CN101632685B - 含有羧基的醛改性多糖在制备药物和医用材料中的应用 - Google Patents
含有羧基的醛改性多糖在制备药物和医用材料中的应用 Download PDFInfo
- Publication number
- CN101632685B CN101632685B CN2009100179379A CN200910017937A CN101632685B CN 101632685 B CN101632685 B CN 101632685B CN 2009100179379 A CN2009100179379 A CN 2009100179379A CN 200910017937 A CN200910017937 A CN 200910017937A CN 101632685 B CN101632685 B CN 101632685B
- Authority
- CN
- China
- Prior art keywords
- aldehyde
- modified polysaccharide
- carboxyl
- polysaccharide
- molecule
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000012567 medical material Substances 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 150000004676 glycans Chemical class 0.000 title abstract description 64
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 title abstract description 60
- 229920001282 polysaccharide Polymers 0.000 title abstract description 60
- 239000005017 polysaccharide Substances 0.000 title abstract description 60
- 230000004048 modification Effects 0.000 claims description 20
- 238000012986 modification Methods 0.000 claims description 20
- 229920001661 Chitosan Polymers 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 10
- 230000023597 hemostasis Effects 0.000 claims description 5
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 2
- 159000000000 sodium salts Chemical class 0.000 claims 2
- 206010052428 Wound Diseases 0.000 abstract description 12
- 208000027418 Wounds and injury Diseases 0.000 abstract description 12
- 230000001965 increasing effect Effects 0.000 abstract description 10
- 239000000463 material Substances 0.000 abstract description 9
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 241000894006 Bacteria Species 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 208000031737 Tissue Adhesions Diseases 0.000 abstract description 4
- 125000003172 aldehyde group Chemical group 0.000 abstract description 4
- 239000003937 drug carrier Substances 0.000 abstract description 4
- 230000012010 growth Effects 0.000 abstract description 4
- 210000004881 tumor cell Anatomy 0.000 abstract description 4
- 230000035876 healing Effects 0.000 abstract description 3
- 230000009257 reactivity Effects 0.000 abstract description 3
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 238000010521 absorption reaction Methods 0.000 abstract description 2
- 230000004614 tumor growth Effects 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract 2
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- -1 aldehyde radical Chemical class 0.000 description 24
- 229940045110 chitosan Drugs 0.000 description 16
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 11
- 239000000661 sodium alginate Substances 0.000 description 11
- 235000010413 sodium alginate Nutrition 0.000 description 11
- 229940005550 sodium alginate Drugs 0.000 description 11
- 229920002678 cellulose Polymers 0.000 description 10
- 239000001913 cellulose Substances 0.000 description 10
- 235000010980 cellulose Nutrition 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 229920002201 Oxidized cellulose Polymers 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 229940107304 oxidized cellulose Drugs 0.000 description 9
- 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 8
- 235000015097 nutrients Nutrition 0.000 description 8
- 229920002101 Chitin Polymers 0.000 description 7
- 239000004744 fabric Substances 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 229920000742 Cotton Polymers 0.000 description 5
- 239000006916 nutrient agar Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000012531 culture fluid Substances 0.000 description 4
- 210000003701 histiocyte Anatomy 0.000 description 4
- 150000004804 polysaccharides Polymers 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000004627 regenerated cellulose Substances 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000000025 haemostatic effect Effects 0.000 description 3
- 230000002439 hemostatic effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920001503 Glucan Polymers 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010061323 Optic neuropathy Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940027278 hetastarch Drugs 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 239000001341 hydroxy propyl starch Substances 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229940054190 hydroxypropyl chitosan Drugs 0.000 description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000020911 optic nerve disease Diseases 0.000 description 2
- 210000004279 orbit Anatomy 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- 108700005239 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Proteins 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 101100515516 Arabidopsis thaliana XI-H gene Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- SJRXVLUZMMDCNG-UHFFFAOYSA-N Gossypin Natural products OC1C(O)C(O)C(CO)OC1OC1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=C(O)C2=O SJRXVLUZMMDCNG-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000005030 aluminium foil Substances 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002364 anti-haemorrhagic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- SJRXVLUZMMDCNG-KKPQBLLMSA-N gossypin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=C(O)C2=O SJRXVLUZMMDCNG-KKPQBLLMSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
一种含有羧基的醛改性多糖在制备止血、愈创、抑菌、抗肿瘤、组织粘合或创面封闭的药物和医用材料中的应用;所述的含有羧基的醛改性多糖分子中含有醛基和羧基盐。本发明的含有羧基的醛改性多糖由于分子中含有醛基,增加了多糖的反应活性,能抑制细菌生长,抑制肿瘤细胞生长,具有止血作用、组织细胞粘合作用和创面封闭的作用,能作为药物载体材料,醛基也同时增加了醛改性多糖的生物降解性;分子中的羧基盐增加了醛改性多糖的亲水性和生物相容性,在人体内降解吸收时不会形成局部酸性,能增加人体的生物相容性,使得醛改性多糖适用于人体体表、人体体内。
Description
技术领域
本发明涉及一种醛改性多糖,特别是涉及一种含有羧基的醛改性多糖在制备药物和医用材料中的应用。
背景技术
多糖由于具有无免疫原性、可生物降解、生物安全性好等优点,在生物与医药技术领域的应用已有较多的报道。例如,淀粉、纤维素作为药物辅料,纤维素制备医用纱布、脱脂棉,壳聚糖、壳聚糖衍生物制备组织工程支架材料等。但多糖的种类不同,其水溶解性不同,生物降解性不同,生物学功能也不同。目前已有很多有关多糖修饰改性的报道,如将壳聚糖改性为水溶性的羧甲基壳聚糖,增加其水溶性,纤维素氧化成为羧酸纤维素,增加其生物降解性。
纤维素经不同形式的氧化反应可生成含有醛基(-CHO)、羧基(-COOH)或酮基的多糖(武利顺等,纤维素的选择性氧化反应及其体系,人造纤维,30(3):27-31,2000年)。纤维素的羟基可氧化成醛基,也可继续氧化成羧基。常规的氧化纤维素和氧化再生纤维素均含有羧基(-COOH)。美国Johnson&Johnson公司的医用可吸收止血纱布Surgicel是纤维素经氧化后制成的止血材料,有氧化纤维素和氧化还原纤维素两种产品,常见的氧化纤维素产品是从棉纤维素处理得到的白色或乳白色的针织物、机织物、絮片、海绵状物,其主要技术指标之一是干态下氧化纤维素中羧基(-COOH)含量为16%~24%,以保证其止血效果(孙宾等,医用可吸收氧化纤维素及其氧化体系研究进展,中国纺织大学学报,26(4):110-114,2000年)。然而,氧化纤维素和氧化再生纤维素由于其羧基可形成局部酸性,能引起包括凝血酶或纤维蛋白原等酸性敏感止血物质的快速变性(CN 1502374A)。同时也有报道显示,在眼眶手术中使用氧化再生纤维素后,出现眶压增高性视神经病变(Arat Y.O.等,眼眶手术中使用氧化再生纤维素后并发眶压增高性视神经病变的并发症、预防及治疗的回顾性研究,世界核心医学期刊文摘:眼科学分册,2(6):56-57,2006年)。Nagamatsu实验结果也提示氧化纤维素的酸性可能引起神经纤维变性,因此应避免对外围神经直接使用大量氧化纤维素(Masaaki Nagamatsu,JewelPodratz,Anthony J.Windebank,et al。Acidity is involved in the development ofneuropathy caused by oxidized cellulose,Journal of the Neurological Sciences,146(2):97-102,1997)。公开号为CN 1502375A、CN 1509768A、CN 1502376A的发明专利均公开了一种醛改性多糖的伤口敷料,该三个专利的一个共同技术特征是该伤口敷料含有醛改性多糖,该醛改性多糖不含有羧基(-COOH)。然而,有报道显示,随着多糖中醛基含量的增加,醛改性多糖的吸水率明显下降,疏水性有明显的提高(张水洞等,用于制备热塑性塑料的双醛玉米淀粉的研究,四川大学学报:自然科学版,44(3):649-652,2007年)。因此,仅含有醛基的醛改性多糖在医用材料中应用仍有不足。
发明内容
本发明的目的是提供一种含有羧基的醛改性多糖在制备药物和医用材料中的应用,以弥补现有技术的上述不足。
一种含有羧基的醛改性多糖在制备止血、愈创、抑菌、抗肿瘤、组织粘合或创面封闭的药物和医用材料中的应用;所述的含有羧基的醛改性多糖分子中含有醛基和羧基盐。
本发明的含有羧基的醛改性多糖由于分子中含有醛基,增加了多糖分子的反应活性,能抑制细菌生长,抑制肿瘤细胞生长,具有止血作用、组织细胞粘合作用和创面封闭的作用,能作为药物载体材料,醛基也同时增加了醛改性多糖的生物降解性;分子中的羧基盐增加了醛改性多糖的亲水性和生物相容性,在人体内降解吸收时不会形成局部酸性,能增加人体的生物相容性,使得醛改性多糖适用于人体体表、人体体内。
具体实施方式
以下通过实施例对本发明作进一步说明:
实施例1含有羧基的醛改性多糖的制备及其在止血、愈创中的应用:
在体积为1000ml的2%(重量百分浓度,下同)的海藻酸钠水溶液中,按海藻酸钠与高碘酸钠的摩尔比为2∶1的比例加入5%的高碘酸钠水溶液,室温避光搅拌反应24小时,加入5ml乙二醇终止氧化反应0.5小时,用乙醇沉淀反应产物,抽滤,用无水乙醇脱水,抽滤得白色固形物,常温下真空干燥,制得含有羧基的醛改性海藻酸钠,该含有羧基的醛改性海藻酸钠分子中的醛基与海藻酸钠中糖残基的摩尔比为0.7∶1,羧酸钠与海藻酸钠糖残基的摩尔比为1∶1。将干燥后的含有羧基的醛改性海藻酸钠用铝箔袋包装,经60Co辐照灭菌,得无菌的含有羧基的醛改性多糖。
在本发明中,所述的含有羧基的醛改性多糖还可由纤维素、羧甲基纤维素、羟乙基纤维素、羟丙基纤维素、淀粉、羧甲基淀粉、羟乙基淀粉、羟丙基淀粉、葡聚糖、羧甲基葡聚糖、甲壳素、羧甲基甲壳素、羟乙基甲壳素、羟丙基甲壳素、壳聚糖、羧甲基壳聚糖、羟乙基壳聚糖、羟丙基壳聚糖、琥珀酰壳聚糖和透明质酸经氧化改性而制成。这些含有羧基的醛改性多糖分子中的醛基与多糖残基的摩尔比为(0.05~1)∶1,羧酸基盐与多糖残基的摩尔比为(0.1~1)∶1。
采用Wistar大白鼠作为试验动物,大白鼠27只,均为雄性,体重250g±20g。试验分3组:棉纱布对照组、含有羧基的醛改性海藻酸钠组、含有羧基的醛改性羧甲基壳聚糖钠组,每组9只。分别以30mg/Kg体重腹腔注射2%的戊巴比妥钠麻醉,将大白鼠背部朝上固定在手术架上,用剃须刀片将背部剃去1cm×2cm面积的毛发,并用新洁尔灭棉球进行皮肤消毒。用消毒的刀片在背部去毛部位做1.5cm长、2mm深的切口,有血流出。各试验组进行下列处理:(1)棉纱布对照组大鼠切口暴露;(2)含有羧基的醛改性海藻酸钠组在大鼠切口处均匀敷0.5g上述无菌的含有羧基的醛改性海藻酸钠粉盖住切口;(3)含有羧基的醛改性羧甲基壳聚糖钠组在大鼠切口处均匀滴加0.5ml 2%的含有羧基的醛改性羧甲基壳聚糖钠(另行制备的,并已经过60Co辐照灭菌)水溶液。手术中观察每只大鼠创面出血情况,记录止血时间,以评价含有羧基的醛改性多糖对手术刀口的止血效果。术后各组大鼠均用无菌纱布包扎,正常饲养,每天观察大鼠刀口愈合情况,以评价含有羧基的醛改性多糖对大鼠伤口愈合的影响。结果列于下表:
以上试验结果证明,含有羧基的醛改性海藻酸钠和含有羧基的醛改性羧甲基壳聚糖钠的止血效果和促进伤口愈合效果明显优于棉纱布,因此含有羧基的醛改性多糖作为一种新型止血、愈创材料进行开发,前景广阔,可在制备止血、愈创的药物或医用材料中应用。
实施例2含有羧基的醛改性多糖在抑菌中的应用:
(1)按《中华人民共和国药典》2005年版二部(国家药典委员会编)附录XI H无菌检查法项下的培养基的制备(附录89-附录90)中所述的方法,按比例配制营养琼脂培养基200ml置于带棉塞的500ml三角瓶中。再按该方法,不加琼脂,其它成分均按比例加入,配制营养液体培养基50ml,置于带棉塞的250ml三角瓶中,标记为1#瓶;不加琼脂,加入0.5g含有羧基的醛改性海藻酸钠,其它成分均按比例加入,配制含有羧基的醛改性多糖营养液体培养基50ml,置于另一带棉塞的250ml三角瓶中,标记为2#瓶。全部培养基均于121℃下压力蒸汽灭菌25分钟,得无菌营养琼脂培养基、无菌营养液体培养基和无菌含羧基的醛改性多糖营养液体培养基。
(2)将无菌营养琼脂培养基加热至溶化,倒6个平板,冷却至凝固,得营养琼脂平板。
(3)取大肠杆菌斜面1支,无菌条件下分别用接种环各接取1环大肠杆菌于装有无菌营养液体培养基的1#瓶,和装有无菌的含有羧基的改性多糖营养液体培养基的2#瓶中,盖上棉塞,分别标记为1#培养液和2#培养液。全部培养液均置35℃恒温培养箱中培养2h。2h后,分别从1#、2#培养液中各取0.2ml,分别涂布3个营养琼脂平板,共6个平板,并对应地将涂布的平板标记为1#-1、1#-2、1#-3、2#-1、2#-2、2#-3,全部平板置35℃恒温培养箱中培养48h后,观察各平板上大肠杆菌的生长情况。
(4)实验结果见下表。
实验结果表明,添加含有羧基的醛改性多糖的营养液体培养基与不添加含有羧基的醛改性多糖营养液体培养基相比,前者对大肠杆菌生长显示出抑制作用,表现为菌落数量的减少和菌落直径变小,说明含有羧基的醛改性多糖具有抑制细菌生长的作用。因此本发明的含有羧基的醛改性多糖作为一种抑菌的药物或医用材料进行开发,前景广阔,可在制备抑菌的药物或医用材料中应用。
在实施例1和实施例2中,所述的含有羧基的醛改性多糖是分子中含有醛基和羧基盐的任意一种醛改性多糖,或者是在多糖分子经氧化反应引入了醛基和羧基盐,或者是本身带有羧基盐的多糖经氧化形成醛基,如含有羧基的醛改性的羧甲基淀粉钠,含有羧基的醛改性羧甲基壳聚糖钾,含有羧基的醛改性的氧化纤维素钠,含有羧基的醛改性海藻酸钠,含有羧基的醛改性透明质酸钠。因此,所述的含有羧基的醛改性多糖可以是由纤维素、羧甲基纤维素、羟乙基纤维素、羟丙基纤维素、淀粉、羧甲基淀粉、羟乙基淀粉、羟丙基淀粉、葡聚糖、羧甲基葡聚糖、甲壳素、羧甲基甲壳素、羟乙基甲壳素、羟丙基甲壳素、壳聚糖、羧甲基壳聚糖、羟乙基壳聚糖、羟丙基壳聚糖、琥珀酰壳聚糖、透明质酸或海藻酸盐经改性而制成的含有醛基和羧基盐的醛改性多糖中的一种;所述的含有羧基的醛改性多糖的分子中含有醛基和羧基盐,分子中的醛基与多糖残基的摩尔比为(0.05~1)∶1,羧基盐与多糖残基的摩尔比为(0.1~1)∶1;所述的羧基盐为羧酸钠或羧酸钾。
所述的含有羧基的醛改性多糖由于其分子结构中含有醛基和羧基盐,分子中的醛基增加了多糖分子的反应活性,能与蛋白质、氨基酸、核酸、核苷酸等含有氨基的物质发生反应,从而使得所述的改性多糖医用材料具有多种生物功能,能与细菌细胞结合,抑制细菌生长,能在制备具有抑菌作用的药物和医用材料中应用;能与肿瘤细胞结合,抑制肿瘤细胞生长,能在制备具有肿瘤抑制作用的药物和医用材料中应用;能与血红细胞结合,引起红细胞聚集,具有止血作用,能在制备具有止血作用的药物和医用材料中应用;能与机体组织细胞结合,具有组织细胞粘合的作用,能在制备组织粘合和创面封闭的药物和医用材料中应用;能够与带有氨基的物质结合,能在制备药物载体材料的医用材料中应用;分子中的醛基也同时增加了多糖的生物降解性,易于在机体内被降解吸收。所述的含有羧基的醛改性多糖分子中的羧基盐增加了醛改性多糖的亲水性和生物相容性,在人体内降解吸收时不会形成局部酸性,不引起机体内的酸性敏感物质的变性,不引起机体组织、机体细胞的炎症反应,增加了人体的生物相容性,使得所述的含有羧基的醛改性多糖适用于人体体表、人体体内。因此所述的含有羧基的醛改性多糖的任意一种均能达到上述功能效果。
所述的含有羧基的醛改性多糖可以制成不同物理形态的药物或医用材料,如非织布、针织布、编织布、机织布、纤维、棉条、海绵、泡沫、膜、粉、颗粒、珠状物、胶体或溶液,用于抑制细菌生长、抑制肿瘤生长、止血愈创、药物载体、组织细胞、组织细胞支架、创面封闭。
Claims (1)
1.一种醛改性的羧甲基壳聚糖钠盐或钾盐在制备止血、愈创的药物和医用材料中的应用;所述的醛改性的羧甲基壳聚糖钠盐或钾盐分子中含有醛基。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100179379A CN101632685B (zh) | 2009-08-05 | 2009-08-05 | 含有羧基的醛改性多糖在制备药物和医用材料中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100179379A CN101632685B (zh) | 2009-08-05 | 2009-08-05 | 含有羧基的醛改性多糖在制备药物和医用材料中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101632685A CN101632685A (zh) | 2010-01-27 |
CN101632685B true CN101632685B (zh) | 2012-07-04 |
Family
ID=41592124
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2009100179379A Expired - Fee Related CN101632685B (zh) | 2009-08-05 | 2009-08-05 | 含有羧基的醛改性多糖在制备药物和医用材料中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101632685B (zh) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103055343B (zh) * | 2011-10-19 | 2014-07-30 | 袁暾 | 一种马铃薯淀粉-透明质酸复合止血粉及其制备方法 |
CN102488918A (zh) * | 2011-12-01 | 2012-06-13 | 中国人民解放军第四军医大学 | 壳聚糖在负压或封闭环境下作为治疗创面药物的用途 |
CN104606222B (zh) * | 2015-01-13 | 2017-09-05 | 河北柯瑞生物医药有限公司 | 一种植物多糖清洗液 |
CN105327388B (zh) * | 2015-12-07 | 2018-10-26 | 莫秀梅 | 一种医用粘合剂及其制备方法 |
CN107137752B (zh) * | 2016-03-01 | 2020-06-19 | 南京理工大学 | 一种丝瓜络抗粘连创面敷料的制备方法 |
CN105999425A (zh) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | 显影型可降解修复支架 |
CN105999434A (zh) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | 显影型可降解修复输尿管支架 |
CN105999435A (zh) * | 2016-05-24 | 2016-10-12 | 德州海利安生物科技股份有限公司 | 显影型可降解修复尿道支架 |
CN105944153A (zh) * | 2016-05-24 | 2016-09-21 | 德州海利安生物科技股份有限公司 | 显影型可降解修复胆道支架 |
CN106039426A (zh) * | 2016-05-24 | 2016-10-26 | 德州海利安生物科技股份有限公司 | 显影型可降解修复胰管支架 |
CN106668932B (zh) * | 2016-10-24 | 2020-07-10 | 北京化工大学 | 一种止血材料及其制备方法与应用 |
CN115154646B (zh) * | 2022-06-20 | 2023-12-01 | 国科温州研究院(温州生物材料与工程研究所) | 一种可降解止血微球及制备方法与应用 |
CN117899257A (zh) * | 2024-01-12 | 2024-04-19 | 海宁侏罗纪生物科技有限公司 | 一种多糖粉末粘合止血材料及其制备方法 |
-
2009
- 2009-08-05 CN CN2009100179379A patent/CN101632685B/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN101632685A (zh) | 2010-01-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101632685B (zh) | 含有羧基的醛改性多糖在制备药物和医用材料中的应用 | |
Shanmugasundaram et al. | Fabrication and characterization of chicken feather keratin/polysaccharides blended polymer coated nonwoven dressing materials for wound healing applications | |
Fan et al. | Nano-TiO2/collagen-chitosan porous scaffold for wound repairing | |
EP3115068B1 (en) | Wound dressing compositions comprising chitosan and an oxidised cellulose | |
CN101224310B (zh) | 一种载有抗菌药物纳米微粒的医用创伤敷料 | |
EP2695622B1 (en) | A chitosan wound dressing and its method of manufacturing | |
CN105107008B (zh) | 一种羟丁基壳聚糖/氧化海藻酸钠/纳米银复合水凝胶敷料贴 | |
US20110218472A1 (en) | Non drug based wound dressing polymer film and a method of producing the same | |
CN102552964B (zh) | 一种纳米银壳聚糖复合抗菌组合物、创口贴及其制备方法 | |
Khan et al. | Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties | |
CN103265732A (zh) | 壳聚糖-乙基纤维素共混膜及其制备方法、共混凝胶 | |
Türkoğlu et al. | Production of wheat germ oil containing multilayer hydrogel dressing | |
CN101597381A (zh) | 一种用于针后贴的海藻酸钙复合膜医用敷料及其制备方法和应用 | |
CN106975098A (zh) | 一种复合多糖止血组合物及其制备方法与应用 | |
CN202920687U (zh) | 一种皮肤创面生物诱导活性敷料及医用敷料复合物 | |
CA2606066A1 (en) | Photostable wound dressing materials and methods of production thereof | |
Zubair et al. | Emerging trends and challenges in polysaccharide derived materials for wound care applications: A review | |
Sadeghianmaryan et al. | Advancements in 3D-printable polysaccharides, proteins, and synthetic polymers for wound dressing and skin scaffolding–A review | |
CN106729929A (zh) | 一种医用敷料贴及其制备方法 | |
JP5805522B2 (ja) | 粉粒状複合体及び創傷被覆材 | |
Lopes et al. | Renewable Polymers in Biomedical Applications: From the Bench to the Market | |
Zahedi et al. | ANtimicrobial electrospun membranes | |
Radoor et al. | Biobased materials in wound dressings | |
CN110327482A (zh) | 一种医用敷料片、由其制备得到的医用敷料装置及制备方法 | |
Fareez et al. | Nanocellulose nanocomposites for biomedical applications |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120704 |
|
CF01 | Termination of patent right due to non-payment of annual fee |