CN106519071A - Synthetic method of antitumor drug 6-hydroxy seleninic acid esterification chitosan copper - Google Patents
Synthetic method of antitumor drug 6-hydroxy seleninic acid esterification chitosan copper Download PDFInfo
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- CN106519071A CN106519071A CN201610937158.0A CN201610937158A CN106519071A CN 106519071 A CN106519071 A CN 106519071A CN 201610937158 A CN201610937158 A CN 201610937158A CN 106519071 A CN106519071 A CN 106519071A
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- copper
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- chitosan copper
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- selenium dioxide
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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Abstract
The invention relates to a synthetic method of an antitumor drug 6-hydroxy seleninic acid esterification chitosan copper. According to the invention, 6-OH is subjected to seleninic acid esterification by a chitosan copper monomer, the chitosan copper is dissolved in an acid solution, the material is added in an seleninic acid aqueous solution, wherein the mol ratio of the chitosan monomer and seleninic acid in the chitosan copper is 1:1, the reaction temperature is controlled between 75-90 DEG C, heating and stirring can be carried out for 2-3 hours to obtain a seleninic acid esterification chitosan copper aqueous solution, ethanol is added until no precipitate is added, the material is filtered, ethanol with concentration of 75% is used for washing for 2-3 times, and drying is carried out to obtain the seleninic acid esterification chitosan copper pure product; and wherein an acid solution is a formic acid or acetic acid aqueous solution with concentration of 1%. The seleninic acid esterification chitosan copper is a preparation which has the advantages of no harm on environment, no toxic and side effect, easy absorption, and containing of selenium and trace element copper, can be taken as a novel selenium and trace element supplement preparation used for the fields of medicine, a health product, a cosmetic and agriculture, and can be taken as the novel antitumor drug.
Description
Technical field
The invention belongs to biomedical engineering technology field, falls within technical field of fine, it is specifically a kind of anti-swollen
Tumor medicine 6- hydroxyls Monohydrated selenium dioxide is esterified the synthetic method of chitosan copper, it is therefore intended that can provide a kind of selenizing site clearly, just
In the chitosan derivatives with anti-tumor activity of production.
Background technology
Shitosan [β (Isosorbide-5-Nitrae) -2- amino -2-DG] is a kind of alkaline biological polyoses, in acid condition
Positively charged, can be neutralized by adsorbing electric discharge with the anion of tumor cell surface, resist its growth, with antitumor,
The multiple biological activities such as antiinflammatory, antibacterial, and biocompatibility is good, almost without toxicity, does not have other untoward reaction, in modern medicine
In thing synthesis, Jing is developed frequently as good drug material, expands its range of application.
。
Selenium is one of required trace element in humans and animals body, and epidemiological studies and vivo and vitro experiment show various
Disease such as tumor, aging, hypoimmunity etc. are all relevant with the scarce selenium of body, and appropriate Selenium Supplement is to improving immunity of organisms, suppressing
Tumor, prevention disease etc. have great significance.But the selenium in nature mostly is inorganic selenium, inorganic Selenium supplement agent such as titanium dioxide is sub-
Selenium, Monohydrated selenium dioxide, sodium selenate etc., its activity are narrower with toxicity range, and bioavailability is relatively low, lethal dose LC50It is relatively small, these
It is restricted its application, therefore searching biological activity is high and the low organic selenium compounds of toxicity just become modern organic selenizing
Learn a vital task of research.
Selenium chitosan is the organic selenium being prepared from using shitosan and Monohydrated selenium dioxide, and early-stage Study result shows that it can
To there is significant Inhibit proliferaton including the kinds of tumor cells including leukaemia and promoting apoptotic effect, low dose of selenium
Change shitosan and still there is certain induction of differentiation, under equal selenium content, selenium chitosan is to NB4 cells and K562 cells
Pharmacological action effect respectively may be about 3 times of sodium selenite and 5 times, and further research shows these pharmacological actions of selenium chitosan
Realized by a plurality of Cell signal propagation pathways in regulating cell, by sequential or be administered simultaneously, selenium chitosan is also
The effect with other clinical Common Chemotherapy medicines is greatly improved, chemotherapeutics using dosage is reduced, the poison of chemotherapeutics is reduced
Side effect, points out selenium chitosan to have a good application prospect.
However, as shitosan is practically insoluble in water, being also practically insoluble in other organic solvents, but can be dissolved in containing inorganic
Acid and some organic aqueous acids, and 2-NH in chitosan molecule2With 6-OH by selenizing after, introduced hydrophilic group and be prepared into
Though the water solublity of selenium chitosan be increased slightly, after the amino in molecule is acylated, amino and organic acid and mineral acid
Affinity weaken so as to dissolubility in an acidic solution is substantially reduced.These limit the use of selenium chitosan.
Chinese invention patent CN1743342A, 2006 chitose sulfuric ester metal complexes and preparation method thereof are proposed, golden
Category ion and ester group are effectively combined with chitosan molecule, can produce synergistic function, and toxicity is low, easy absorption, are had preferably
Water solublity.For this purpose, we are by the shielding action of metal ion, in shitosan 2-NH2Enter with metal ion copper is introduced on 3-OH
Row cyclisation, it is single that Monohydrated selenium dioxide esterification is carried out to 6-OH, both improve selenium chitosan water solublity to reaching, and which is not reduced in nothing
Deliquescent purpose in machine acid and some aqueous solutions of organic acids；Simultaneously because metal ion and Monohydrated selenium dioxide ester group and shitosan point
Son is effectively combined, and not only produces synergistic function, significantly enhances the antioxidation of shitosan and selenium, antibacterial, antitumor and lives
Property, and toxicity is low, easy absorption.But Chinese invention patent CN1685831A is pressed, 2005 chitosan-metal copper complex antimicrobials
Organic/inorganic composite prepared by preparation method [P], not mixing ratio and the clear and definite single compound of structure, it is impossible to
To the compound of single 6-OH Monohydrated selenium dioxides esterification.
The content of the invention
It is an object of the invention to provide a kind of antitumor drug 6- hydroxyls Monohydrated selenium dioxide is esterified the synthetic method of chitosan copper.
The technical scheme is that for this：A kind of antitumor drug 6- hydroxyls Monohydrated selenium dioxide is esterified the synthesis side of chitosan copper
Method, including chitosan copper, it is characterised in that：Described Monohydrated selenium dioxide esterification chitosan copper, is by single on chitosan copper monomer
A pair of 6-OH carry out what Monohydrated selenium dioxide esterification was obtained, and its synthetic method is as follows, and chitosan copper is dissolved in acid solution, is then added to Asia
In selenium aqueous acid, wherein in chitosan copper, the mol ratio ratio of shitosan monomer and Monohydrated selenium dioxide is 1：1, reaction temperature should be controlled
System is in 75-90oBetween C, heated and stirred reacts 2～3 hours to obtain Monohydrated selenium dioxide esterification chitosan copper aqueous solution, adds ethanol to without heavy
Form sediment till producing, filter, and with 75% washing with alcohol 2-3 time, it is dry that Monohydrated selenium dioxide is esterified chitosan copper sterling.
Further it is improved by：Acid solution is 1% formic acid or acetic acid aqueous solution.
Beneficial effect:
Monohydrated selenium dioxide esterification chitosan copper in the present invention is a kind of environmental sound, has no toxic side effect, easily absorbs, rich in selenium and micro-
The preparation of secondary element copper, can be used for medicine, health product, cosmetics and agriculture as the preparation of the new Selenium Supplement of a class and trace element
Industry field, also can be used as a class new type antineoplastic medicine.
Specific embodiment
Citing further illustrates the enforcement of the present invention.
The synthesis of example 1, chitosan copper
Chitosan copper is synthesized according to the method for document, shitosan monomer and Cu in its molecule2+Mol ratio be 1：1.
Example 2, Monohydrated selenium dioxide is esterified the synthesis of chitosan copper
Chitosan copper powder comprising 10mmol shitosan monomers is dissolved in the formic acid or second aqueous acid of 100ml 1%,
10ml is added under agitation dissolved with the water of 10mmol Monohydrated selenium dioxides, controlling reaction temperature 75-90oC, heated and stirred reaction 2～3 are little
When, until Monohydrated selenium dioxide reaction is complete, Monohydrated selenium dioxide esterification chitosan copper aqueous solution is obtained, add ethanol to without precipitation generation, mistake
Filter, and with 75% washing with alcohol 2-3 time, it is dry that Monohydrated selenium dioxide is esterified chitosan copper sterling, by shell in the products molecule that this method synthesizes
Polysaccharide monomer：Cu2+：Se atom=1：1：1（Mol ratio）.
The Monohydrated selenium dioxide esterification chitosan copper of this said method synthesis is that the single 6-OH to shitosan monomer carries out Monohydrated selenium dioxide
Esterification, has reached, and it is molten in mineral acid and some aqueous solutions of organic acids not reduce which
The purpose of solution property, overcomes the shortcomings of inorganic selenium and common selenium chitosan, metallic element copper to have certain collaboration again with selenium
Effect, it suppresses tumor cell proliferation by a plurality of signal transduction pathway in regulating cell, apoptosis-induced, increases tumor cell
Sensitivity to chemotherapeutics, with higher anti-tumor activity.
Claims (2)
1. a kind of antitumor drug 6- hydroxyls Monohydrated selenium dioxide is esterified the synthetic method of chitosan copper, including chitosan copper, and its feature exists
In：Described Monohydrated selenium dioxide esterification chitosan copper, is carried out Monohydrated selenium dioxide to 6-OH and is esterified by single on chitosan copper monomer
Arrive, its synthetic method is as follows, and chitosan copper is dissolved in acid solution, be then added in the aqueous solution of Monohydrated selenium dioxide, wherein shell gathers
In sugared copper, the mol ratio ratio of shitosan monomer and Monohydrated selenium dioxide is 1：1, reaction temperature should be controlled in 75-90oBetween C, heating is stirred
Mix reaction 2～3 hours Monohydrated selenium dioxide esterification chitosan copper aqueous solution, add ethanol to producing without precipitation, filtration, be used in combination
75% washing with alcohol 2-3 time, it is dry that Monohydrated selenium dioxide is esterified chitosan copper sterling.
2. a kind of antitumor drug 6- hydroxyls Monohydrated selenium dioxide according to claim 1 is esterified the synthetic method of chitosan copper, its
It is characterised by：Acid solution is 1% formic acid or acetic acid aqueous solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610937158.0A CN106519071A (en) | 2016-10-25 | 2016-10-25 | Synthetic method of antitumor drug 6-hydroxy seleninic acid esterification chitosan copper |
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| CN201610937158.0A CN106519071A (en) | 2016-10-25 | 2016-10-25 | Synthetic method of antitumor drug 6-hydroxy seleninic acid esterification chitosan copper |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107459582A (en) * | 2017-06-06 | 2017-12-12 | 威海温喜生物科技有限公司 | A kind of preparation method of the polysaccharide selenium copper with bactericidal action |
| CN110563859A (en) * | 2019-09-19 | 2019-12-13 | 湖北医药学院 | One-pot synthesis method and application of anti-liver cancer drug selenite esterified chitosan copper |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6132750A (en) * | 1998-04-14 | 2000-10-17 | Coletica | Particles of cross-linked proteins and polysaccharides with hydroxamic groups for chelating metals and their uses notably in cosmetics |
| CN1284509A (en) * | 2000-07-14 | 2001-02-21 | 武汉大学 | Chitosan selenite and its preparation |
| CN1288899A (en) * | 2000-08-04 | 2001-03-28 | 国家海洋局第一海洋研究所 | Selenium compound of polysaccharide and its preparation |
| CN1685831A (en) * | 2005-04-30 | 2005-10-26 | 武汉大学 | Preparation method of chitin/metal copper composite antibactericidal agent |
| CN1743342A (en) * | 2004-09-01 | 2006-03-08 | 中国科学院海洋研究所 | Sulfated chitosan metal complexes and preparation method thereof |
-
2016
- 2016-10-25 CN CN201610937158.0A patent/CN106519071A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6132750A (en) * | 1998-04-14 | 2000-10-17 | Coletica | Particles of cross-linked proteins and polysaccharides with hydroxamic groups for chelating metals and their uses notably in cosmetics |
| CN1284509A (en) * | 2000-07-14 | 2001-02-21 | 武汉大学 | Chitosan selenite and its preparation |
| CN1288899A (en) * | 2000-08-04 | 2001-03-28 | 国家海洋局第一海洋研究所 | Selenium compound of polysaccharide and its preparation |
| CN1743342A (en) * | 2004-09-01 | 2006-03-08 | 中国科学院海洋研究所 | Sulfated chitosan metal complexes and preparation method thereof |
| CN1685831A (en) * | 2005-04-30 | 2005-10-26 | 武汉大学 | Preparation method of chitin/metal copper composite antibactericidal agent |
Non-Patent Citations (1)
| Title |
|---|
| 孙兰萍，张胜义，许晖: "硒化壳聚糖的制备及理化性质的研究", 《食品工业科技》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107459582A (en) * | 2017-06-06 | 2017-12-12 | 威海温喜生物科技有限公司 | A kind of preparation method of the polysaccharide selenium copper with bactericidal action |
| CN110563859A (en) * | 2019-09-19 | 2019-12-13 | 湖北医药学院 | One-pot synthesis method and application of anti-liver cancer drug selenite esterified chitosan copper |
| CN110563859B (en) * | 2019-09-19 | 2021-07-23 | 湖北医药学院 | One-pot synthesis method and application of anti-liver cancer drug selenite esterified chitosan copper |
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