CN1470533A - Method for preparing low-molecular-weight chondroitin sulfate - Google Patents
Method for preparing low-molecular-weight chondroitin sulfate Download PDFInfo
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- CN1470533A CN1470533A CNA03114375XA CN03114375A CN1470533A CN 1470533 A CN1470533 A CN 1470533A CN A03114375X A CNA03114375X A CN A03114375XA CN 03114375 A CN03114375 A CN 03114375A CN 1470533 A CN1470533 A CN 1470533A
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Abstract
The preparation method of low molecular weight chondroitin sulfate is characterized by that it utilizes animal soft bone and/or marketable general macromolecular chondroitin sulfate as raw material, and adopts the conventional production process and the special processes of acid hydrolysis, ultrafiltration with ultrafiltration membrane and concentration to obtain the chondroitin sulfate whose molecular weight is less than 1000 daltons. Said product features high purity, good biological activity, high internal biological utilization rate and strong pharmacologic action, etc. and can be used as important raw material of medicine product, health-care product, cosmetics and food.
Description
[technical field]
The present invention relates to a kind of preparation method of low-molecular weight chondroitin sulfate.
[background technology]
Chondroitin sulfate is that a kind of waste material with fishery products such as animal cartilage tissues such as pig, ox, sheep and shark suft bones is starting material, the macromole acidic mucopolysaccharide series products that utilizes biochemical extraction process technology to make.Its sodium salt, sylvite, calcium salt, zinc salt etc. are widely used in medicines and health protection product, food, makeup, feed for pet etc.As hypolipidemic, clinical application chondroitin sulfate sheet treatment hyperlipidemia.Chondroitin sulfate also has different physiological roles, plays an important role keeping function of joint and keeping on the immunity function, is used to prevent and treat neuropathic pains such as coronary heart disease, treatment migraine, improves senile function of joint degeneration etc.
The production method of chondroitin sulfate mainly contains three kinds: salt solution, alkaline hydrolysis method, enzymolysis process: its sodium salt is comparatively common, also can be as required, producing chondroitin sulfate calcium salt, sylvite or zinc salt, is that 99112553.3 " chondroitin sulfate and production methods thereof ", number of patent application are 99112554.1 " chondroitin sulfate and production methods thereof " as number of patent application.
The chondroitin sulfate product is normally about 40 with a kind of molecular weight, 000-50, and 000 daltonian water-soluble polymers form exists, and wherein sulfuric acid is connected on the disaccharides that repeats to combine with ehter bond.Common chondroitin sulfate product is the mixture of two kinds of main configuration chondroitin sulfate A (CSA)s, chondroitin sulfate C.The molecular weight of chondroitin sulfate A (CSA) is 50,000 dalton, and the molecular weight of chondroitin sulfate C is 5,000-50,000 dalton.
The chondroitin sulfate molecular weight difference that the different process method is produced, generally 20,000-50 is between 000 dalton.There are big, the shortcomings such as oral absorption is poor, bioavailability is low, curative effect instability of molecular weight fluctuation in common chondroitin sulfate product.The biological activity of chondroitin sulfate is different and different with molecular weight, its pharmacologically active and molecular weight have confidential relation, U.S. Pat P 3,405,120 have proved that molecular weight is 5,300-3, during 500 dalton, the pharmacologically active of chondroitin sulfate is the strongest, has better therapeutic to preventing and treating atherosclerosis, rheumatic inflammation and wound healing etc.
The preparation method of external existing low-molecular weight chondroitin sulfate comprises acid-hydrolysis method (U.S. Pat P3,405,120), ion-exchange-resin process (Japan special permission 70-04734,74-30817) and enzymolysis process (Japan special permission 73-14078) etc.
At present, China does not still have can be used to produce the Technology of low-molecular weight chondroitin sulfate, and the commercial sulfuric acid chrondroitin does not have molecular weight to be lower than 10,000 daltonian products yet.
[summary of the invention]
The technological method that the present invention relates to is with commercial sulfuric acid chrondroitin (molecular weight 20,000-50,000 dalton) or animal cartilage be raw material, adopt conventional production method, acid hydrolyzation, use ultra-filtration membrane, concentrated, the isolation technique of nanofiltration membrane, the molecular weight of resulting low-molecular weight chondroitin sulfate product can stably be controlled at 10, below 000 dalton, average molecular weight range is 2,000-8,000 dalton.The production process reaction temperature and, the yield height, cost is low, the three wastes are few, easy and simple to handle, technology is reasonable, very suitable suitability for industrialized production.
The present invention adopts ultrafiltration, Nanofiltering membrane grading purification chondroitin sulfate, is the new technique of low-molecular weight chondroitin sulfate suitability for industrialized production, has characteristics such as efficient, energy-conservation, pollution-free.Molecular weight cut-off (MWCO) 10,000 daltonian ultra-filtration membranes can remove macromole impurity such as deproteinize, polysaccharide; Molecular weight cut-off (MWCO) 2,000 daltonian nanofiltration membrane can concentrate, remove small molecular weight impurity.
Preparation method of the present invention, can utilize the different filter membrane of molecular weight cut-off, obtain the low-molecular weight chondroitin sulfate product of different molecular weight ranges, for example molecular weight ranges is 2,000-4,000,4,000-6,000,6,000-8,000,8,000-10,000 daltonian low-molecular weight chondroitin sulfate product.
The low-molecular weight chondroitin sulfate that the present invention produced can be used to produce products such as medicine, healthcare product, makeup, food, animal-feed.
The low-molecular weight chondroitin sulfate that the present invention obtains can according to common process, prepare products such as its sodium salt, sylvite, calcium salt, zinc salt, bismuth salt, magnesium salts, aluminium salt as required.
Low-molecular weight chondroitin sulfate belongs to the bigger product of viscosity, and is comparatively serious to the pollution of ultra-filtration membrane, should select for use polyacrylonitrile, sulfonated polysulfone membrane etc. to be advisable.
The main physical and chemical index of the low-molecular weight chondroitin sulfate that production technique of the present invention makes is as follows:
Proterties: white or off-white powder
Molecular weight: average≤10,000 dalton
Purity: 〉=95%
Weight loss on drying :≤10%
Albumen :≤3.0%
[embodiment]
The following examples are provided,, but do not limit the present invention in any way so that be described in detail scope of the present invention in all fields.
Embodiment 1
1300 liters of deionized waters are placed in the interlayer retort, be heated to 65 ℃, add 30 kilograms of commercial sulfuric acid chrondroitin (molecular-weight average 29,000 dalton) crude product, stirring and dissolving, solution adds 26 liters of 36% hydrochloric acid, add deionized water to 1500 liter, make the concentration of hydrochloric acid of solution be about 0.2N.Insulation and stirring reaction are after 10 hours, and cooling adds 250 liters of 4% aqueous sodium hydroxide solutions rapidly, the pH value that makes solution is about 4.8, with molecular weight cut-off (MWCO) 4,000 daltonian ultrafiltration membrance filters, molecular weight cut-off (MWCO) 2,000 daltonian nanofiltration membrane concentrates, concentrated solution adds 95% ethanol of 7 times of amounts, crystallization, drying, obtain 27.6 kilograms of white low-molecular weight chondroitin sulfates (molecular weight 3,700).
Embodiment 2
1300 liters of deionized waters are placed in the interlayer retort, be heated to 80 ℃, add 30 kilograms of commercial sulfuric acid chrondroitin (molecular-weight average 31,000 dalton) crude product, stirring and dissolving, solution adds 13.5 kilograms of oxalic acid, add deionized water to 1500 liter, make the concentration of oxalic acid of solution be about 0.1N.Insulation and stirring reaction are after 12 hours, and cooling adds 16 kilograms of lime carbonate rapidly, after separating calcium oxalate precipitation, the pH value of solution is about 5.1, with molecular weight cut-off (MWCO) 8,000 daltonian ultrafiltration membrance filter, molecular weight cut-off (MWCO) 2,000 daltonian nanofiltration membrane concentrate, and concentrated solution adds 95% ethanol of 8 times of amounts, crystallization, drying obtains 22.8 kilograms of white low-molecular weight chondroitin sulfates (molecular weight 6,300).
Embodiment 3
650 liters of deionized waters are placed in the interlayer retort, be heated to 73 ℃, add 40 kilograms of commercial sulfuric acid chrondroitins (molecular-weight average 31,000 dalton) crude product, stirring and dissolving, solution adds 11.2 liters of 36% hydrochloric acid, makes the concentration of hydrochloric acid of solution be about 0.2N.Insulation and stirring reaction are after 8.5 hours, and cooling adds 6.8 kilograms of yellow soda ash rapidly, the pH value that makes solution is about 4.6, with molecular weight cut-off (MWCO) 6,000 daltonian ultrafiltration membrance filters, molecular weight cut-off (MWCO) 2,000 daltonian nanofiltration membrane concentrates, concentrated solution adds 95% ethanol of 7 times of amounts, crystallization, drying, obtain 37 kilograms of white low-molecular weight chondroitin sulfates (molecular weight 4,400).
Embodiment 4
According to a conventional method by the animal cartilage of pulverizing, after alkaline extraction, acid neutralization, enzymic hydrolysis, add 36% hydrochloric acid, under 35-95 ℃ condition, acid hydrolysis 3-12 hour, macromole impurity, nanofiltration (molecular weight cut-off 2 are removed in ultrafiltration (molecular weight cut-off 10,000 dalton or less than 10,000 dalton), 000 dalton) concentrate after, precipitate, dehydration, drying, can obtain molecular-weight average less than 10,000 daltonian low-molecular weight chondroitin sulfate products.
Claims (8)
1. the preparation method of a low-molecular weight chondroitin sulfate is characterized in that the molecular weight of the low-molecular weight chondroitin sulfate that obtains is lower than 10,000 dalton.
2. preparation method according to claim 1 is characterized in that the molecular weight ranges of the low-molecular weight chondroitin sulfate that obtains is 8,000-2,000 dalton.
3. preparation method according to claim 1 is characterized in that utilizing animal cartilage and/or commercially available common macromolecule chondroitin sulfate, through acidolysis, ultra-filtration membrane separate, nanofiltration membrane concentrates and process such as crystallization.
4. preparation method according to claim 1, it is characterized in that utilizing molecular weight cut-off is 10,000 daltonian ultra-filtration membranes, removes impurity such as protein in the low-molecular weight chondroitin sulfate, macromolecular polysaccharide.
5. preparation method according to claim 1, it is characterized in that utilizing molecular weight cut-off is 2,000 daltonian nanofiltration membrane, and low-molecular weight chondroitin sulfate is concentrated, removes small molecular weight impurity.
6. preparation method according to claim 1, it is characterized in that the filter membrane that utilizes molecular weight cut-off different, can obtain the low-molecular weight chondroitin sulfate product of different molecular weight ranges, include but not limited to that molecular weight ranges is 2,000-4,000,4,000-6,000,6,000-8,000,8,000-10,000 daltonian low-molecular weight chondroitin sulfate product.
7. preparation method according to claim 1 is characterized in that the low-molecular weight chondroitin sulfate that obtains can be used for producing but is not limited to products such as medicine, healthcare product, makeup, food, animal-feed.
8. preparation method according to claim 1 is characterized in that the low-molecular weight chondroitin sulfate that obtains can be but is not limited to its sodium salt, sylvite, calcium salt, zinc salt, bismuth salt, magnesium salts, aluminium salt.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA03114375XA CN1470533A (en) | 2003-05-07 | 2003-05-07 | Method for preparing low-molecular-weight chondroitin sulfate |
| CNB2003101193037A CN1307203C (en) | 2003-05-07 | 2003-12-03 | Method fo preparing medium, low molecular weight chondroitin sulphate and obtained product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA03114375XA CN1470533A (en) | 2003-05-07 | 2003-05-07 | Method for preparing low-molecular-weight chondroitin sulfate |
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| CN1470533A true CN1470533A (en) | 2004-01-28 |
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| CNA03114375XA Pending CN1470533A (en) | 2003-05-07 | 2003-05-07 | Method for preparing low-molecular-weight chondroitin sulfate |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007131424A1 (en) * | 2006-04-26 | 2007-11-22 | Lijun Zhou | Method for preparing low molecular weight proteoglycan and collagen compositions, its products and uses |
| CN100389777C (en) * | 2003-08-19 | 2008-05-28 | 汤毅 | Moderate molecular weighted chondroitin sulfate injection and its preparing process |
| CN101583338B (en) * | 2006-12-26 | 2012-05-23 | 罗马诺发展公司 | Skin lightening composition for hyperpigmented skin |
| CN104004114A (en) * | 2014-06-06 | 2014-08-27 | 嘉兴纽迪康生物科技有限公司 | Preparation method of low-molecular-weight chondroitin sulfate |
| CN106009068A (en) * | 2016-06-25 | 2016-10-12 | 仇颖超 | Preparation method of hyaluronic acid grafted micromolecular chondroitin sulfate composite |
| CN111662394A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Semi-synthesis preparation method and application of chondroitin sulfate polysaccharide |
-
2003
- 2003-05-07 CN CNA03114375XA patent/CN1470533A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100389777C (en) * | 2003-08-19 | 2008-05-28 | 汤毅 | Moderate molecular weighted chondroitin sulfate injection and its preparing process |
| WO2007131424A1 (en) * | 2006-04-26 | 2007-11-22 | Lijun Zhou | Method for preparing low molecular weight proteoglycan and collagen compositions, its products and uses |
| CN101583338B (en) * | 2006-12-26 | 2012-05-23 | 罗马诺发展公司 | Skin lightening composition for hyperpigmented skin |
| CN104004114A (en) * | 2014-06-06 | 2014-08-27 | 嘉兴纽迪康生物科技有限公司 | Preparation method of low-molecular-weight chondroitin sulfate |
| CN106009068A (en) * | 2016-06-25 | 2016-10-12 | 仇颖超 | Preparation method of hyaluronic acid grafted micromolecular chondroitin sulfate composite |
| CN111662394A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Semi-synthesis preparation method and application of chondroitin sulfate polysaccharide |
| CN111662394B (en) * | 2019-03-05 | 2022-11-04 | 中国医学科学院药物研究所 | Semi-synthetic preparation method and application of chondroitin sulfate polysaccharide |
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