CN111110926A - 一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 - Google Patents
一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 Download PDFInfo
- Publication number
- CN111110926A CN111110926A CN202010086157.6A CN202010086157A CN111110926A CN 111110926 A CN111110926 A CN 111110926A CN 202010086157 A CN202010086157 A CN 202010086157A CN 111110926 A CN111110926 A CN 111110926A
- Authority
- CN
- China
- Prior art keywords
- solution
- gel pad
- genipin
- colored gel
- chitosan
- 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.)
- Granted
Links
- 210000004877 mucosa Anatomy 0.000 title claims abstract description 27
- 239000000499 gel Substances 0.000 claims abstract description 42
- AZKVWQKMDGGDSV-UHFFFAOYSA-N genipin Natural products COC(=O)C1=COC(O)C2C(CO)=CCC12 AZKVWQKMDGGDSV-UHFFFAOYSA-N 0.000 claims abstract description 40
- AZKVWQKMDGGDSV-BCMRRPTOSA-N Genipin Chemical compound COC(=O)C1=CO[C@@H](O)[C@@H]2C(CO)=CC[C@H]12 AZKVWQKMDGGDSV-BCMRRPTOSA-N 0.000 claims abstract description 39
- 229920001661 Chitosan Polymers 0.000 claims abstract description 37
- 108010010803 Gelatin Proteins 0.000 claims abstract description 28
- 239000008273 gelatin Substances 0.000 claims abstract description 28
- 229920000159 gelatin Polymers 0.000 claims abstract description 28
- 235000019322 gelatine Nutrition 0.000 claims abstract description 28
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 28
- 108010022355 Fibroins Proteins 0.000 claims abstract description 24
- AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 claims abstract description 15
- 230000002496 gastric effect Effects 0.000 claims abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 16
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 230000006196 deacetylation Effects 0.000 claims description 4
- 238000003381 deacetylation reaction Methods 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 230000032798 delamination Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000002224 dissection Methods 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 210000004876 tela submucosa Anatomy 0.000 abstract description 18
- 230000001575 pathological effect Effects 0.000 abstract description 7
- 210000001519 tissue Anatomy 0.000 abstract description 7
- 230000003013 cytotoxicity Effects 0.000 abstract description 3
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 239000011344 liquid material Substances 0.000 abstract description 2
- 210000003205 muscle Anatomy 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000004132 cross linking Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 75
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229960000907 methylthioninium chloride Drugs 0.000 description 4
- 230000003387 muscular Effects 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 238000012323 Endoscopic submucosal dissection Methods 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 239000012154 double-distilled water Substances 0.000 description 3
- 238000012326 endoscopic mucosal resection Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000000703 high-speed centrifugation Methods 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 208000033386 Buerger disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical group C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 description 1
- IBFYXTRXDNAPMM-FZEIBHLUSA-N Geniposide Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@H]2[C@@H]1CC=C2CO IBFYXTRXDNAPMM-FZEIBHLUSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- VGLLGNISLBPZNL-RBUKDIBWSA-N arborescoside Natural products O=C(OC)C=1[C@@H]2C([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)=C(CO)CC2 VGLLGNISLBPZNL-RBUKDIBWSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012325 curative resection Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000012143 endoscopic resection Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- -1 hydroxide ions Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/045—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/18—Materials at least partially X-ray or laser opaque
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Abstract
本发明涉及生物医学工程领域,公开了一种用于消化道粘膜分层的可注射有色凝胶垫及其应用。本发明通过先在消化道粘膜下层注射丝素蛋白溶液、壳聚糖溶液或明胶溶液,然后再注射含有磷酸甘油二钠的京尼平溶液,发生交联反应后在消化道粘膜下层形成凝胶垫,用于将病变粘膜层与肌肉层分离,方便病变粘膜层剥离。本发明可通过控制京尼平溶液中京尼平和磷酸甘油二钠的用量控制凝胶垫的形成时间。本发明中所采用的材料均为低细胞毒性、高度生物相容性的液体材料,且形成的凝胶垫为深蓝色,能够清晰的标出病变组织,使粘膜剥离术更加方便安全,具有很好的临床使用效果,值得临床推广。
Description
技术领域
本发明涉及生物医学工程领域,涉及一种用于消化道粘膜分层的可注射有色凝胶垫及其应用。
背景技术
早期消化道癌是指消化道癌病变位于黏膜或黏膜下层,而不论病灶大小和是否有淋巴结转移。内镜粘膜切除术(EMR)能够对消化道早癌进行内镜下切除,切除范围包括粘膜层、部分粘膜下层及癌组织周围部分正常黏膜。内镜粘膜下剥离术(ESD)是在EMR技术的基础上发展而来,目前临床治疗结果显示ESD可提高一次性完整切除率和组织学治愈性切除率,是一种治疗早期消化道癌的安全有效的方法,已成为早期消化道癌首选的治疗手段之一。但内镜下电凝/电切无蒂及亚蒂肿瘤或者息肉有一定的穿孔风险,采取的预防措施是于病变基底部注射液体垫,使粘膜层与肌层分离,将病变粘膜托起,形成一层保护性粘膜下水垫,使局部粘膜下层厚度增加,粘膜层与肌层分离,电阻增大,让高频电、微波、氩气刀凝固作用仅局限于粘膜下层,避免了破坏肌层及以下的组织,有助保证治疗的安全和有效,极大地降低了穿孔的发生率。
临床上最常用的粘膜下注射液体垫为生理盐水,其次还有15%葡萄糖、甘油、甘露醇及甘油果糖等注射剂。生理盐水的优点是价廉和易获取,但吸收过快,粘膜下注射5mL生理盐水经过45s后可吸收约一半,具有隆起时间短、需要反复注射的缺点。由于生理盐水、15%葡萄糖、甘油、甘露醇及甘油果糖等注射剂都是无色液体,因此产生的垫层与周围组织的界限不清晰,医生操作很不方便。为了使手术视野清晰,临床医生往往在注射剂中加入一定量的亚甲基蓝作为染色剂,来提高垫层界限的清晰度。虽然亚甲基蓝可作为化学指示剂、染料、生物染色剂和药物使用,在临床上常用于治疗尿路结石、闭塞性脉管炎、神经性皮炎,但世界卫生组织国际癌症研究机构把亚甲基蓝列于3类致癌物清单中,因此目前临床作为生物显色剂来使用是不科学的。
发明内容
有鉴于此,本发明的目的是提供一种用于消化道粘膜分层的可注射有色凝胶垫及其应用,用于制备有色凝胶垫的原材料可以通过注射到达消化道粘膜下层,且能在消化道粘膜下层中快速由液体变成凝胶垫,把病变粘膜托起,凝胶垫为蓝色,能够在手术过程中帮助清晰标出病变组织。
为解决上述技术问题,本发明提供了一种用于消化道粘膜分层的可注射有色凝胶垫,所述有色凝胶垫由A溶液与B溶液混合制备而成,其中,所述A溶液为丝素蛋白溶液、壳聚糖溶液或明胶溶液,所述B溶液为京尼平溶液;所述A溶液与所述B溶液的体积比为(1~4):1;
所述丝素蛋白溶液中丝素蛋白的含量为4~6wt%;
所述壳聚糖溶液的pH为5~7,所述壳聚糖溶液中壳聚糖的含量为1~2wt%;
所述明胶溶液中明胶的含量为2~4wt%;
所述京尼平溶液中京尼平的含量为1wt%。
京尼平(Genipin)是栀子苷经β-葡萄糖苷酶水解后的产物,是一种优良的天然生物交联剂,可以与蛋白质、胶原、明胶和壳聚糖等交联制作生物材料,如人造骨骼、伤口包扎材料等,其毒性远低于戊二醛和其他常用化学交联剂。同时它还可用于治疗肝脏疾病、降压、通便等。京尼平作为一种具极低的细胞毒性、高度生物相容性的通过交联氨基的生物交联剂,可以说完全符合再生医药领域的要求。
优选的,所述丝素蛋白溶液中丝素蛋白的含量为3wt%。
优选的,所述壳聚糖溶液中壳聚糖的含量为1wt%。
优选的,所述明胶溶液中明胶的含量为3wt%。
优选的,所述京尼平溶液中还含有磷酸甘油二钠,以所述京尼平溶液的总重量计,所述磷酸甘油二钠的含量为0.6wt%。向京尼平溶液中加入磷酸甘油二钠有助于快速生成凝胶。
优选的,以所述有色凝胶垫的总重量计,所述有色凝胶垫中京尼平的含量为0.15~0.5wt%。当京尼平的含量占凝胶垫总重量的0.15~0.5%,且京尼平溶液中磷酸甘油二钠的含量为0.6wt%时,成胶的时间可控制在30秒至5分钟之间。
优选的,所述壳聚糖溶液由以下方法制备得到:将脱乙酰度为75~99%、分子量为10~100KDa、粘度为30~80cP的壳聚糖粉末溶于质量浓度为1%的乳酸溶液后离心去除未溶物和杂质,得到壳聚糖溶液。考虑到生物安全性,溶液为中性最佳。因此在制备壳聚糖溶液时,乳酸的浓度要尽量低,因此采用质量浓度为1%的乳酸溶液。当壳聚糖溶液中壳聚糖的含量为1~2wt%,乳酸的质量浓度为1%时,壳聚糖溶液的pH为6左右。除此之外,采用脱乙酰度为75~99%、分子量为10~100KDa、粘度为30~80cP的壳聚糖粉末制备壳聚糖溶液可以使溶液具有较好的流动性可以通过注射快速到达消化道粘膜下层。
优选的,所述明胶溶液的溶质为药用明胶。
本发明还提供了上述有色凝胶垫在胃黏膜剥离离术、食道粘膜剥离术和肠道粘膜剥离术中的应用。
优选的,将A溶液注射到消化道粘膜下层后,再将B溶液注射到A溶液中,然后形成将病变粘膜托起的有色凝胶垫。
与现有技术相比,本发明具有以下技术效果:
1)通过先在消化道粘膜下层注射丝素蛋白溶液、壳聚糖溶液或明胶溶液,然后再注射京尼平溶液,在弱酸性和中性条件下,蛋白质或壳聚糖上氨基基团首先对京尼平上烯碳原子展开亲核攻击,其次是开放二氢吡喃环并受二次氨基攻击形成醛基。在碱性条件下,京尼平的开环反应是经由溶液中氢氧根离子亲核攻击,发生羟醛缩合形成中间体醛基。最后,京尼平上醛基又和氨基发生希夫反应形成交联网络后在消化道粘膜下层形成凝胶垫,将病变粘膜托起,使得病变粘膜层与肌肉层分离,方便病变粘膜层剥离。
2)本发明中形成的凝胶垫是半固态状,凝胶垫的高度不会因为刀片的切割而下降。
3)本发明通过实验的得出结论,当京尼平的含量占凝胶垫总重量的0.15~0.5%,且京尼平溶液中磷酸甘油二钠的含量为0.6wt%时,成胶的时间可控制在30秒至5分钟之间,因此,可以根据手术需求,改变京尼平溶液中京尼平和磷酸甘油二钠的用量以控制成胶时间。
4)本发明中所采用的材料均为低细胞毒性、高度生物相容性的液体材料,且形成的凝胶垫为深蓝色,能够清晰的标出病变组织,使粘膜剥离术更加方便安全。
具体实施方式
为了进一步理解本发明,下面结合实施例对本发明优选实施方案进行描述,但是应当理解,这些描述只是为了进一步说明本发明的特征和优点,而不是对本发明权利要求的限制。
本发明所有原料,对其来源没有特别限制,在市场上购买的或按照本领域技术人员熟知的常规方法制备的即可。
为了进一步说明本发明,下面结合实施例对本发明提供的一种基于京尼平可注射消化道粘膜下凝胶垫及制备和应用进行详细描述。
试验动物:长白猪,25-30公斤,公母各半,试验部位选取猪小肠。
实施例1
京尼平溶液、丝素蛋白溶液、壳聚糖溶液和明胶溶液的制备。
京尼平溶液的制备:将10g京尼平和6g磷酸甘油二钠溶解于1000g双蒸水中,得到含有磷酸甘油二钠的京尼平溶液,在含有磷酸甘油二钠的京尼平溶液中,京尼平的含量为1wt%,磷酸甘油二钠的含量为0.6wt%。
丝素蛋白溶液:将4g丝素蛋白溶解于100g双蒸水中制备得到丝素蛋白溶液,丝素蛋白溶液中丝素蛋白的含量为4wt%。
其中,丝素蛋白按以下方式制备:
称取40~50g蚕丝纤维到一定容积的容器中,加入2000ml质量浓度为0.5%碳酸钠碱性溶液,加热煮沸30min,用三蒸水洗涤两次,然后再按上述步骤重复两次,一共煮沸三次,用三蒸水洗涤,直至中性,至于通风橱晾干。用无水氯化钙、水和无水乙醇的三元溶液,其中无水氯化钙:水:无水乙醇的摩尔比为1:8:2,溶解上述丝素蛋白溶液,溶解后通过透析袋(8000-14000)透析3天,除去盐分子得到丝素蛋白溶液。经冷冻干燥得到纯丝素蛋白。
壳聚糖溶液的制备:将1g低粘度壳聚糖粉末(脱乙酰度为75~99%,分子量为10~100KDa,粘度为30~80cP)用99g质量浓度为1%的乳酸溶解,通过高速离心,去除未溶物和杂质,得壳聚糖溶液,壳聚糖溶液中壳聚糖的含量为1wt%。pH为6左右。
明胶溶液的制备:将3g药用明胶用97g双蒸水加热至40℃溶解成药用明胶溶液,通过高速离心,去除未溶物和杂质,得明胶溶液。明胶溶液中,药用明胶的含量为3wt%。
实施例2
取5毫升实施例1制备的质量浓度为3%的药用明胶溶液通过注射器注射到离体猪小肠粘膜下层后,再将1.5毫升实施例1制备的京尼平溶液注射到上述药用明胶溶液中,2分钟以后形成半固态状的深蓝色凝胶垫,把粘膜托起。
实施例3
取5毫升实施例1制备的壳聚糖溶液通过注射器注射到离体猪小肠粘膜下层后,再将2.5毫升实施例1制备的京尼平溶液注射到上述壳聚糖溶液中,1分钟以后形成半固态状的深蓝色凝胶垫,把病变粘膜托起。
实施例4
取5毫升实施例1制备的丝素蛋白溶液通过注射器注射到离体猪小肠粘膜下层后,再将5毫升实施例1制备的京尼平溶液注射到上述丝素蛋白溶液中,30秒以后形成半固态状的深蓝色凝胶,把病变粘膜托起。
综上所述,本发明可通过将明胶溶液、丝素蛋白溶液和壳聚糖溶液中的一种注射到消化道粘膜下层,譬如胃黏膜、食道粘膜或肠道粘膜等,然后再注射京尼平溶液(含有磷酸甘油二钠),能够快速在消化道粘膜下层生成半固态状的深蓝色凝胶垫,把病变粘膜托起,且可清晰的标出待剥离组织。
本发明中所描述的具体实施例仅仅是对本发明精神作举例说明。本发明所属技术领域的技术人员可以对所描述的具体实施例做各种各样的修改或补充或采用类似的方式替代,但并不会偏离本发明的精神。
Claims (10)
1.一种用于消化道粘膜分层的可注射有色凝胶垫,其特征在于,所述有色凝胶垫由A溶液与B溶液混合制备而成,其中,所述A溶液为丝素蛋白溶液、壳聚糖溶液或明胶溶液,所述B溶液为京尼平溶液;所述A溶液与所述B溶液的体积比为(1~4):1;
所述丝素蛋白溶液中丝素蛋白的含量为4~6wt%;
所述壳聚糖溶液的pH为5~7,所述壳聚糖溶液中壳聚糖的含量为1~2wt%;
所述明胶溶液中明胶的含量为2~4wt%;
所述京尼平溶液中京尼平的含量为1wt%。
2.根据权利要求1所述的有色凝胶垫,其特征在于,所述丝素蛋白溶液中丝素蛋白的含量为4wt%。
3.根据权利要求1所述的有色凝胶垫,其特征在于,所述壳聚糖溶液中壳聚糖的含量为1wt%。
4.根据权利要求1所述的有色凝胶垫,其特征在于,所述明胶溶液中明胶的含量为3wt%。
5.根据权利要求1所述的有色凝胶垫,其特征在于,所述京尼平溶液中还含有磷酸甘油二钠,以所述京尼平溶液的总重量计,所述磷酸甘油二钠的含量为0.6wt%。
6.根据权利要求5所述的有色凝胶垫,其特征在于,以所述有色凝胶垫的总重量计,所述有色凝胶垫中京尼平的含量为0.15~0.5wt%。
7.根据权利要求1所述的有色凝胶垫,其特征在于,所述壳聚糖溶液由以下方法制备得到:将脱乙酰度为75~99%、分子量为10~100KDa、粘度为30~80cP的壳聚糖粉末溶于质量浓度为1%的乳酸溶液后离心去除未溶物和杂质,得到壳聚糖溶液。
8.根据权利要求1所述的有色凝胶垫,其特征在于,所述明胶溶液的溶质为药用明胶。
9.一种权利要求1~8任一项所述有色凝胶垫在胃黏膜剥离离术、食道粘膜剥离术和肠道粘膜剥离术中的应用。
10.根据权利要求9所述的有色凝胶垫的应用,其特征在于,将A溶液注射到消化道病变粘膜下层后,再将B溶液注射到A溶液中,然后形成将病变粘膜托起的有色凝胶垫。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010086157.6A CN111110926B (zh) | 2020-02-11 | 2020-02-11 | 一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010086157.6A CN111110926B (zh) | 2020-02-11 | 2020-02-11 | 一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111110926A true CN111110926A (zh) | 2020-05-08 |
CN111110926B CN111110926B (zh) | 2022-04-01 |
Family
ID=70492494
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010086157.6A Active CN111110926B (zh) | 2020-02-11 | 2020-02-11 | 一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111110926B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111588916A (zh) * | 2020-06-03 | 2020-08-28 | 中国人民解放军陆军军医大学第二附属医院 | 一种可注射水凝胶、制备方法及其用途 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102065849A (zh) * | 2008-04-24 | 2011-05-18 | 麦德托尼克公司 | 基于壳聚糖和氧化多糖的保护性凝胶 |
CN102327643A (zh) * | 2011-08-23 | 2012-01-25 | 赵文 | 一种用于骨组织再生的生物支架 |
CN103524795A (zh) * | 2012-07-06 | 2014-01-22 | 中国科学院大连化学物理研究所 | 一种温敏型可注射壳聚糖水凝胶产品及其应用 |
CN104922734A (zh) * | 2015-05-21 | 2015-09-23 | 东南大学 | 促进心肌修复的可注射壳聚糖复合水凝胶及其制备方法 |
CN106496598A (zh) * | 2015-09-30 | 2017-03-15 | 四川大学 | 高生物活性的壳聚糖水凝胶及其制备方法与用途 |
US20180110797A1 (en) * | 2016-10-21 | 2018-04-26 | Covidien Lp | Injectable scaffold for treatment of intracranial aneurysms and related technology |
CN110339155A (zh) * | 2019-07-09 | 2019-10-18 | 广州医科大学 | 巯基化壳聚糖/明胶/β-甘油磷酸钠复合水凝胶及其制备方法 |
-
2020
- 2020-02-11 CN CN202010086157.6A patent/CN111110926B/zh active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102065849A (zh) * | 2008-04-24 | 2011-05-18 | 麦德托尼克公司 | 基于壳聚糖和氧化多糖的保护性凝胶 |
US20140073601A1 (en) * | 2008-04-24 | 2014-03-13 | Medtronic, Inc. | Method for treating the ear, nose or throat |
CN102327643A (zh) * | 2011-08-23 | 2012-01-25 | 赵文 | 一种用于骨组织再生的生物支架 |
CN103524795A (zh) * | 2012-07-06 | 2014-01-22 | 中国科学院大连化学物理研究所 | 一种温敏型可注射壳聚糖水凝胶产品及其应用 |
CN104922734A (zh) * | 2015-05-21 | 2015-09-23 | 东南大学 | 促进心肌修复的可注射壳聚糖复合水凝胶及其制备方法 |
CN106496598A (zh) * | 2015-09-30 | 2017-03-15 | 四川大学 | 高生物活性的壳聚糖水凝胶及其制备方法与用途 |
US20180110797A1 (en) * | 2016-10-21 | 2018-04-26 | Covidien Lp | Injectable scaffold for treatment of intracranial aneurysms and related technology |
CN110339155A (zh) * | 2019-07-09 | 2019-10-18 | 广州医科大学 | 巯基化壳聚糖/明胶/β-甘油磷酸钠复合水凝胶及其制备方法 |
Non-Patent Citations (1)
Title |
---|
施言等: "经内镜粘膜下注射自体血溶液用于EMR和ESD的临床研究", 《湖北民族学院学报 医学版》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111588916A (zh) * | 2020-06-03 | 2020-08-28 | 中国人民解放军陆军军医大学第二附属医院 | 一种可注射水凝胶、制备方法及其用途 |
Also Published As
Publication number | Publication date |
---|---|
CN111110926B (zh) | 2022-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3133095B2 (ja) | 消化器病変組織の硬化剤 | |
US20220040093A1 (en) | Composition for use in the treatment of lesions in the mucosa by means of endoscopic resection | |
JP2001192336A (ja) | 高粘性物質を用いた内視鏡的粘膜切除術 | |
KR102240165B1 (ko) | 점막하 국주용 콜라겐 졸 | |
CN111110926B (zh) | 一种用于消化道粘膜分层的可注射有色凝胶垫及其应用 | |
CN107456612A (zh) | 黏膜下注射溶液 | |
CN114159586A (zh) | 一种内镜用粘膜下注射标记物载体凝胶及其应用 | |
EP3639862A1 (en) | Liquid-phase composition containing alginic acid or pharmaceutically acceptable salt thereof and colloidal polysaccharide | |
KR20130079297A (ko) | 폴록사머 407 및 폴록사머 188을 포함하는 주사제 | |
KR20150131864A (ko) | 어류의 정액 또는 정소로부터 분리된 디엔에이 단편 혼합물을 함유하는 회전근개 파열의 예방 또는 치료용 약학 조성물 | |
CN111991620A (zh) | 一种内镜用粘膜下注射溶液组合物及制备方法 | |
EP1308164B1 (en) | Medical composition comprising a polysaccharide for elevating the epithelium | |
CN104721810B (zh) | 类弹性蛋白多肽制备的软组织分离制剂及应用 | |
JPH07206888A (ja) | 胎盤抽出物およびその製造方法 | |
WO2021146291A1 (en) | Self-assembling peptide gel formulation and methods of use | |
Hikichi et al. | Gastric endoscopic submucosal dissection using sodium carboxymethylcellulose as a new injection substance | |
CN110511930A (zh) | Sal-miR-58及其在抑制血管炎性反应和动脉瘤形成中的用途 | |
JPWO2005037292A1 (ja) | 糖鎖含有キトサン誘導体を含有する内視鏡手術用粘膜下膨隆液組成物 | |
RU2410035C1 (ru) | Способ эндоскопического гемостаза при гастродуоденальных кровотечениях | |
CN101138543B (zh) | 积雪草总苷局部成膜凝胶组合物及其应用 | |
CN116159191B (zh) | 一种用于内镜黏膜下剥离术的温敏型黏膜下注射液的制备方法 | |
CN111228295B (zh) | 一种甲状腺消融隔离液 | |
RU2781332C1 (ru) | Способ эндоскопического лечения химических ожогов пищевода | |
CN115040501B (zh) | 顺-13-十八碳烯酸或其盐化合物在制备促进受损皮肤和/或黏膜愈合的药物中的应用 | |
CN106267379A (zh) | 羟乙基淀粉在内镜下手术中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
EE01 | Entry into force of recordation of patent licensing contract | ||
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20200508 Assignee: NANTONG EGENS BIOTECHNOLOGY Co.,Ltd. Assignor: NANTONG University Contract record no.: X2023980046726 Denomination of invention: An injectable colored gel pad for layering of digestive tract mucosa and its application Granted publication date: 20220401 License type: Common License Record date: 20231114 |