip HOSO under the vigorous stirring
2Cl20ml dropwised in 1 hour, and ice bath is shifted out after dropwising in control reaction temperature＜5 ℃, and normal temperature continued stirring reaction 2 hours down, temperature of reaction＜30 ℃.After reaction finishes, with NaOH solution neutralization reaction liquid to PH=7.Put in the dialysis tubing (or ultrafiltration, molecular weight cut-off 10000), remove salt and small molecular weight impurity.Get hydroxyethyl pachyman sulfuric acid ester 5.8g after the lyophilize, contain S amount 13.63%, DS=1.47.
Embodiment 3
(1) three-necked bottle is put in the ice bath, under the vigorous stirring, with 8ml HOSO
2In the Cl Dropwise 5 0ml pyridine, get white solid, be pyridine N sulfonic acid.
(2) the 5g hydroxyethyl pachyman is dissolved in the 80ml water, splashes in (1) under stirring, normal-temperature reaction 1.5 hours, control reaction temperature＜30 ℃.After reaction finishes,, and in the rearmounted dialysis tubing (or ultrafiltration, molecular weight cut-off 10000), remove salt and small molecular weight impurity with NaOH neutralization reaction liquid PH=7, after the lyophilize, hydroxyethyl pachyman sulfuric acid ester 3.2g, contain S amount 12.45%, DS=1.28.
The hydroxyethyl pachyman sulfuric acid ester that adopts the present invention to make carries out pharmacodynamics test, and the result shows:
(1), can obviously suppress the knurl bulk-growth (P＜0.01) of H22 liver cancer mouse, its tumour inhibiting rate is 35.11%.
(2), can obviously prolong the survival time of EAC ehrlich carcinoma mouse, increase in life span is 61.03%.
(3), can obviously improve the phagocytic function of the reticuloendothelial system of mice with tumor, improve its phagocytic index K (P＜0.01); Can obviously improve the lymphocyte transformation rate (P＜0.01) of tumor-bearing mice; Can obviously improve the tumor-bearing mice sheep red blood cell (SRBC) and cause mouse hemolytic antibody generation (P＜0.05); Can also obviously improve the thymus gland coefficient (P＜0.01) of tumor-bearing mice, but white corpuscle is not had influence.
Evidence, the injection made from hydroxyethyl pachyman sulfuric acid ester, under animal immune hypofunction situation, can the enhance immunity function, improve Abwehrkraft des Koepers, and suppress growth of tumor, the survival time that prolongs mice with tumor simultaneously.
Claims (1)
1. hydroxyethyl pachyman sulfuric acid ester, its structural formula is:
The integer of n=30-600
X=(CH
2CH
2O)
xH or (CH
2CH
2O)
xSO
3H
Y=(CH
2CH
2O)
yH or (CH
2CH
2O)
ySO
3H
Z=(CH
2CH
2O)
zH or (CH
2CH
2O)
zSO
3H
By the mole substitution value, hydroxyethyl substitution value MS=0.5-4.0
Sulphating degree DS=0.2-2.5
The integer of x, y, z 0-2, wherein, x, y and z are not zero simultaneously.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100176761A CN101289516B (en) | 2007-04-16 | 2007-04-16 | Hydroxyethyl pachyman sulfuric acid ester and method for preparing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100176761A CN101289516B (en) | 2007-04-16 | 2007-04-16 | Hydroxyethyl pachyman sulfuric acid ester and method for preparing same |
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| Publication Number | Publication Date |
|---|---|
| CN101289516A CN101289516A (en) | 2008-10-22 |
| CN101289516B true CN101289516B (en) | 2010-09-22 |
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|---|---|---|---|
| CN2007100176761A Expired - Fee Related CN101289516B (en) | 2007-04-16 | 2007-04-16 | Hydroxyethyl pachyman sulfuric acid ester and method for preparing same |
Country Status (1)
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722133B (en) * | 2017-10-30 | 2020-04-17 | 福建农林大学 | Hydroxyethylation method for improving immunocompetence of hericium erinaceus polysaccharide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124249A (en) * | 1994-12-09 | 1996-06-12 | 沈阳药科大学 | Antineoplastic new poria polysaccharide water soluble derivative |
-
2007
- 2007-04-16 CN CN2007100176761A patent/CN101289516B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124249A (en) * | 1994-12-09 | 1996-06-12 | 沈阳药科大学 | Antineoplastic new poria polysaccharide water soluble derivative |
Non-Patent Citations (8)
| Title |
|---|
| J. Hamuro et al..Induction of cytotoxic peritoneal exudate cells by T-cellimmune adjuvants of the β(1→3) glucan-type lentinananditsanalogues.Immunology39 4.1980,39(4),551-557. |
| J. Hamuro et al..Induction of cytotoxic peritoneal exudate cells by T-cellimmune adjuvants of the β(1→3) glucan-type lentinananditsanalogues.Immunology39 4.1980,39(4),551-557. * |
| 吴立根等.衍生化多糖的生物活性研究进展.海洋科学26 5.2002,26(5),23-25. |
| 吴立根等.衍生化多糖的生物活性研究进展.海洋科学26 5.2002,26(5),23-25. * |
| 方波等.磺化羟乙基壳聚糖的研制.中国生化药物杂志19 4.1998,19(4),163-166. |
| 方波等.磺化羟乙基壳聚糖的研制.中国生化药物杂志19 4.1998,19(4),163-166. * |
| 陈春霞.茯苓多糖体的药理药化研究及其临床应用初探.中草药16 4.1985,16(4),40. |
| 陈春霞.茯苓多糖体的药理药化研究及其临床应用初探.中草药16 4.1985,16(4),40. * |
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Assignee: Yunnan Deha Bio-Pharmaceutical Co., Ltd. Assignor: Zheng Mingyi Contract record no.: 2011530000028 Denomination of invention: Hydroxyethyl pachyman sulfuric acid ester and method for preparing same Granted publication date: 20100922 License type: Common License Open date: 20081022 Record date: 20110615 |
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Granted publication date: 20100922 Termination date: 20190416 |