CN113521400A - 一种肿瘤切割吻合器钛钉及其制备方法 - Google Patents
一种肿瘤切割吻合器钛钉及其制备方法 Download PDFInfo
- Publication number
- CN113521400A CN113521400A CN202110664365.4A CN202110664365A CN113521400A CN 113521400 A CN113521400 A CN 113521400A CN 202110664365 A CN202110664365 A CN 202110664365A CN 113521400 A CN113521400 A CN 113521400A
- Authority
- CN
- China
- Prior art keywords
- nail
- soaking
- tumor
- titanium nail
- anastomosis
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 44
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229910052719 titanium Inorganic materials 0.000 title claims abstract description 35
- 239000010936 titanium Substances 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title abstract description 14
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims abstract description 26
- 229960000485 methotrexate Drugs 0.000 claims abstract description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 50
- 230000003872 anastomosis Effects 0.000 claims description 45
- 238000002791 soaking Methods 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 23
- 238000001035 drying Methods 0.000 claims description 22
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 16
- PNROREDTZJCOHF-UHFFFAOYSA-N 2-(3,5-dichlorophenoxy)acetonitrile Chemical compound ClC1=CC(Cl)=CC(OCC#N)=C1 PNROREDTZJCOHF-UHFFFAOYSA-N 0.000 claims description 15
- 230000033444 hydroxylation Effects 0.000 claims description 15
- 238000005805 hydroxylation reaction Methods 0.000 claims description 15
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 238000004381 surface treatment Methods 0.000 claims description 9
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000004140 cleaning Methods 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims 12
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 abstract description 18
- 210000004881 tumor cell Anatomy 0.000 abstract description 10
- 108010024636 Glutathione Proteins 0.000 abstract description 9
- 229960003180 glutathione Drugs 0.000 abstract description 9
- 208000007660 Residual Neoplasm Diseases 0.000 abstract description 7
- 230000035755 proliferation Effects 0.000 abstract description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000002271 resection Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
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
- A61L31/08—Materials for coatings
-
- 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
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- 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
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- 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
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种肿瘤切割吻合器钛钉及其制备方法,包括钛钉,钛钉表面修饰有肿瘤药物释放层。本发明所制备的吻合钉能够在使用吻合器切除肿瘤后,残余肿瘤细胞的增殖会高表达谷胱甘肽,从而致使CysM中的二硫键断裂,从而致使甲氨蝶呤释放,进一步清除残存的肿瘤细胞,预防肿瘤复发。
Description
技术领域
本发明涉及吻合器及其制备方法,特别是涉及一种肿瘤切割吻合器钛钉及其制备方法。
背景技术
肿瘤的吻合器切割是肿瘤手术切除手段的一种升级,较传统的手术切除,操作更简便易行、出血少、手术时间短,具有一定优势。但是肿瘤具有侵袭、转移特性,以及考虑到肿瘤切除后病人机体的正常生理功能,往往会导致有部分肿瘤细胞残余,然而这些残余肿瘤有可能会重新发展成为新的实体瘤,从而形成更加恶性的肿瘤。
通常情况下,术后会对病人进行化疗,以巩固治疗结果,但是无论是口服药还是注射制剂,都要经历复杂的血液循环系统以及体内的生物学屏障,大大降低药物利用效率并会导致用,从而限制了化疗疗效。而吻合器切割后,钛钉会存留在体内的原肿瘤病灶部位,如果将化疗药物结合到钛钉表面,持续释放抗肿瘤药物,可以起到提高药物利用效率、减缓毒副作用的目的,进一步清除参与肿瘤细胞,防止复发。
发明内容
发明目的:本发明的目的是提供一种肿瘤切割吻合器钛钉及其制备方法,该吻合器钛钉可以在肿瘤切除后,在体内持续释放甲氨蝶呤,进一步清除肿瘤细胞,有效预防肿瘤复发。
技术方案:本发明所述的一种肿瘤切割吻合器钛钉,其包括钛钉,钛钉表面修饰有肿瘤药物释放层。
其中,所述释放层通过含二硫键的中间体将抗肿瘤药甲氨蝶呤修饰到钛钉的表面。
上述肿瘤切割吻合器钛钉制备方法包括以下步骤:
(1)对吻合钉进行表面羟基化处理;
(2)将羟基化的吻合钉放入3-羧丙基三乙氧烷丙酮溶液中浸泡,搅拌、浸泡处理后用丙酮冲洗并烘干;
(3)将上述吻合钉浸泡在含有L-胱氨酸二甲酯二盐酸盐、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、N-羟基琥珀酰亚胺(NHS)的水溶液中,搅拌、浸泡后取出用去离子水冲洗并烘干;
(4)将上述吻合钉浸泡在含有甲氨蝶呤、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、N-羟基琥珀酰亚胺的丙酮溶液中,搅拌、浸泡处理后清洗烘干,即可。
优选地,步骤(1)中,将吻合钉置于等离子表面处理仪,控制温度10~30℃,功率2~10Kw,时间10~30min,对吻合钉进行表面羟基化处理。
步骤(2)中,溶液中3-羧丙基三乙氧烷丙酮的浓度为0.1~5mol/L,浸泡1~2h,反应温度为40~80℃。
步骤(3)中,L-胱氨酸二甲酯二盐酸盐的浓度为0.5~2mol/L,L-胱氨酸二甲酯二盐酸盐、EDC、NHS的摩尔比为1∶(1~1.5)∶(1~1.5),反应时间为8~24h,反应温度为10~40℃
步骤(4)中,甲氨蝶呤的浓度为0.1~2mol/L,甲氨蝶呤、EDC、NHS的摩尔比为1∶(1~1.2)∶(1~1.2),反应时间为12~24h,反应温度为25~60℃。
其中,该吻合钉的表面结构如下:
具体制备过程的原理如下:
(a)吻合钉的表面羟基化
利用等离子体表面处理仪对吻合钉进行表面羟基化处理;
(b)钛钉的表面处理
将羟基化的吻合钉依次在下述三种溶液中浸泡:①3-羧丙基三乙氧烷丙酮溶液;②L-胱氨酸二甲酯二盐酸盐(简写为:CysM)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、N-羟基琥珀酰亚胺(NHS)的水溶液;③甲氨蝶呤、EDC、NHS的水溶液。每一步都进行洗涤烘干处理。
本发明中的钛钉通过二硫键修饰抗肿瘤药物甲氨蝶呤,能够在肿瘤切割手术后持续释放甲氨蝶呤,进一步清除残余肿瘤细胞。该钛钉能够在肿瘤切除后,会因肿瘤部位高表达的谷胱甘肽的作用而释放甲氨蝶呤。
本发明的主要目的是对目前已有的肿瘤切割吻合器钛钉的功能化修饰,解决吻合器切割只具有手术切割的单一功能的问题。而单一吻合器切割通常易出现癌细胞残留问题,进而导致肿瘤复发。本发明的的钛钉能够在存在癌细胞残留时及时释放甲氨蝶呤,进一步清除残余肿瘤细胞,有效预防肿瘤复发。
有益效果:本发明所制备的吻合钉能够在使用吻合器切除肿瘤后,残余肿瘤细胞的增殖会高表达谷胱甘肽,从而致使CysM中的二硫键断裂,从而致使甲氨蝶呤释放,进一步清除残存的肿瘤细胞,预防肿瘤复发。
附图说明
图1是按实施例制备的吻合钉在不同浓度的谷胱甘肽溶液中释放甲氨蝶呤的累积量随时间变化曲线。
具体实施方式
下面结合实施例对本发明进一步地详细描述。
本发明提供了一种可术后进一步清除残余肿瘤细胞的肿瘤切割吻合器钛钉,其制备方法如下:
制备过程具体包括如下五个步骤:
(a)利用等离子体表面处理仪对吻合钉进行表面羟基化处理;
(b)将羟基化的吻合钉放入3-羧丙基三乙氧烷丙酮溶液中浸泡1~2h,浸泡完后用丙酮冲洗并烘干;
(c)将上述吻合钉浸泡在含有足量L-胱氨酸二甲酯二盐酸盐(简写为:CysM)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、N-羟基琥珀酰亚胺(NHS)的水溶液中24h,取出后用去离子水冲洗并烘干;
(d)将上述吻合钉浸泡在含有足量甲氨蝶呤(简写为:Met)、EDC、NHS的丙酮溶液中24h,取出后依次用丙酮、去离子水冲洗三次并烘干。
实施例1
一种肿瘤切割吻合器钛钉的制备方法,包括如下步骤:
1)吻合钉的表面羟基化
将吻合钉置于EPT-02等离子表面处理仪,控制温度25℃,功率5Kw,时间20min,处理气氛为真空条件,等离子体为氧气的等离子体,对吻合钉进行表面羟基化处理;
2)将羟基化的吻合钉放入浓度为2mol/L的3-羧丙基三乙氧烷丙酮溶液中,50℃下搅拌、浸泡2h,然后用丙酮冲洗并烘干;
3)将上述吻合钉浸泡在含有1mol/L的L-胱氨酸二甲酯二盐酸盐、1.1mol/L的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、1.1mol/L的N-羟基琥珀酰亚胺(NHS)的水溶液中30℃下,搅拌、浸泡12h,然后取出用去离子水冲洗并烘干;
4)将上述吻合钉浸泡在含有0.5mol/L甲氨蝶呤、0.6mol/L 1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、0.6mol/L N-羟基琥珀酰亚胺的丙酮溶液中,40℃下,搅拌、浸泡处理18h,然后清洗烘干,即可。
实施例2
一种肿瘤切割吻合器钛钉的制备方法,包括如下步骤:
1)吻合钉的表面羟基化
将吻合钉置于EPT-02等离子表面处理仪,控制温度30℃,功率4Kw,时间15min,处理气氛为真空条件,等离子体为氧气的等离子体,对吻合钉进行表面羟基化处理;
2)将羟基化的吻合钉放入浓度为5mol/L的3-羧丙基三乙氧烷丙酮溶液中,50℃下搅拌、浸泡1.5h,然后用丙酮冲洗并烘干;
3)将上述吻合钉浸泡在含有2mol/L的L-胱氨酸二甲酯二盐酸盐、2.3mol/L的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、2.3mol/L的N-羟基琥珀酰亚胺(NHS)的水溶液中40℃下,搅拌、浸泡12h,然后取出用去离子水冲洗并烘干;
4)将上述吻合钉浸泡在含有2mol/L甲氨蝶呤、2.3mol/L 1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、2.3mol/L N-羟基琥珀酰亚胺的丙酮溶液中,60℃下,搅拌、浸泡处理18h,然后清洗烘干,即可。
实施例3
以pH为7.3的的磷酸缓冲盐溶液(PBS)为溶剂,配置谷胱甘肽浓度为0,2,4,6,8μmol/L的溶液。取5份上述实施例1中制备的钛钉,浸泡在10mL上述谷胱甘肽溶液中,分别在0、0.5、1、2、4、6、8、12、24小时取100μL溶液测量其在303nm处的吸光强度。根据事先测定的甲氨蝶呤浓度与其在303nm处的吸光强度之间关系的标准曲线,求得不同时间点下甲氨蝶呤释放的量。如图1所示,在不存在谷胱甘肽的PBS中,甲氨蝶呤几乎不释放,而在含有谷胱甘肽的PBS中,甲氨蝶呤被快速释放出来。此结果说明本发明所提供的钛钉能够在肿瘤部位高表达的谷胱甘肽诱导下释放甲氨蝶呤的特性,从而可以在术后进一步清除肿瘤细胞,有效预防肿瘤复发。
实施例4
一种肿瘤切割吻合器钛钉的制备方法,包括如下步骤:
1)吻合钉的表面羟基化
将吻合钉置于EPT-02等离子表面处理仪,控制温度10℃,功率10Kw,时间30min,处理气氛为真空条件,等离子体为氧气的等离子体,对吻合钉进行表面羟基化处理;
2)将羟基化的吻合钉放入浓度为0.1mol/L的3-羧丙基三乙氧烷丙酮溶液中,50℃下搅拌、浸泡2h,然后用丙酮冲洗并烘干;
3)将上述吻合钉浸泡在含有1mol/L的L-胱氨酸二甲酯二盐酸盐、1mol/L的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、1mol/L的N-羟基琥珀酰亚胺(NHS)的水溶液中40℃下,搅拌、浸泡8h,然后取出用去离子水冲洗并烘干;
4)将上述吻合钉浸泡在含有0.1mol/L甲氨蝶呤、0.1mol/L 1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、0.1mol/L N-羟基琥珀酰亚胺的丙酮溶液中,60℃下,搅拌、浸泡处理12h,然后清洗烘干,即可。
实施例5
一种肿瘤切割吻合器钛钉的制备方法,包括如下步骤:
1)吻合钉的表面羟基化
将吻合钉置于EPT-02等离子表面处理仪,控制温度20℃,功率2Kw,时间30min,处理气氛为真空条件,等离子体为氧气的等离子体,对吻合钉进行表面羟基化处理;
2)将羟基化的吻合钉放入浓度为1mol/L的3-羧丙基三乙氧烷丙酮溶液中,80℃下搅拌、浸泡1h,然后用丙酮冲洗并烘干;
3)将上述吻合钉浸泡在含有2mol/L的L-胱氨酸二甲酯二盐酸盐、3mol/L的1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、3mol/L的N-羟基琥珀酰亚胺(NHS)的水溶液中10℃下,搅拌、浸泡24h,然后取出用去离子水冲洗并烘干;
4)将上述吻合钉浸泡在含有1mol/L甲氨蝶呤、1.2mol/L 1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、1.2mol/L N-羟基琥珀酰亚胺的丙酮溶液中,25℃下,搅拌、浸泡处理24h,然后清洗烘干,即可。
将上述实施例4、5得到的肿瘤切割吻合器钛钉进行测试,测试结果同实施例1。
Claims (7)
1.一种肿瘤切割吻合器钛钉,其特征在于:包括钛钉,所述钛钉表面修饰有肿瘤药物释放层。
2.根据权利要求1所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:所述释放层通过含二硫键的中间体将抗肿瘤药甲氨蝶呤修饰到钛钉的表面。
3.根据权利要求1或2所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:包括以下步骤:
(1)对吻合钉进行表面羟基化处理;
(2)将羟基化的吻合钉放入3-羧丙基三乙氧烷丙酮溶液中浸泡,搅拌、浸泡处理后用丙酮冲洗并烘干;
(3)将上述吻合钉浸泡在含有L-胱氨酸二甲酯二盐酸盐、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、N-羟基琥珀酰亚胺(NHS)的水溶液中,搅拌、浸泡后取出用去离子水冲洗并烘干;
(4)将上述吻合钉浸泡在含有甲氨蝶呤、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐、N-羟基琥珀酰亚胺的丙酮溶液中,搅拌、浸泡处理后清洗烘干,即可。
4.根据权利要求3所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:步骤(1)中,将吻合钉置于等离子表面处理仪,控制温度为10~30℃,功率为2~10Kw,时间为10~30min,对吻合钉进行表面羟基化处理。
5.据权利要求3所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:步骤(2)中,溶液中3-羧丙基三乙氧烷丙酮的浓度为0.1~5mol/L,浸泡温度为40~80℃,浸泡时间为1~2h。
6.据权利要求3所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:步骤(3)中,L-胱氨酸二甲酯二盐酸盐的浓度为0.5~2mol/L,L-胱氨酸二甲酯二盐酸盐、EDC、NHS的摩尔比为1∶1~1.5∶1~1.5,浸泡时间为8~24h,浸泡温度为10~40℃。
7.据权利要求3所述的肿瘤切割吻合器钛钉的制备方法,其特征在于:步骤(4)中,甲氨蝶呤的浓度为0.1~2mol/L,甲氨蝶呤、EDC、NHS的摩尔比为1∶1~1.2∶1~1.2,浸泡时间为12~24h,浸泡温度为25~60℃。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110664365.4A CN113521400B (zh) | 2021-06-15 | 2021-06-15 | 一种肿瘤切割吻合器钛钉及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110664365.4A CN113521400B (zh) | 2021-06-15 | 2021-06-15 | 一种肿瘤切割吻合器钛钉及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113521400A true CN113521400A (zh) | 2021-10-22 |
CN113521400B CN113521400B (zh) | 2022-04-12 |
Family
ID=78096011
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110664365.4A Active CN113521400B (zh) | 2021-06-15 | 2021-06-15 | 一种肿瘤切割吻合器钛钉及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113521400B (zh) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040186518A1 (en) * | 2003-03-19 | 2004-09-23 | Saeyoung Ahn | Electrochemical therapy apparatus |
CN101180087A (zh) * | 2005-03-25 | 2008-05-14 | 拉布寇特有限公司 | 用于医用装置的可控药物释放涂层 |
CN102083397A (zh) * | 2008-04-17 | 2011-06-01 | 米歇尔技术公司 | 具有生物可吸收层的支架 |
CN102159257A (zh) * | 2008-07-17 | 2011-08-17 | 米歇尔技术公司 | 药物递送医疗设备 |
EP3103401A1 (en) * | 2015-06-08 | 2016-12-14 | Universita Degli Studi Di Perugia | Surgical instrument for colon-rectum operations |
CN109232875A (zh) * | 2018-09-17 | 2019-01-18 | 中山大学 | Cys及其衍生物和聚酯聚合物形成的pH/还原双敏感载体材料及其制备方法和应用 |
-
2021
- 2021-06-15 CN CN202110664365.4A patent/CN113521400B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040186518A1 (en) * | 2003-03-19 | 2004-09-23 | Saeyoung Ahn | Electrochemical therapy apparatus |
CN101180087A (zh) * | 2005-03-25 | 2008-05-14 | 拉布寇特有限公司 | 用于医用装置的可控药物释放涂层 |
CN102083397A (zh) * | 2008-04-17 | 2011-06-01 | 米歇尔技术公司 | 具有生物可吸收层的支架 |
CN102159257A (zh) * | 2008-07-17 | 2011-08-17 | 米歇尔技术公司 | 药物递送医疗设备 |
EP3103401A1 (en) * | 2015-06-08 | 2016-12-14 | Universita Degli Studi Di Perugia | Surgical instrument for colon-rectum operations |
CN109232875A (zh) * | 2018-09-17 | 2019-01-18 | 中山大学 | Cys及其衍生物和聚酯聚合物形成的pH/还原双敏感载体材料及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
CN113521400B (zh) | 2022-04-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Li et al. | Engineering a hydrogen‐sulfide‐based nanomodulator to normalize hyperactive photothermal immunogenicity for combination cancer therapy | |
Lubart et al. | Effects of visible and near-infrared lasers on cell cultures | |
CN103990179B (zh) | 一种制备异种脱细胞基质的方法及其产品 | |
RU2010105646A (ru) | Способ регенерации ткани | |
Li et al. | Nanoenzyme–chitosan hydrogel complex with cascade catalytic and self-reinforced antibacterial performance for accelerated healing of diabetic wounds | |
CN111529720A (zh) | 一种诊疗一体化纳米材料及其制备方法与应用 | |
CN111821282B (zh) | 一种介导级联反应的纳米颗粒及其制备方法 | |
CN113521400B (zh) | 一种肿瘤切割吻合器钛钉及其制备方法 | |
CN107115561A (zh) | 一种3d打印支架材料及其制备方法和应用 | |
CN113084188B (zh) | 一种多功能治疗性生物材料及其制备方法 | |
CN115317607B (zh) | 单原子铁掺杂的石墨相氮化碳纳米复合材料、其制备方法及应用 | |
CN114984303B (zh) | 一种可原位产氧的喷雾式水凝胶敷料、制备方法及应用 | |
Shao et al. | Mn-doped single atom nanozyme composited Au for enhancing enzymatic and photothermal therapy | |
CN108653732B (zh) | pH响应型四氧化三铁纳米粒及其制备方法与应用 | |
CN109331182B (zh) | 一种聚多巴胺修饰的导电高分子纳米材料及其制备方法与应用 | |
Zheng et al. | Synthesis of porphyrin-based 2D ytterbium metal organic frameworks for efficient photodynamic therapy | |
WO2004011631A3 (en) | Methods and compositions for treating tissue defects using pulsed electromagnetic field stimulus | |
CN104771784B (zh) | 一种组织脱细胞液 | |
Fan et al. | Photothermal effect of indocyanine green modified scaffold inhibits oral squamous cell carcinoma and promotes wound healing | |
RU2314806C1 (ru) | Средство для лечения злокачественных опухолей методом фотодинамической терапии | |
CN113289014A (zh) | 超小粒径的两性离子聚肽/没食子酸/铁配位纳米粒子及其制备方法与应用 | |
ES2434040T3 (es) | Procedimiento para producir un agente anticanceroso | |
Giatsidis et al. | Breast tissue engineering: decellularized scaffolds derived from porcine mammary glands | |
CN114917340B (zh) | 具有光热功能的口腔黏膜修复材料及制备方法和应用 | |
CN112190772B (zh) | 一种具有消炎功能的吻合钉及其制备方法 |
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 |
Application publication date: 20211022 Assignee: Jiangsu Maxon automation equipment Co.,Ltd. Assignor: HUAIYIN INSTITUTE OF TECHNOLOGY Contract record no.: X2023980050845 Denomination of invention: A tumor cutting stapler titanium nail and its preparation method Granted publication date: 20220412 License type: Common License Record date: 20231208 |
|
EE01 | Entry into force of recordation of patent licensing contract |