CN103418019B - Method of Zwitterionic modified oxidized regenerated cellulose absorbable hemostatic material and preparation - Google Patents
Method of Zwitterionic modified oxidized regenerated cellulose absorbable hemostatic material and preparation Download PDFInfo
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- 239000000463 material Substances 0.000 title claims abstract description 69
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims abstract description 13
- FSSPGSAQUIYDCN-UHFFFAOYSA-N 1,3-Propane sultone Chemical compound O=S1(=O)CCCO1 FSSPGSAQUIYDCN-UHFFFAOYSA-N 0.000 claims abstract description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 132
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 30
- 230000008569 process Effects 0.000 claims description 27
- 241001044369 Amphion Species 0.000 claims description 23
- 239000001361 adipic acid Substances 0.000 claims description 18
- 239000012948 isocyanate Substances 0.000 claims description 18
- 238000001291 vacuum drying Methods 0.000 claims description 15
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 claims description 11
- 239000012975 dibutyltin dilaurate Substances 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 10
- 230000003013 cytotoxicity Effects 0.000 abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 16
- 208000032843 Hemorrhage Diseases 0.000 description 12
- 230000000740 bleeding effect Effects 0.000 description 11
- 230000023597 hemostasis Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000000025 haemostatic effect Effects 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 229920002201 Oxidized cellulose Polymers 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229940107304 oxidized cellulose Drugs 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- UEEJHVSXFDXPFK-UHFFFAOYSA-O N-dimethylethanolamine Chemical compound C[NH+](C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-O 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- 229940030225 antihemorrhagics Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
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- 230000009286 beneficial effect Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
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- 238000007598 dipping method Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
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- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a preparation method of zwitterionic modified oxidized regenerated cellulose absorbable hemostatic material, and aims to solve the problems that the amount of carboxyl group is limited in the existing structure, thus hemostatic speed is low and cytotoxicity exists. The method includes 1, reacting with the 1, 6-adipate diisocyanate; 2, reacting with the N, N-dimethyl ethanolamine; and 3, reacting with the propane sultone. According to the zwitterionic modified oxidized regenerated cellulose absorbable hemostatic material, the zwitterionic structure is established on the surface of oxidized regenerated cellulose material, hemostatic performance of the material can be improved, cytotoxicity of the material can be optimized, and using effect of the material can be improved. The method is used for preparing the zwitterionic modified oxidized regenerated cellulose absorbable hemostatic material.
Description
Technical field
The present invention relates to the preparation method of modified oxidized regenerated cellulose hemostatic material.
Background technology
Inevitably there is various accident in daily life, carrying out in emergency treatment and operation process, all malpractice may be caused even dead because of massive hemorrhage.Therefore, the effective quick-acting haemostatic powder in patient local is then most important, and effective Bleeding control also reduces the important measures that the bleeding time becomes reduction mortality.Clinical conventional hemostatic material such as hemostatic gauze, stanch fibre, tourniquet bandage in use have limitation, as bleeding stopping period is longer, easily and wound adhesion and not easily changing dressings, to the infection of wound with suppurate helpless.The direction that quick-acting haemostatic powder and functional hemostasis will be the development of following haemostatic medicament.
Conventional Absorbable hemostatic material has Fibrin Glue, gelfoam, oxidized cellulose, microfibrillar collagen, chitosan and Sorbsan etc.Their mechanism of action and using method are not quite similar, and haemostatic effect also has difference.But the hemostatic gauze be widely used clinically is at present SURGICEL series absorbable hemostatic product---the SURGICEL produced by Johnson & Johnson of the U.S. (Johnson & Johnson) company
tM, SURGICEL
tMnu-Knit, SURGICEL
tMfibrillar, at home also known as " speed and yarn ", the composition of above product is oxidized regenerated cellulose, main difference is embodied in external expressive form, SURGICEL series of products have occupied extremely important status in the international market now, and receive the consistent favorable comment of medical domain expert.Meanwhile, domestic You Ji company has also produced similar hemostatic gauze, but can not show a candle to speed and yarn due to material property, adopts expensive import hemostatic material so main clinically.
Oxidized regenerated cellulose is cellulosic derivant, there are good anthemorrhagic performance, biodegradable performance and nontoxic, be used to multiple industry at present, comprise in the medical field, hydroxyl oxidize on C-6 position in cellulose unit, as oxidant, is that carboxyl obtains oxidized regenerated cellulose by general employing nitrogen oxide.When it uses as hemostatic material, carboxyl-content should be 16 ~ 24%, to ensure its haemostatic effect.Oxidized regenerated cellulose hemostatic mechanism is as follows: can adsorb a large amount of erythrocytes after oxidized regenerated cellulose contact blood, the acidic carboxypolymer then in oxidized regenerated cellulose structure can cause haemolysis, namely lyse red blood cells, break, and discharge hemoglobin.Meanwhile, due in hemoglobin containing ferric ion, oxidized regenerated cellulose can with Fe
3+in conjunction with the brown blob of viscose of formation, close, block blood capillary end and stop blooding.As can be seen here, the hemostasis of oxidized regenerated cellulose is a series of Biochemical Engineering, and the carboxyl limited amount in material structure, therefore causes the anthemorrhagic speed of oxidized regenerated cellulose material relatively slow.
In addition, bio-medical material, before entering Clinical practice, must pass through corresponding biological assessment, wherein most importantly Cytotoxic evaluation.Cell toxicity test is that a class is at ex vivo situation Imitating biology growing environment, the in vitro tests of test material and the reaction of device contacts body tissue artifact, it is one of most important Testing index in biological assessment system, is generally classified as first-selected and essential project.But the carboxyl playing anastalsis in regenerated oxycellulose as styptic material structure also causes the acidity of material comparatively strong, when carboxyl-content is between 16 ~ 24% time, the pH value of material is about 3.5.Obviously, acidity strong like this will certainly affect to the cell that material touches, and the homergy of interference cell, affects cell proliferation, even can make apoptosis.Further, due to the existence of carboxyl, make oxidized regenerated cellulose material surface be dispersed with a large amount of negative charges, when cell and material close to time, cell membrane modification, distortion can be made under the effect of negative charge, finally cause membranolysis.
In sum, the carboxyl in oxidized regenerated cellulose material structure is while playing anastalsis, and also make material be provided with certain cytotoxicity, such as, when carboxyl-content is between 16% ~ 24%, oxidized regenerated cellulose has 3 grades of cytotoxicities.Although such cytotoxicity is unlikely to cause material to use, but limit the use of material at some sensitive part of human body, as brain area.
For many years, many research workers are devoted to the study on the modification of regenerated oxycellulose as styptic material always.The people such as Doub disclose the method adopting the aqueous solution of sodium bicarbonate or calcium acetate to neutralize oxidized regenerated cellulose, and with the oxidized regenerated cellulose of thrombin dipping sodium bicarbonate neutralization, then process is freezed to the fabric after dipping and drying in this case, obtained a kind of efficient oxidized cellulose class surgical operation hemostatic material.In United States Patent (USP), the people such as Saferstein describes the alcohol-water solution using salt of weak acid, as calcium acetate, oxidized regenerated cellulose is neutralized to pH value between 5 ~ 8, this method not only makes oxidized regenerated cellulose store by ambient-temp-stable, and can the acid-sensitive material of similar thrombin in load, and then improve the anthemorrhagic performance of oxidized regenerated cellulose material.During in another part of United States Patent (USP), the people such as Stilwell then adopts and method prepared a kind of regenerated oxycellulose as styptic material of calcium modification of good results, they find when the calcium content in oxidized cellulose is between 0.4 ~ 5.0, the anthemorrhagic performance of the oxidized cellulose of calcium modification is better than the oxidized regenerated cellulose of unmodified oxidized regenerated cellulose and sodium or potassium modification, and is not too large on the Bioabsorbable impact of material.When adopting calcium and sodium or potassium mixed and modified, the calcium contained in the modified oxidized regenerated cellulose of gained can realize strengthening haemostatic effect.
Although above achievement in research all has a very big significance the correlational study of oxidized regenerated cellulose, but only concentrate on the hemostasis usefulness angle improving oxidized regenerated cellulose material, and the rare report of improvement research to oxidized regenerated cellulose Materials Cell toxicity aspect.Therefore, propose a kind of anthemorrhagic performance that can improve oxidized regenerated cellulose material, the Cytotoxic method of modifying simultaneously contributing to again improving material is significant.
Summary of the invention
The present invention will solve the carboxyl limited amount in current material structure, causes anthemorrhagic speed relatively slow, there is Cytotoxic problem simultaneously, and the preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of the amphion provided.
The modified oxidized regenerated cellulose Absorbable hemostatic material of amphion is by oxidized regenerated cellulose, 1,6-adipic acid isocyanates, N, N-dimethylethanolamine, propane sultone, dibutyl tin dilaurate and toluene are prepared from, and wherein in oxidized regenerated cellulose, carboxyl-content is 16% ~ 24%.
The preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion, specifically carry out according to following steps:
One, by 1,6-adipic acid isocyanates and first group of toluene mix homogeneously, control mixing speed is 100r/min, then add dibutyl tin dilaurate, being heated to temperature is 30 DEG C ~ 85 DEG C, then adds oxidized regenerated cellulose, keep 0.5h ~ 4h, then put into successively toluene and acetone cleaning 2 ~ 5 times, then by process after oxidized regenerated cellulose vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C; Wherein, the mass ratio of 1,6-adipic acid isocyanates and oxidized regenerated cellulose is 0.1 ~ 18;
Two, by N, N-dimethylethanolamine and second group of toluene mix homogeneously, control mixing speed is 100r/min, then the oxidized regenerated cellulose that step one processes is put into, keep 10h ~ 40h, again by process after oxidized regenerated cellulose put into successively toluene and acetone cleaning 2 ~ 6 times, then vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C;
Three, by propane sultone and the 3rd group of toluene mix homogeneously, control mixing speed is 100r/min, being warming up to temperature is 20 DEG C ~ 80 DEG C, add the oxidized regenerated cellulose of step 2 process again, keep 8h ~ 48h, then the oxidized regenerated cellulose after process is cleaned 2 ~ 6 times respectively with toluene, deionized water and acetone successively, then vacuum drying 16h ~ 72h, controlling baking temperature is-80 DEG C ~-10 DEG C, obtains the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion;
The mass ratio of above-mentioned 1,6-adipic acid isocyanates and N, N-dimethylethanolamine is 2 ﹕ (1 ~ 5), and the mass ratio of N, N-dimethylethanolamine and propane sultone is 10 ﹕ (14 ~ 15);
In step one, the mass ratio of 1,6-adipic acid isocyanates and dibutyl tin dilaurate is (20 ~ 400) ﹕ 1;
The volume ratio of first group of toluene, second group of toluene and the 3rd group of toluene is that in the volume of 1 ﹕ 1 ﹕, 1, first group of toluene and step one, the mass ratio of oxidized regenerated cellulose is 20mL ﹕ 0.5g.
The invention has the beneficial effects as follows: the present invention builds amphion structure at oxidized regenerated cellulose material surface, the anthemorrhagic performance of material can be improved, contribute to again the cytotoxicity improving material simultaneously, and then improve the effective utilization of material, expand the range of application of material.
The mass fraction of the amphion composition of amphion prepared by the present invention modified oxidized regenerated cellulose Absorbable hemostatic material surface construction is 10% ~ 60%.
The present invention is for the preparation of the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion.
Detailed description of the invention
Technical solution of the present invention is not limited to following cited detailed description of the invention, also comprises the combination in any between each detailed description of the invention.
Detailed description of the invention one: the modified oxidized regenerated cellulose Absorbable hemostatic material of present embodiment amphion is by oxidized regenerated cellulose, 1,6-adipic acid isocyanates, N, N-dimethylethanolamine, propane sultone, dibutyl tin dilaurate and toluene are prepared from, and wherein in oxidized regenerated cellulose, carboxyl-content is 16% ~ 24%.
Detailed description of the invention two: present embodiment and detailed description of the invention one unlike: the appearance forrns of described oxidized regenerated cellulose is short silk, long filament or fabric.Other is identical with detailed description of the invention one.
Detailed description of the invention three: present embodiment and detailed description of the invention one unlike: 1,6-adipic acid isocyanates and N, the mass ratio of N-dimethylethanolamine is 2 ﹕ (1 ~ 5), and the mass ratio of N, N-dimethylethanolamine and propane sultone is 10 ﹕ (14 ~ 15).Other is identical with detailed description of the invention one.
Detailed description of the invention four: present embodiment and detailed description of the invention one unlike: the mass ratio of 1,6-adipic acid isocyanates and dibutyl tin dilaurate is (20 ~ 400) ﹕ 1.Other is identical with detailed description of the invention one.
Detailed description of the invention five: the preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of the amphion described in detailed description of the invention one, specifically carry out according to following steps:
One, by 1,6-adipic acid isocyanates and first group of toluene mix homogeneously, control mixing speed is 100r/min, then add dibutyl tin dilaurate, being heated to temperature is 30 DEG C ~ 85 DEG C, then adds oxidized regenerated cellulose, keep 0.5h ~ 4h, then put into successively toluene and acetone cleaning 2 ~ 5 times, then by process after oxidized regenerated cellulose vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C; Wherein, the mass ratio of 1,6-adipic acid isocyanates and oxidized regenerated cellulose is 0.1 ~ 18;
Two, by N, N-dimethylethanolamine and second group of toluene mix homogeneously, control mixing speed is 100r/min, then the oxidized regenerated cellulose that step one processes is put into, keep 10h ~ 40h, again by process after oxidized regenerated cellulose put into successively toluene and acetone cleaning 2 ~ 6 times, then vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C;
Three, by propane sultone and the 3rd group of toluene mix homogeneously, control mixing speed is 100r/min, being warming up to temperature is 20 DEG C ~ 80 DEG C, add the oxidized regenerated cellulose of step 2 process again, keep 8h ~ 48h, then the oxidized regenerated cellulose after process is cleaned 2 ~ 6 times respectively with toluene, deionized water and acetone successively, then vacuum drying 16h ~ 72h, controlling baking temperature is-80 DEG C ~-10 DEG C, obtains the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion;
The mass ratio of above-mentioned 1,6-adipic acid isocyanates and N, N-dimethylethanolamine is 2 ﹕ (1 ~ 5), and the mass ratio of N, N-dimethylethanolamine and propane sultone is 10 ﹕ (14 ~ 15);
In step one, the mass ratio of 1,6-adipic acid isocyanates and dibutyl tin dilaurate is (20 ~ 400) ﹕ 1;
The volume ratio of first group of toluene, second group of toluene and the 3rd group of toluene is that in the volume of 1 ﹕ 1 ﹕, 1, first group of toluene and step one, the mass ratio of oxidized regenerated cellulose is 20mL ﹕ 0.5g.
Following examples are adopted to verify beneficial effect of the present invention:
Embodiment one:
The preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of the present embodiment amphion, specifically carry out according to following steps:
One, by 2g1,6-adipic acid isocyanates and 20mL first group of toluene mix homogeneously, control mixing speed is 100r/min, then add 0.010g dibutyl tin dilaurate, being heated to temperature is 50 DEG C, then adds 0.5g oxidized regenerated cellulose, keep 1.5h, then put into successively toluene and acetone cleaning 3 times, then by process after oxidized regenerated cellulose vacuum drying 16h, control baking temperature be-10 DEG C;
Two, by 2gN, N-dimethylethanolamine and 20mL second group of toluene mix homogeneously, control mixing speed is 100r/min, then the oxidized regenerated cellulose that step one processes is put into, keep 24h, again by process after oxidized regenerated cellulose put into successively toluene and acetone cleaning 3 times, then vacuum drying 16h, control baking temperature be-20 DEG C;
Three, by 2g propane sultone and 20mL the 3rd group of toluene mix homogeneously, control mixing speed is 100r/min, being warming up to temperature is 50 DEG C, add the oxidized regenerated cellulose of step 2 process again, keep 24h, then the oxidized regenerated cellulose after process is cleaned 3 times respectively with toluene, deionized water and acetone successively, then vacuum drying 16h, control baking temperature and be-10 DEG C, obtain the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion.
In the present embodiment, the appearance forrns of oxidized regenerated cellulose is fabric.
In the present embodiment, the carboxyl-content of unmodified oxidized regenerated cellulose is 18.41%, and the mass fraction obtaining the amphion composition of amphion modified oxidized regenerated cellulose Absorbable hemostatic material surface construction is 12.06%.
Carry out cytotoxicity test according to ISO10993 standard, modified oxidized regenerated cellulose has 0 grade of cytotoxicity, i.e. material no cytotoxicity.Unmodified oxidized regenerated cellulose material there are 3 grades of cytotoxicities.
Bleeding stopping period measures: after slowly injecting Nembutal sodium solution anesthetized animal by 40mg/kg dose intravenous, by its central arteria auricularis region preserved skin, sterilization, skin is cut along arteria auricularis direction, blunt separation goes out arteria auricularis, vein and nerve, use scalpel transversely cutting tremulous pulse again, stick in wound surface with 1 layer of test material or control sample immediately after blood is gushed out and use pull and push dynamometer to apply the pressure of 3N, observing hemostasis every 10s, until record bleeding stopping period after final hemostasis completely.Test result is as follows: the bleeding stopping period of unmodified oxidized regenerated cellulose (carboxyl-content 18.41%) is 118s, and the bleeding stopping period of modified oxidized regenerated cellulose is 106s.
Embodiment two:
The preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of the present embodiment amphion, specifically carry out according to following steps:
One, by 8g1,6-adipic acid isocyanates and 20mL first group of toluene mix homogeneously, control mixing speed is 100r/min, then add 0.100g dibutyl tin dilaurate, being heated to temperature is 50 DEG C, then adds 0.5g oxidized regenerated cellulose, keep 2h, then put into toluene and acetone cleaning 3 times, then by process after oxidized regenerated cellulose vacuum drying 16h, control baking temperature be-10 DEG C;
Two, by 12.5gN, N-dimethylethanolamine and 20mL second group of toluene mix homogeneously, control mixing speed is 100r/min, then the oxidized regenerated cellulose that step one processes is put into successively, keep 30h, again by process after oxidized regenerated cellulose put into successively toluene and acetone cleaning 3 times, then vacuum drying 16h, control baking temperature be-10 DEG C;
Three, by 15g propane sultone and 20mL the 3rd group of toluene mix homogeneously, control mixing speed is 100r/min, being warming up to temperature is 50 DEG C, add the oxidized regenerated cellulose of step 2 process again, keep 48h, then the oxidized regenerated cellulose after process is cleaned 3 times respectively with toluene, deionized water and acetone successively, then vacuum drying 72h, control baking temperature and be-10 DEG C, obtain the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion.
In the present embodiment, the appearance forrns of oxidized regenerated cellulose is fabric.
In the present embodiment, the carboxyl-content of unmodified oxidized regenerated cellulose is 18.41%, and the mass fraction obtaining the amphion composition of amphion modified oxidized regenerated cellulose Absorbable hemostatic material surface construction is 46.37%.
Carry out cytotoxicity test according to ISO 10993 standard, modified oxidized regenerated cellulose has 0 grade of cytotoxicity, i.e. material no cytotoxicity.Unmodified oxidized regenerated cellulose material there are 3 grades of cytotoxicities.
Bleeding stopping period measures: after slowly injecting Nembutal sodium solution anesthetized animal by 40mg/kg dose intravenous, by its central arteria auricularis region preserved skin, sterilization, skin is cut along arteria auricularis direction, blunt separation goes out arteria auricularis, vein and nerve, use scalpel transversely cutting tremulous pulse again, stick in wound surface with 1 layer of test material or control sample immediately after blood is gushed out and use pull and push dynamometer to apply the pressure of 3N, observing hemostasis every 10s, until record bleeding stopping period after final hemostasis completely.Test result is as follows: the bleeding stopping period of unmodified oxidized regenerated cellulose (carboxyl-content 18.41%) is 118s, and the bleeding stopping period of modified oxidized regenerated cellulose material is 92s.
Claims (1)
1. the preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion, is characterized in that the preparation method of the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion, specifically carries out according to following steps:
One, by 1,6-adipic acid isocyanates and first group of toluene mix homogeneously, control mixing speed is 100r/min, then add dibutyl tin dilaurate, being heated to temperature is 30 DEG C ~ 85 DEG C, then adds oxidized regenerated cellulose, keep 0.5h ~ 4h, then put into successively toluene and acetone cleaning 2 ~ 5 times, then by process after oxidized regenerated cellulose vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C; Wherein, the mass ratio of 1,6-adipic acid isocyanates and oxidized regenerated cellulose is 0.1 ~ 18;
Two, by N, N-dimethylethanolamine and second group of toluene mix homogeneously, control mixing speed is 100r/min, then the oxidized regenerated cellulose that step one processes is put into, keep 10h ~ 40h, again by process after oxidized regenerated cellulose put into successively toluene and acetone cleaning 2 ~ 6 times, then vacuum drying 16h ~ 72h, control baking temperature be-80 DEG C ~-10 DEG C;
Three, by propane sultone and the 3rd group of toluene mix homogeneously, control mixing speed is 100r/min, being warming up to temperature is 20 DEG C ~ 80 DEG C, add the oxidized regenerated cellulose of step 2 process again, keep 8h ~ 48h, then the oxidized regenerated cellulose after process is cleaned 2 ~ 6 times respectively with toluene, deionized water and acetone successively, then vacuum drying 16h ~ 72h, controlling baking temperature is-80 DEG C ~-10 DEG C, obtains the modified oxidized regenerated cellulose Absorbable hemostatic material of amphion;
The mass ratio of above-mentioned 1,6-adipic acid isocyanates and N, N-dimethylethanolamine is 2 ﹕ (1 ~ 5), and the mass ratio of N, N-dimethylethanolamine and propane sultone is 10 ﹕ (14 ~ 15);
In step one, the mass ratio of 1,6-adipic acid isocyanates and dibutyl tin dilaurate is (20 ~ 400) ﹕ 1;
The volume ratio of first group of toluene, second group of toluene and the 3rd group of toluene is that in the volume of 1 ﹕ 1 ﹕, 1, first group of toluene and step one, the mass ratio of oxidized regenerated cellulose is 20mL ﹕ 0.5g;
In oxidized regenerated cellulose described in step one, carboxyl-content is 16% ~ 24%;
The appearance forrns of oxidized regenerated cellulose described in step one is short silk, long filament or fabric.
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| CN104383584B (en) * | 2014-11-21 | 2016-10-05 | 哈尔滨工业大学 | A kind of Graphene/oxidized regenerated cellulose compound hemostatic material |
| CN104383578B (en) * | 2014-12-01 | 2016-05-11 | 哈尔滨工业大学 | A kind of graphene oxide graft modification regenerated oxycellulose as styptic material and preparation method thereof |
| CN104383587B (en) * | 2014-12-01 | 2016-10-19 | 哈尔滨工业大学 | A kind of fullerene/oxidized regenerated cellulose compound hemostatic material and preparation method thereof |
| CN104383577B (en) * | 2014-12-01 | 2016-10-05 | 哈尔滨工业大学 | A kind of nanometer gold/oxidized regenerated cellulose compound hemostatic material |
| CN106554423B (en) * | 2016-11-29 | 2019-02-12 | 东北林业大学 | A kind of amphoteric ion cellulose material and preparation method thereof |
| CN110464869B (en) * | 2019-07-29 | 2021-11-19 | 亳州市新健康科技有限公司 | Preparation method and application of self-thickening bone wound hemostasis gel |
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