CN1542022A - Carboxybutyryl chitosan sulfuric ester and preparation method and use thereof - Google Patents
Carboxybutyryl chitosan sulfuric ester and preparation method and use thereof Download PDFInfo
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- CN1542022A CN1542022A CNA2003101113297A CN200310111329A CN1542022A CN 1542022 A CN1542022 A CN 1542022A CN A2003101113297 A CNA2003101113297 A CN A2003101113297A CN 200310111329 A CN200310111329 A CN 200310111329A CN 1542022 A CN1542022 A CN 1542022A
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- sulfated chitosan
- chitosan
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Abstract
The present invention discloses carboxyl butyryl chitosan sulfate. It is prepared through dissolving chitosan sulfate with sulfur content of 3-20 wt% and molecular weight of 5000-20000 in distilled water to obtain 5-30 wt% concentration chitosan sulfate aqua in homogeneous phase condition; adding succinic anhydride, mixing and reaction through stirring at 20-30 deg.c; dialysis and freeze drying to obtain carboxyl butyryl chitosan sulfate. The present invention has the advantages of mild reaction condition, easily controlled carboxyl substituting degree, less side reaction, high selectivity, etc. The carboxyl butyryl chitosan sulfate of the present invention has very high anticoagulant activity and may be used in preparing blood coagulation resisting medicine.
Description
Technical field
The present invention relates to carboxylic butyryl radicals sulfated chitosan and method for making thereof and purposes.It belongs to technical field of organic chemistry, also belongs to biochemical field.
Background technology
Sulfated chitosan has tangible anticoagulant active, and being expected to replace heparin becomes a kind of novel anticoagulation medicine (J.Doczi, A.Fishman, amd j.A King, J.Am.chem.Soc., 75 (1953), 1521-1513), and the introducing of carboxyl can promote its anticoagulant active.The reported in literature restraining effect that the carboxymethyl chitosan sugar sulfate transforms to scleroproein Fibrinogen when carboxyl/sulfonic group is about 1: 1 even greatly strengthen (S.Nishimura, N.Nishi.S.Tokurn, Carbohydr.Res., 156 (1986): 286-292).The way of introducing carboxyl at present in sulfated chitosan has two kinds: the one, and chitosan generates cm-chitosan with the chloroformic acid reaction under alkaline condition, generate the carboxymethyl chitosan sugar sulfate through sulphating again; The 2nd, chitosan is through C
6The position selective oxidation reaction generates the oxidation chitosan, generates the carboxyl sulfated chitosan through sulphating again.Because sulfuric acid esterification is out-phase reaction, group such as carboxymethyl has changed the dispersal behavior of sulfonated reagent in the polysaccharide molecule chain in the reaction process, makes sulfonation reaction be difficult for carrying out; The carboxyl phenomenon of dissociating also can take place in the sulfuric acid esterification simultaneously.
Summary of the invention
The present invention is exactly at above-mentioned deficiency; one class new compound-carboxylic butyryl radicals sulfated chitosan and its production and use is provided; gained carboxylic butyryl radicals sulfated chitosan is compared with sulfated chitosan has higher anticoagulant active, can be used for preparing anticoagulation medicine.
For achieving the above object, the technical measures that the present invention taked are as follows:
Carboxylic butyryl radicals sulfated chitosan, its structural formula is:
R in the formula
1, R
2, R
3For-COCH
2CH
2COONa ,-SO
3Na or-H; Wherein-SO
3The substitution value of Na≤3 and greater than 0 ,-COCH
2CH
2The substitution value of COONa is 0.18-0.77; N is 15～50.
Its preparation method is as follows:
Under the homogeneous phase condition; the sulfated chitosan of sulphur content 3～20wt%, molecular weight 5000～20000 is dissolved in the chitosan sulfate aqueous solution of ester that makes 5～30wt% in the distilled water; adding sulfated chitosan sugar unit and Succinic anhydried mol ratio and be 0.2～0.8 Succinic anhydried mixes; behind 20～30 ℃ of stirring reactions, promptly obtain carboxylic butyryl radicals sulfated chitosan through the dialysis lyophilize.
Technological core of the present invention is to introduce carboxyl by sulfated chitosan under the homogeneous phase condition and positive Succinic anhydried reaction.
According to technical scheme of the present invention, described sulfated chitosan substrate comprises different sulfate group content and sulfate group the position of substitution, and its structural formula is
R in the formula
1, R
2, R
3For-COCH
2CH
2COONa ,-SO
3Na or-H; Wherein-SO
3The substitution value of Na≤3 and greater than 0 ,-COCH
2CH
2The substitution value of COONa is 0.18-0.77; N is 15～50.
According to technical scheme of the present invention, the preparation process condition of band carboxyl sulfated chitosan with best anticoagulant active is as follows: 25 ℃ of temperature of reaction, sulfated chitosan sulphur content 13.82% (weight percent), sugar unit is 0.6 with the mol ratio of positive Succinic anhydried, the concentration 20% (weight percent) of sulfated chitosan.
The carboxylic butyryl radicals sulfated chitosan activated partial thromboplastin time that mensuration obtains, thrombin time and prothrombin time, the result shows that its anticoagulant active is higher than corresponding sulfated chitosan, can be used for preparing anticoagulation medicine.
The present invention has following technical characterstic and advantage:
1. for proposing a kind of new compound carboxylic butyryl radicals sulfated chitosan both at home and abroad first.
2. for to propose first under the homogeneous phase condition through the novel method of sulfated chitosan both at home and abroad through carboxylic butyryl radicals introducing carboxyl.
3. new compound carboxylic butyryl radicals sulfated chitosan is compared with sulfated chitosan has higher anticoagulant active.
4. the novel method of introducing carboxyl in sulfated chitosan has the reaction conditions gentleness, and the carboxyl substituted degree is easy to control, and side reaction is few, good selective.
Embodiment
Below in conjunction with embodiment, the technology of the present invention is described in further detail.
Embodiment 1
To be dissolved in 20ml pH be (I=1mol/L) in 9.0 the NaOH/ glycine buffer 4.20g sulphur content is the sulfated chitosan of 16.87% (weight ratio), stirring at room, divide secondary to add 0.6g Succinic anhydried (sulfated chitosan sugar unit and Succinic anhydried mol ratio 0.6) restir 24h, regulate pH to 9.0～10.0; Reaction solution was put into dialysis tubing dialysis 3 days, concentrate brown ceramic powder 0.5g, be N-carboxylic butyryl radicals sulfated chitosan.The ultimate analysis substitution value is 0.77mol/unit, and gel chromatography proof molecular weight and sulfated chitosan difference are very little, do not have signs of degradation in the reaction process, and corresponding group characteristic absorbance, carboxyl (1560cm appear in infrared analysis
-1And 1414cm
-1) and acyl aminocarbonyl (1640cm
-1) and do not have ester carbonyl group to absorb (1720cm
-1), carboxyl and acyl carboamidation displacement study (185 and 184ppm) appear in nmr analysis, prove that acylation reaction occurs over just 2 on the N atom.Anticoagulant active test proof, its activated partial thromboplastin time when 40 μ g/ml, thrombin time reaches 6 times and 2 times of corresponding sulfated chitosan respectively.
Embodiment 2
As embodiment 1, the Succinic anhydried consumption is 0.2g (sulfated chitosan sugar unit and a Succinic anhydried mol ratio 0.2), the ultimate analysis substitution value is 0.18mol/unit, anticoagulant active test proof, its activated partial thromboplastin time when 40 μ g/ml, thrombin time reaches 1.1 times and 2 times of corresponding sulfated chitosan respectively.
Embodiment 3
As embodiment 1, the Succinic anhydried consumption is 0.8g (sulfated chitosan sugar unit and a Succinic anhydried mol ratio 0.8), the ultimate analysis substitution value is 0.77mol/unit, anticoagulant active test proof, its activated partial thromboplastin time when 40 μ g/ml, thrombin time reaches 0.5 times and 0.9 times of corresponding sulfated chitosan respectively.
Embodiment 4
6-desulfurization acidic group sulfated chitosan 3.20g is dissolved in the 10ml methylsulfonic acid, places 0-5 ℃ of the molten maintenance of cryosel temperature, gradation adds Succinic anhydried 1.0g, stirs 30min and promptly places-5～0 ℃ of freezing 24～36h, and taking-up is thawed, dialysed 3 days, concentrate N, the carboxylated sulfated chitosan 1.2g of O-.The ultimate analysis substitution value is 0.58mol/unit, and gel chromatography proof molecular weight and sulfated chitosan difference are very little, do not have signs of degradation in the reaction process, and corresponding group characteristic absorbance, carboxyl (1560cm appear in infrared analysis
-1And 1414cm
-1) and acyl aminocarbonyl (1640cm
-1) and ester carbonyl group absorption (1720cm
-1), carboxyl and acyl carboamidation displacement study (185 and 184ppm) appear in nmr analysis, prove that acylation reaction had both occurred in 2 and has been the N atom, and also occurring in 3,6 is on the O atom.Anticoagulant active test proof, though shortage active group, still show faint anticoagulant active, its activated partial thromboplastin time when 40 μ g/ml, thrombin time reaches 1.5 times and 1.9 times of corresponding 6-desulfurization acidic group sulfated chitosan respectively.
Claims (9)
1. carboxylic butyryl radicals sulfated chitosan, its structural formula is:
R in the formula
1, R
2, R
3For-COCH
2CH
2COONa ,-SO
3Na or-H; Wherein-SO
3The substitution value of Na≤3 and greater than 0 ,-COCH
2CH
2The substitution value of COONa is 0.18-0.77; N is 15～50.
2. carboxylic butyryl radicals sulfated chitosan according to claim 1 is characterized in that: SO
3The Na substitution value is 1～2.
3. carboxylic butyryl radicals sulfated chitosan according to claim 1 and 2 is characterized in that: SO
3Na and CH
2CH
2OSO
3The substitution value sum of Na group is 1～2.
4. the method for making of the described carboxylic butyryl radicals of claim 1 sulfated chitosan; it is characterized in that: under the homogeneous phase condition; the sulfated chitosan of sulphur content 3～20wt%, molecular weight 5000～20000 is dissolved in the chitosan sulfate aqueous solution of ester that makes 5～30wt% in the distilled water; adding sulfated chitosan sugar unit and Succinic anhydried mol ratio and be 0.2～0.8 Succinic anhydried mixes; behind 20～30 ℃ of stirring reactions, promptly obtain carboxylic butyryl radicals sulfated chitosan through the dialysis lyophilize.
5. method for making according to claim 4 is characterized in that: sulfated chitosan substrate structure formula is
R in the formula
1, R
2, R
3For-COCH
2CH
2COONa ,-SO
3Na or-H; Wherein-SO
3The substitution value of Na≤3 and greater than 0 ,-COCH
2CH
2The substitution value of COONa is 0.18-0.77; N is 15～50.
6. method for making according to claim 5 is characterized in that: SO
3The Na substitution value is 1～2.
7. method for making according to claim 5 is characterized in that: SO
3Na and CH
2CH
2OSO
3The substitution value sum of Na group is 1～2.
8. according to claim 4 or 5 or 6 or 7 described method for makings, it is characterized in that: 25 ℃ of temperature of reaction, sulfated chitosan sulphur content 13.82wt%, the sulfated chitosan sugar unit is 0.6 with the mol ratio of positive Succinic anhydried, the concentration 20wt% of chitosan sulfate aqueous solution of ester.
9. the application of the described carboxylic butyryl radicals of claim 1 sulfated chitosan in the preparation anticoagulation medicine.
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|---|---|---|---|
| CN 200310111329 CN1252092C (en) | 2003-11-04 | 2003-11-04 | Carboxybutyryl chitosan sulfuric ester and preparation method and use thereof |
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|---|---|---|---|
| CN 200310111329 CN1252092C (en) | 2003-11-04 | 2003-11-04 | Carboxybutyryl chitosan sulfuric ester and preparation method and use thereof |
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| Publication Number | Publication Date |
|---|---|
| CN1542022A true CN1542022A (en) | 2004-11-03 |
| CN1252092C CN1252092C (en) | 2006-04-19 |
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|---|---|---|---|
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1294152C (en) * | 2005-03-02 | 2007-01-10 | 济南大学 | Hydrophobically modified succinylated chitosan derivative and its prepn process |
| CN100415807C (en) * | 2006-03-20 | 2008-09-03 | 扬州大学 | N-amber diacyl chitosan self-assembling nano particles and process for preparing same |
| CN101235100B (en) * | 2008-01-24 | 2013-03-20 | 青岛科技大学 | Method for cleanly preparing acylchitosan |
| CN103788230A (en) * | 2014-01-20 | 2014-05-14 | 浙江大学 | Method of modifying chitosan with cyclic anhydride and application of modified chitosan in ammonia absorption |
| CN109438708A (en) * | 2018-10-10 | 2019-03-08 | 大连理工大学 | A kind of preparation method of aliphatic poly monothioester |
-
2003
- 2003-11-04 CN CN 200310111329 patent/CN1252092C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1294152C (en) * | 2005-03-02 | 2007-01-10 | 济南大学 | Hydrophobically modified succinylated chitosan derivative and its prepn process |
| CN100415807C (en) * | 2006-03-20 | 2008-09-03 | 扬州大学 | N-amber diacyl chitosan self-assembling nano particles and process for preparing same |
| CN101235100B (en) * | 2008-01-24 | 2013-03-20 | 青岛科技大学 | Method for cleanly preparing acylchitosan |
| CN103788230A (en) * | 2014-01-20 | 2014-05-14 | 浙江大学 | Method of modifying chitosan with cyclic anhydride and application of modified chitosan in ammonia absorption |
| CN103788230B (en) * | 2014-01-20 | 2015-12-09 | 浙江大学 | With the method for cyclic acid anhydride beautify chitosan and the application in ammonia absorbs thereof |
| CN109438708A (en) * | 2018-10-10 | 2019-03-08 | 大连理工大学 | A kind of preparation method of aliphatic poly monothioester |
| CN109438708B (en) * | 2018-10-10 | 2020-11-03 | 大连理工大学 | Preparation method of aliphatic polythioester |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1252092C (en) | 2006-04-19 |
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