CN108888808A - A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma - Google Patents
A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma Download PDFInfo
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- CN108888808A CN108888808A CN201810967010.0A CN201810967010A CN108888808A CN 108888808 A CN108888808 A CN 108888808A CN 201810967010 A CN201810967010 A CN 201810967010A CN 108888808 A CN108888808 A CN 108888808A
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- Prior art keywords
- photosensitizer
- bracket
- cholangiocarcinoma
- photodynamic therapy
- layer
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- 239000003504 photosensitizing agent Substances 0.000 title claims abstract description 55
- 208000006990 cholangiocarcinoma Diseases 0.000 title claims abstract description 50
- 238000002428 photodynamic therapy Methods 0.000 title claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 28
- 229940079593 drug Drugs 0.000 claims abstract description 22
- 229920000642 polymer Polymers 0.000 claims abstract description 11
- 239000011248 coating agent Substances 0.000 claims description 15
- 238000000576 coating method Methods 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 12
- HLXZNVUGXRDIFK-UHFFFAOYSA-N nickel titanium Chemical compound [Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni] HLXZNVUGXRDIFK-UHFFFAOYSA-N 0.000 claims description 12
- 229910001000 nickel titanium Inorganic materials 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- LYPFDBRUNKHDGX-SOGSVHMOSA-N N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 Chemical compound N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 LYPFDBRUNKHDGX-SOGSVHMOSA-N 0.000 claims description 9
- 229960002197 temoporfin Drugs 0.000 claims description 9
- 229920001610 polycaprolactone Polymers 0.000 claims description 8
- 239000004632 polycaprolactone Substances 0.000 claims description 8
- 238000004659 sterilization and disinfection Methods 0.000 claims description 8
- 229920001661 Chitosan Polymers 0.000 claims description 7
- 229920002988 biodegradable polymer Polymers 0.000 claims description 7
- 239000004621 biodegradable polymer Substances 0.000 claims description 7
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 7
- 239000004626 polylactic acid Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 102000008186 Collagen Human genes 0.000 claims description 6
- 108010035532 Collagen Proteins 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 108010010803 Gelatin Proteins 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 229920001436 collagen Polymers 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- 239000008273 gelatin Substances 0.000 claims description 6
- 229920000159 gelatin Polymers 0.000 claims description 6
- 235000019322 gelatine Nutrition 0.000 claims description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims description 6
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- 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 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 239000000017 hydrogel Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000001523 electrospinning Methods 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 239000004633 polyglycolic acid Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 238000007334 copolymerization reaction Methods 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 20
- 230000003211 malignant effect Effects 0.000 abstract description 8
- 230000035755 proliferation Effects 0.000 abstract description 8
- 208000037803 restenosis Diseases 0.000 abstract description 8
- 238000007910 systemic administration Methods 0.000 abstract description 4
- 206010028980 Neoplasm Diseases 0.000 description 12
- 210000003445 biliary tract Anatomy 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 206010020718 hyperplasia Diseases 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 206010013786 Dry skin Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 206010056375 Bile duct obstruction Diseases 0.000 description 2
- 206010008635 Cholestasis Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 210000000013 bile duct Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
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- 239000003937 drug carrier Substances 0.000 description 2
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- 150000002148 esters Chemical class 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
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- 239000013067 intermediate product Substances 0.000 description 2
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- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 229920004934 Dacron® Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
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- 238000005538 encapsulation Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
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- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
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- 230000004060 metabolic process Effects 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
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- 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
- 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
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular 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
-
- 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
- A61L31/148—Materials at least partially resorbable by the body
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- 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
- A61L2300/224—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials containing metals, e.g. porphyrins, vitamin B12
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- 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
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- 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
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- 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)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma of the invention, the photosensitizer bracket includes rack body；The rack body is equipped with bracket overlay film internal layer；The bracket overlay film internal layer is equipped with drug-loaded layer；The drug-loaded layer includes photosensitizer layer and high polymer layer.Its advantage is shown：Having by bracket prevents narrow effect, additionally by the photodynamic therapy of part, treats to cholangiocarcinoma, reduces the side effect of systemic administration bring, while preventing cholangiocarcinoma malignant proliferation bring restenosis, the effective life quality for improving patient.
Description
Technical field
The present invention relates to the field of medical instrument technology, specifically, being that one kind can be used for photodynamic therapy treatment cholangiocarcinoma
Photosensitizer bracket.
Background technique
Cholangiocarcinoma is initiated by the liver malignancy of epithelium, and early stage is generally asymptomatic, when symptom occur and obtaining diagnosis and treatment
Patient is typically in progressive stage.The treatment of cholangiocarcinoma includes operation, chemicotherapy, optical dynamic therapy.Optical dynamic therapy it is external
Method through being conventional therapy cholangiocarcinoma.The side effect of photodynamic therapy is low, significant effect, can improve life in patients,
Extend patient survival, and generally resisted without treatment, is used in combination also with other therapies without taboo.Implementing the treatment of light power at present
When method, mainly by the approach of intravenously administrable, gathered using targeting of the photosensitizer for tumour, then treated.Vein
The method of administration is mainly the long retention effect of Thief zone for passing through tumour, and targeting is unsatisfactory and expensive.
Temoporfin is a kind of two generation photosensitizers, and excitation wavelength 652nm penetrates tumor tissues depth compared with generation photosensitizer
It is deep.Listing treatment head and neck neoplasm is ratified by European Union at present.This product is mainly distributed on vascular space and is swollen in tumor tissues
In oncocyte, chief destructive be tumor tissues vascular wall and direct killing tumour cell.This product is main in tumour cell
Concentrate on cytoplasm rather than in nucleus.There is clinical research discovery, the photodynamic therapy that Temoporfin mediates can be effectively improved
The life quality of cholangiocarcinoma patients extends the life span of patient.
By biodegradable polymer disclosed in the prior art for example polycaprolactone, polylactic acid, poly- hexanol acid and they
Copolymer, poly- dioxane, collagen, phosphocholine, chitosan, hyaluronic acid and hydrogel, gelatin and its derivative
Deng, have good histocompatbility, degraded in the environment of body fluid by ester linkage hydrolyzing, intermediate product lactic acid be in vivo just
The product of normal glycometabolism, final metabolite are CO2And H2O easily from internal discharge without assembling in vitals, therefore has
There is excellent biodegradable absorbability.Above-mentioned material is nontoxic, nonirritant, non-immunogenicity and biocompatibility are good,
It can be used safely in vivo, to be used as the ideal material of Slow/Controlled Release Drug.
Chinese patent literature CN97231023.1, the applying date 19971231, patent name is：Biliary tract portal area tissue compatible
Property reinforced Y shape inner support, discloses a kind of for treating the novel inner support of the disease of biliary tract such as cholangiocarcinoma.The inner support is in sky
Heart Y-shaped pipeline structure, is made of silica gel internal layer and dacron outer layer, is bonded between ectonexine using special process, internal layer light
It is sliding, be conducive to bile and flow through, outer layer is coarse, is conducive to suture., patient simple with structure it is painful it is small, do not block, be not easy to be formed
The advantages that calculus, can be widely used for treatment disease of biliary tract.But cholangiocarcinoma, hair are treated using photosensitizer carried stent about a kind of
That waves bracket prevents narrow effect, additionally by the photodynamic therapy of part, treats to cholangiocarcinoma.Reduce systemic administration band
The side effect come, while cholangiocarcinoma malignant proliferation bring restenosis is prevented, the technology of the effective life quality for improving patient
Scheme is not disclosed then accordingly.
In conclusion needing one kind to have by bracket prevents narrow effect, it is right additionally by the photodynamic therapy of part
Cholangiocarcinoma is treated, and reduces the side effect of systemic administration bring, while preventing cholangiocarcinoma malignant proliferation bring restenosis, has
The photosensitizer bracket of the life quality of the raising patient of effect, and yet there are no report about this photosensitizer bracket.
Summary of the invention
The purpose of the present invention is aiming at the shortcomings in the prior art, providing a kind of bracket that plays to prevent narrow effect, separately
The outer photodynamic therapy by part, treats cholangiocarcinoma, reduces the side effect of systemic administration bring, while preventing bile duct
Cancer malignant proliferation bring restenosis, the photosensitizer bracket of the effective life quality for improving patient.
Another object of the present invention is：A kind of system of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma is provided
Preparation Method.
To achieve the above object, the technical solution adopted by the present invention is that：
A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that the photosensitizer branch
Frame includes rack body；The rack body is equipped with bracket overlay film internal layer；The bracket overlay film internal layer, which is equipped with, carries medicine
Layer；The drug-loaded layer includes photosensitizer layer and high polymer layer.
As a kind of perferred technical scheme, the rack body is Nitinol precoated metal bracket.
As a kind of perferred technical scheme, the photosensitizer layer uses material to be made for Temoporfin.
As a kind of perferred technical scheme, the material of the high polymer layer uses selected from polycaprolactone, gathers
Lactic acid, poly- hexanol acid and their copolymer, poly- dioxane, collagen, phosphocholine, chitosan, hyaluronic acid and
At least one of hydrogel, gelatin and its derivative.
To realize above-mentioned second purpose, the technical solution adopted by the present invention is that：
A kind of preparation method for the photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma, the preparation method include
Following steps：
It step S1, will be spare after Nitinol overlay film frame 60Co irradiation sterilization；
Step S2, proportionally, biodegradable polymer will be dissolved into dichloromethane or chloroform or tetrahydro furan
Mutter or acetone or carbon tetrachloride or dimethylformamide in, solution is made, photosensitizer is dispersed in the biodegradable
In polymer solution, by mixing electrospinning process, the rack surface of the S1 preparation is set, cholangiocarcinoma photosensitizer is made
Coating stent of medicine；
Step S3, cholangiocarcinoma photosensitizer drug coating bracket obtained in above-mentioned steps S2 is placed in a vacuum drying oven,
31-45 DEG C of drying, and with oxirane disinfection post package.
As a kind of perferred technical scheme, bracket used is Nitinol overlay film frame.
As a kind of perferred technical scheme, the biodegradable polymer is polycaprolactone, polylactic acid, poly- hexanol
Acid, polylactide-polyglycolic acid copolymer, polycaprolactone-copolymer of poly lactic acid, poly- dioxane, collagen, phosphocholine,
Gelatin or chitosan and its derivative are at least one.
The invention has the advantages that：
(1) the photosensitizer drug coating bracket of this treatment cholangiocarcinoma, using Nitinol overlay film frame as raw material, radial support
Better performances can prevent cholangiocarcinoma malignant proliferation to be closed, and keep biliary tract unobstructed；
(2) this bracket coating pharmaceutical carrier is biodegradable polymer, and biocompatibility is preferable, acts in vivo few
Inflammation；
(3) it can be repeated several times row optical dynamic therapy bile duct using the photosensitizer of the polymer coating slow release containing drug
Cancer, anti-cholangiocarcinoma cell malignant proliferation and narrow avoid aggravating obstruction of bile duct after restenosis occurs, are effectively improved survival of patients
Quality.
(4) coating stent of medicine for the treatment of cholangiocarcinoma of the invention can pass through light power partially into cholangiocarcinoma
Therapy effectively prevent the histio-irritative hyperplasia of support portions or the significant hyperplasia of tumor tissues, both improved curative effect decrease it is photosensitive
The systemic side effects of agent intravenously administrable；Which reduce the hyperplasia pathological reaction of local anomaly, avoid aggravating after restenosis occurs
Obstruction.
Detailed description of the invention
Attached drawing 1 is a kind of structural representation of photosensitizer bracket that can be used for photodynamic therapy treatment cholangiocarcinoma of the invention
Figure.
Specific embodiment
It elaborates with reference to the accompanying drawing to specific embodiment provided by the invention.
Appended drawing reference involved in attached drawing and component part are as follows：
1. 11. bracket overlay film internal layer of rack body
12. 13. photosensitizer layer of drug-loaded layer
14. high polymer layer
The structure of 1 photosensitizer bracket of embodiment
Fig. 1 is please referred to, Fig. 1 is a kind of knot of photosensitizer bracket that can be used for photodynamic therapy treatment cholangiocarcinoma of the invention
Structure schematic diagram.A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma, the photosensitizer bracket includes bracket
Ontology 1；The rack body 1 is equipped with bracket overlay film internal layer 11；The bracket overlay film internal layer 11 is equipped with drug-loaded layer 12；
The drug-loaded layer 12 includes photosensitizer layer 13 and high polymer layer 14.
The embodiment it should be noted that：
Photosensitizer bracket of the invention is covered on tumor surface, can be targeted by way of local sustained release into tumor tissues
Interior, the targeting of photodynamic therapy not only can be improved in this, while can effectively reduce drug dose, this also further reduces medicine
The side effect of object, and reduce financial burden.
The rack body 1 is Nitinol precoated metal bracket.With good tension force effect, support effect is good.
The photosensitizer layer 13 uses material to be made for Temoporfin, is treated by the light power that Temoporfin mediates
Method can be effectively improved the life quality of cholangiocarcinoma patients, extend the life span of patient.
The material of the high polymer layer 14 use selected from polycaprolactone, polylactic acid, poly- hexanol acid and they
Copolymer, poly- dioxane, collagen, phosphocholine, chitosan, hyaluronic acid and hydrogel, gelatin and its derivative
Etc. at least one.With good histocompatbility, degraded in the environment of body fluid by ester linkage hydrolyzing, intermediate product lactic acid
It is the product of internal normal sugar metabolism, final metabolite is CO2And H2O, easily from internal discharge without poly- in vitals
Collection, therefore there is excellent biodegradable absorbability.Above-mentioned material is nontoxic, nonirritant, non-immunogenicity and biofacies
Capacitive is good, can be used safely in vivo, to be used as the ideal material of Slow/Controlled Release Drug.
The preparation method (one) of 2 photosensitizer bracket of embodiment
(1) Nitinol peritonaeum bracket is spare after 60Co irradiation sterilization；
(2) in 20mg: 1ml ratio, polycaprolactone is dissolved into acetone, solution is made, by Temoporfin and high score
Sub- material is proportionally dispersed in the polycaprolactone solution, and by spray treatment, setting is prepared in the step (1)
Rack surface, that is, anti-cholangiocarcinoma photosensitizer drug coating bracket is made；
(3) it is placed in a vacuum drying oven after the medication coat preparation of biliary tract prosthesis, 45 DEG C of dryings, and uses ethylene oxide
Sterilize post package.
The preparation method (two) of 3 photosensitizer bracket of embodiment
(1) Nitinol peritonaeum bracket is spare after 60Co irradiation sterilization
(2) according to 80mg：Poly L-lactide-caprolactone is dissolved in hexafluoroisopropanol, is made 8% by the ratio of 1ml
Electrostatic spinning solution.
(3) Temoporfin of 500mg is added in the above solution, is uniformly mixed using magnetic stirring apparatus.
(4) using the method for mixing electrostatic spinning by the solution cospinning of above-mentioned (3) in the surface of Nitinol overlay film frame,
Drug-loading fibre film is made.It is placed in a vacuum drying oven after the medication coat preparation of biliary tract prosthesis, 45 DEG C of dryings, and uses epoxy
Ethane sterilizes post package.
The preparation method (three) of 4 photosensitizer bracket of embodiment
Firstly, nick-eltitanium alloy stent is respectively placed in 60Co irradiation sterilization；Then, in 50mg: 1ml ratio, shell is gathered
Sugar is dissolved into carbon tetrachloride, and solution is made, and the Temoporfin that quality is 500mg is dispersed in the chitosan solution
In, then by electrospinning process, be placed in the rack surface, anti-cholangiocarcinoma photosensitizer drug coating bracket is made；Finally,
Above-mentioned anti-cholangiocarcinoma photosensitizer drug coating bracket is placed in a vacuum drying oven, 45 DEG C of dryings, and with after oxirane disinfection
Encapsulation.
A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma of the invention has the following technical effects：
(1) the photosensitizer drug coating bracket of this treatment cholangiocarcinoma, using Nitinol overlay film frame as raw material, radial support
Better performances can prevent cholangiocarcinoma malignant proliferation to be closed, and keep biliary tract unobstructed；
(2) this bracket coating pharmaceutical carrier is biodegradable polymer, and biocompatibility is preferable, acts in vivo few
Inflammation；
(3) it can be repeated several times row optical dynamic therapy bile duct using the photosensitizer of the polymer coating slow release containing drug
Cancer, anti-cholangiocarcinoma cell malignant proliferation and narrow avoid aggravating obstruction of bile duct after restenosis occurs, are effectively improved survival of patients
Quality.
(4) coating stent of medicine for the treatment of cholangiocarcinoma of the invention can pass through light power partially into cholangiocarcinoma
Therapy effectively prevent the histio-irritative hyperplasia of support portions or the significant hyperplasia of tumor tissues, both improved curative effect decrease it is photosensitive
The systemic side effects of agent intravenously administrable；Which reduce the hyperplasia pathological reaction of local anomaly, avoid aggravating after restenosis occurs
Obstruction.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, under the premise of not departing from the method for the present invention, can also make several improvement and supplement, these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (7)
1. a kind of photosensitizer bracket that can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that the photosensitizer bracket
Including rack body；The rack body is equipped with bracket overlay film internal layer；The bracket overlay film internal layer is equipped with drug-loaded layer；
The drug-loaded layer includes photosensitizer layer and high polymer layer.
2. the photosensitizer bracket according to claim 1 that can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that institute
The rack body stated is Nitinol precoated metal bracket.
3. the photosensitizer bracket according to claim 1 that can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that institute
The photosensitizer layer stated uses material to be made for Temoporfin.
4. the photosensitizer bracket according to claim 1 that can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that institute
The material for the high polymer layer stated is used selected from polycaprolactone, polylactic acid, poly- hexanol acid and their copolymer, poly- two
Six ring of oxygen, collagen, phosphocholine, chitosan, hyaluronic acid and hydrogel, gelatin and its derivative are at least one.
5. a kind of preparation method for the photosensitizer bracket that can be used for photodynamic therapy treatment cholangiocarcinoma, which is characterized in that the system
Preparation Method includes the following steps：
It step S1, will be spare after Nitinol overlay film frame 60Co irradiation sterilization；
Step S2, proportionally, biodegradable polymer will be dissolved into dichloromethane or chloroform or tetrahydrofuran or
In acetone or carbon tetrachloride or dimethylformamide, solution is made, photosensitizer is dispersed in the biodegradable and is polymerize
In object solution, by mixing electrospinning process, the rack surface of the step S1 preparation is set, cholangiocarcinoma photosensitizer is made
Coating stent of medicine；
Step S3, cholangiocarcinoma photosensitizer drug coating bracket obtained in above-mentioned steps S2 is placed in a vacuum drying oven, 31-45
DEG C drying, and with oxirane disinfection post package.
6. the preparation method of the photosensitizer bracket according to claim 5 that can be used for photodynamic therapy treatment cholangiocarcinoma,
It is characterized in that, bracket used is Nitinol overlay film frame.
7. the preparation method of the photosensitizer bracket according to claim 5 that can be used for photodynamic therapy treatment cholangiocarcinoma,
It is characterized in that, the biodegradable polymer is polycaprolactone, polylactic acid, poly- hexanol acid, polylactic acid-polyglycolic acid copolymerization
Object, polycaprolactone-copolymer of poly lactic acid, poly- dioxane, collagen, phosphocholine, gelatin or chitosan and its derivative
Object is at least one.
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| CN201810967010.0A CN108888808A (en) | 2018-08-23 | 2018-08-23 | A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma |
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| CN201810967010.0A CN108888808A (en) | 2018-08-23 | 2018-08-23 | A kind of photosensitizer bracket can be used for photodynamic therapy treatment cholangiocarcinoma |
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| US20090269479A1 (en) * | 2008-04-23 | 2009-10-29 | Abbott Cardiovascular Systems Inc. | Method For Biostable Inclusion Of A Biobeneficial Agent On An Outermost Surface Of An Implantable Medical Device |
| US20120015331A1 (en) * | 2009-03-23 | 2012-01-19 | Simon Wood | Scaffold |
| CN102525697A (en) * | 2011-12-22 | 2012-07-04 | 上海纳米技术及应用国家工程研究中心有限公司 | Medicine-carrying membrane-covered stent and preparation method thereof |
| CN102727944A (en) * | 2011-11-14 | 2012-10-17 | 上海市第一人民医院 | Anti-benign and malignant biliary stricture drug eluting stent and preparation method thereof |
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|---|---|---|---|---|
| US20090269479A1 (en) * | 2008-04-23 | 2009-10-29 | Abbott Cardiovascular Systems Inc. | Method For Biostable Inclusion Of A Biobeneficial Agent On An Outermost Surface Of An Implantable Medical Device |
| US20120015331A1 (en) * | 2009-03-23 | 2012-01-19 | Simon Wood | Scaffold |
| CN102727944A (en) * | 2011-11-14 | 2012-10-17 | 上海市第一人民医院 | Anti-benign and malignant biliary stricture drug eluting stent and preparation method thereof |
| CN102525697A (en) * | 2011-12-22 | 2012-07-04 | 上海纳米技术及应用国家工程研究中心有限公司 | Medicine-carrying membrane-covered stent and preparation method thereof |
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