CN107811669B - Microtubular for ganglioside GM_3 operation - Google Patents
Microtubular for ganglioside GM_3 operation Download PDFInfo
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- CN107811669B CN107811669B CN201711197379.XA CN201711197379A CN107811669B CN 107811669 B CN107811669 B CN 107811669B CN 201711197379 A CN201711197379 A CN 201711197379A CN 107811669 B CN107811669 B CN 107811669B
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- microtubular
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- PFJKOHUKELZMLE-VEUXDRLPSA-N ganglioside GM3 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@@H]([C@H](O)/C=C/CCCCCCCCCCCCC)NC(=O)CCCCCCCCCCCCC\C=C/CCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O1 PFJKOHUKELZMLE-VEUXDRLPSA-N 0.000 title claims abstract description 5
- 239000007788 liquid Substances 0.000 claims abstract description 39
- 229920000642 polymer Polymers 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 239000000829 suppository Substances 0.000 claims abstract description 12
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 230000002093 peripheral effect Effects 0.000 claims abstract description 7
- 238000007711 solidification Methods 0.000 claims abstract description 6
- 230000008023 solidification Effects 0.000 claims abstract description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 44
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 claims description 15
- UFRKOOWSQGXVKV-UHFFFAOYSA-N ethene;ethenol Chemical compound C=C.OC=C UFRKOOWSQGXVKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000004715 ethylene vinyl alcohol Substances 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 10
- 229910000510 noble metal Inorganic materials 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000013461 design Methods 0.000 claims description 4
- 239000004698 Polyethylene Substances 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- -1 polyethylene Polymers 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- 239000012046 mixed solvent Substances 0.000 claims 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims 2
- 229910001080 W alloy Inorganic materials 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 1
- ZONODCCBXBRQEZ-UHFFFAOYSA-N platinum tungsten Chemical compound [W].[Pt] ZONODCCBXBRQEZ-UHFFFAOYSA-N 0.000 claims 1
- 150000004040 pyrrolidinones Chemical class 0.000 claims 1
- 230000003252 repetitive effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 24
- 238000005516 engineering process Methods 0.000 abstract description 13
- 201000008450 Intracranial aneurysm Diseases 0.000 abstract description 7
- 235000007164 Oryza sativa Nutrition 0.000 abstract description 3
- 235000012149 noodles Nutrition 0.000 abstract description 3
- 235000009566 rice Nutrition 0.000 abstract description 3
- 240000007594 Oryza sativa Species 0.000 abstract 1
- 239000012071 phase Substances 0.000 description 20
- 239000012530 fluid Substances 0.000 description 15
- 206010002329 Aneurysm Diseases 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 9
- 239000000835 fiber Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 208000005189 Embolism Diseases 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 210000001367 artery Anatomy 0.000 description 7
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 3
- 230000003073 embolic effect Effects 0.000 description 3
- 239000003292 glue Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 241000209094 Oryza Species 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229920001038 ethylene copolymer Polymers 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 2
- 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 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=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](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 239000011806 microball Substances 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000003294 onyx copolymer Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 201000009371 venous hemangioma Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
- A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
- A61B17/12113—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel within an aneurysm
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
- A61B17/12181—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
- A61B2090/3966—Radiopaque markers visible in an X-ray image
Abstract
The present invention relates to a kind of microtubulars for ganglioside GM_3 operation, the microtubular includes at least the central passage and peripheral channel of coaxial arrangement, central passage is can developer liquids suppository access, peripheral channel is the aqueous solution channel for having viscosity, can spiralization and solidification of the developer liquids suppository in microtubular with realization.The technology combines microflow control technique, liquid embolizing agent technology and microtubular technology, which can realize that liquid embolizing agent in solidifying in microtubular, forms the filling " polymer springs circle " of spiral rice noodles shape developed.The polymer " spring ring " can be applied to intracranial aneurysm filling operation.
Description
Technical field
The present invention relates to ganglioside GM_3 field of surgical, more specifically to a kind of by microflow control technique, liquid bolt
The new technology that suppository technology and microtubular technology combine, the technology can realize liquid embolizing agent in solidifying in microtubular, shape
At the filling " polymer springs circle " of spiral rice noodles shape developed.
Background technique
Due to mechanical damage, vascular sclerosis, hypertension, the hyperplasia of vascular smooth muscle cells, bacterium or virus infection, vein
The effect of the internal and external factors such as the induction of valve disease or blood flow impact, will form hemangioma in artery and vein vascular.Hemangioma is divided into
Aneurysm and phlebangioma, wherein generate the aneurysm with boss wall in encephalic, be referred to as cerebral aneurysm.Arteriae cerebri
Tumor easily induces subarachnoid hemorrhage in rupture, so as to cause sufferer apoplexy；Even, 80% or more patient recurring
It can be dead after cerebral aneurysm rupture.Therefore, embolism or envelope are carried out in the earlier stage that cerebral aneurysm occurs as far as possible
It is stifled to become optimal healing means.
In the method for embolism cerebral aneurysm, generally the aneurysm formed is blocked using surgical operation,
Including clamping aneurysm neck for the cutting of aneurysm mother artery, ligation and using aneurysm clip, to block blood to dynamic
The impact of arteries and veins tumor.But this method takes a long time and is likely to cause aneurysmal breakage.In recent years, with blood vessel image
Development, using intervention operation method, by various embolism materials being delivered in cerebral aneurysm to block, embolism artery
Tumor is gradually instead of traditional surgical operation.However, thrombosis rate using the method for noble metal spring ring is lower, is easy shape
Cause cerebrum block at large-scale thrombus etc..And usually, an aneurysm filling operation, averagely needs 4-5
Spring ring.Spring ring expense is tens of thousands of tens of thousands of to be differed to ten.One huge burden is undoubtedly for patient and patient family.
Multiple intra-arterial tumor choke material has been disclosed at present, be broadly divided into solid embolism materials such as noble metal spring ring and
Two class of liquid embolic material.Liquid embolic material can be directly injected into that aneurysm tumor is intracavitary, adapt to the dynamic of different shape and size
Arteries and veins tumor chamber makes not staying any gap between tumor wall and embolism materials, to reach permanent occlusion.Such as the Onyx of EV3 Company
HD500 is exactly a liquid embolizing agent specifically for aneurysm filling.Onyx glue composition is very simple, it is gathered by polyvinyl alcohol
Ethylene copolymer EVOH, dimethyl sulfoxide DMSO solvent and the Ta powder used Ta composition of micron.Wherein Onyx18 and Onyx34 is dynamic in brain
It is commonly used in the embolism of venous malformation (AVM).Because it allows doctor to inject for a long time, with better dispersivity and more
High thrombosis rate, autography, and have the characteristics that non-adhering.However Onyx HD500 is applied to the liquid of intracranial aneurysm filling
Body embolism materials are cumbersome but because it is using complexity.It needs to be protected with tumor mouth of the sacculus to parent artery, prevents liquid
Body glue is gone to outside aneurysm.And want multiple full and contraction operation.Nonetheless still it is possible to there can be liquid glue race
Aneurysmal dangerous generation out.So this product has stopped selling substantially.
Micro-fluidic (Microfluidics) is referred to using microchannel (having a size of tens of to hundreds of microns) processing or manipulation
Science and Technology involved in the system of minute fluid (volume be nanoliter arrive A Sheng) is one and is related to chemistry, fluid physics, micro-
The emerging cross discipline of electronics, new material, biology and biomedical engineering.Micro-fluidic important feature first is that minute yardstick ring
There are unique fluid properties, such as laminar flow and drop under border.It is micro-fluidic to may be implemented one by these unique fluid phenomenons
Serial conventional method is difficult to the micro Process and microoperation completed.Main fluid phenomenon has drop and laminar flow.
1, the drop of microflow control technique
When the immiscible liquid of two-phase (You Heshui) flows in microfluidic channel, in liquid/liquid interface tension and shearing
Under the action of power, wherein one phase flow is known from experience to form highly homogeneous cutout, i.e. drop.In the method for lotion preparation, if
It says that the method based on stirring is top-down, is bottom-to-top method then micro-fluidic.It is micro-fluidic can be with very high
Flux preparation high degree of monodispersity drop lotion.Common microchannel structure is T-type and ψ type.In some cases, contain
The aqueous phase liquid of different high molecular polymers also will form immiscible drop in microfluidic channel.Based on this method, China
The Liu Shanshan et al. of middle University of Science and Technology is prepared for interventional therapy autography blood vessel embolism polymer microballoon.They are with sodium alginate
Aqueous solution is dispersed phase, to contain generated in-situ CaCl2The atoleine of nanoparticle is continuous phase, micro-fluidic based on drop type
Technology combination precrosslink method, has been made the calcium alginate gel bead of size tunable and monodisperse, good sphericity.Method can pass through
Change the velocity ratio of micro fluidic device construction size and continuous phase and dispersed phase, regulates and controls gel micro-ball size at 40 μm~700 μm
Between.Obtained microspherulite diameter distribution is uniform, and has good X-ray developability.
2, the laminar flow of microflow control technique
Laminar flow is corresponding with turbulent flow, refers to the laminar flow of fluid, and streamline is parallel to each other with tube wall.Viscous force much
When greater than inertia force or Reynolds number (Reynold number) less than 3000, laminar flow just will appear.When the stream of a few phase different colours
When body enters the same microchannel from different entrances, even if they dissolve each other, well-bedded multiphase PARALLEL FLOW also will form.
Using this geometry regularity of laminar flow, the ordered arrangement of material, chemical environment and cell in microchannel may be implemented.
Summary of the invention
The present invention has following technical essential and element:
This is two-piece design for the microtubular of neural interventional treatment.As shown in figure 3, its proximal segment has annula
Structure has exocoel 3-1 and inner cavity 3-2.And be single cavity body structure in distal ports, " spring ring (3-3) can this section again for polymer
Solidification or spiralization.
It forms visible " polymer springs circle " the inner cavity solution of X development and is necessary for the liquid embolic that itself there is developability
Agent.
Exocoel solution is the aqueous solution for having some shear viscosities, exocoel solution and inner cavity solution in distal end single-chamber section forming layer
Fluid is flowed, and solidifies the liquid embolizing agent of inner cavity solution gradually.
There is proximal segment annula structure to be rule of thumb preferably designed for exocoel (1-1 and 4-1) and be square structure,
It is preferred that inner cavity (1-2 and 4-2) is circular configuration.As shown in Figure 1 and Figure 4.
The present invention combines microflow control technique, liquid embolizing agent technology and microtubular technology, and preferred liquid suppository is
Can developer liquids suppository, more preferable non-sticky can developer liquids suppository.It is thus achieved that by liquid embolizing agent direct transformation
Develop visible " polymer springs circle " for X.Closely packed filling can be realized for intracranial aneurysm by being somebody's turn to do " polymer springs circle ".
It can stop the injection of inner cavity solution at any time during filling, retain the injection flow velocity of exocoel solution, realize similar
Noble metal spring ring frees process.Easy to operate, process control is good.
Detailed description of the invention
Present invention will be further explained below with reference to the attached drawings and examples, in attached drawing:
Fig. 1, microtubular cross-sectional；
Fig. 2: micro-fluidic longitudal section photo；
Fig. 3: microtubular longitudal section and " polymer springs circle " form schematic diagram；
Fig. 4 microfluidic control is for coiling-type polymer " spring ring " schematic diagram；
Fig. 5: polymer " spring ring " microscope photo.
Specific embodiment
Below in conjunction with the specific embodiment of specific embodiment
Above content of the invention is described in further detail.
The present invention is based on micro-fluidic laminar fluid form, and liquid embolizing agent technology is combined in it.As a result, may be used
To form " the polymer springs circle " of a kind of injectable.We are for microtubular structure, according to micro-fluidic forming layer manifold state institute
The feature needed is designed, and the microtubular of the design has two-way feed pathway (exocoel inner cavity double cavity structure): central circular channel
For liquid embolizing agent access, peripheral square duct is the aqueous solution channel (please referring to Fig. 2) for having viscosity.The cross-sectional view of structure is such as
Shown in Fig. 1.
Can developer liquids suppository can by polyvinyl alcohol polyethylene and ethylene copolymers (EVOH), dimethyl sulfoxide (DMSO) solvent and
The Ta powder used composition of micron.Tantalum powder is developer, can also be other noble metal micron powders.Polymer EVOH is dissolved in DMSO
In, but it is not dissolved in water.So polymer will be from DMSO solvent when the DMSO solution of EVOH encounters water or blood
In be precipitated out.Ta powder can be embedded in the colloidal condensate of its formation by polymer EVOH precipitation process.Because it has embedded Ta
Powder, so it can develop under X-ray.Liquid embolizing agent is by will gradually be cured as polymer in the microtubular
Rice noodles shape " filling spring ring ".And we can allow it to come out in microtubular by adjusting the length of the laminar flow section of microtubular
Sufficiently solidify when in into human body artery tumor.After aneurysm filling is complete, doctor need to only stop bore passages solution
Injection, and retain the solution injection in exocoel channel.This process, that is, visual frees process for spring ring.By this process,
The i.e. available liquid embolizing agent of doctor, which is formed by before " polymer springs circle " reaches, clogs multiple noble metal spring rings
Effect.And filling is finer and close, process is more reliable.And the financial burden of patient can be largely reduced, because of " polymer
The cost of spring ring " is far below noble metal spring ring.
In addition, this is two-piece design for the microtubular of neural interventional treatment.As shown in figure 3, its proximal segment has together
Axis double cavity structure has exocoel 3-1 and inner cavity 3-2.And be single cavity body structure in distal ports, " spring ring (3-3) can be again for polymer
The solidification of this section or spiralization.
Below to example is enumerated, further specifically described to of the invention.1, experimental raw and reagent
Polyvinylpyrrolidone (Mn=500,0g/mol analyze pure, Sinopharm Chemical Reagent Co., Ltd.)；Diformazan is sub-
Sulfone (DMSO analyzes pure, Sinopharm Chemical Reagent Co., Ltd.)；Polyethylene glycol (PEG400, Mn=400g/mol, analysis is pure,
Sinopharm Chemical Reagent Co., Ltd.)；Ta powder (micron-nanometer grade) (Ningxia east tantalum industry)；EVOH polymer (Taiwan Changchun
Company)
2, micro fluidic device is built
Single emulsion capillary micro fluidic device is built: two round tubes are inserted into square tube, Cheng Yi from the two sides of square tube respectively
It is arranged in a straight line, and the pipe after assembling is fixed on glass slide.As shown in figure 4, the round tube in left side is as interior phase channel, square tube
Left side is as foreign minister channel, and the round tube on right side is as one section of collecting region (4-3).The internal diameter and outer diameter of round tube are 600 μm respectively
And 1.0mm, the internal diameter of square tube are 1.0mm.Diameter is truncated to 30 μm after drawing needle device to burn carefully, then by burning needle device by the end of inlet tube
Left and right.The end that one section of collecting region connects two sections of collecting region (4-4) bigger (polytetrafluoroethyl-nes with different inner diameters of an internal diameter
The square tube that alkene pipe either internal diameter is 1mm).
As shown in figure 4, the mixed solution of EVOH/DMSO/Ta powder and PEG aqueous solution are mixed as interior phase and outside
Liquid.Two-phase in the internal and external channel by syringe pump injection micro fluidic device, forms two parallel streams respectively in one section of collecting region
Body.Then two parallel fluids enter two sections of a broader collecting region, are spontaneously generated screw type in two Duan Zhonghui of collecting region
Fiber.Wherein, in figure dj be initial fluid diameter；Df is the diameter for the solid fiber being collected into；D1 is the internal diameter of capillary；
The internal diameter that d2 is two sections of collecting region；λ is the wavelength of helically oriented fiber, and l is between one section of end of import pipe end and collecting region
Distance.In this process, after dispersed phase enters one section of collecting region, the DMSO in fluid starts to move to continuous phase liquid PEG phase
It moves.With the migration of DMSO, the viscosity of internal phase fluid increases, and starts to shrink.This will lead to the accumulation of elastic energy and stress,
It can only can be discharged by folding.Meanwhile channel broadens interior foreign minister is caused to generate speed difference, this can generate internal phase fluid
Viscous drag, so as to cause curling.In addition, as the DMSO in the mixed solution of EVOH/DMSO/Ta powder is quickly to liquid PEG
It is spread in phase, interior phase liquid can gradually solidify, and the shape of spiral will be maintained after solidification.Straight fluid/fiber is changed into screw type
Fiber is broadened caused by the synergistic effect of (collecting region one section to collecting region two sections) from the water of interior phase to foreign minister's migration and channel.
It should be noted that this and before be based on two-phase aqueous systems, microfluidic control for the report of microballoon or microfibre difference.At these
In report, their aqueous solution for being PEG and Quick cross-linking in situ realize solidification.
By flow velocity, l value and the concentration of EVOH/DMSO solution etc. for simply adjusting interior foreign minister, not similar shape can be made
The fiber of looks, the fiber including screw type, wavy and unordered curling.For all these fibers, df/djControl is 0.5
Left and right (table 1).Illustrate in this preparation process, due to the diffusion of water, the diameter of liquid embolizing agent phase reduces~50%.Cause
This, we can adjust the initial diameter of fluid simply by the flow velocity of foreign minister in changing, to control final fiber
Diameter (table 1).
Embodiment 1-4 is as shown in table 1:
Influence of foreign minister's flow velocity to dj, df and df/dj in table 1
Embodiment 5, Qin=200 μ L/h, Qout=5mL/h, d1=600 μm, EVOH/DMSO=6wt%), l=3cm dress
It sets.
Embodiment 6, Qin=200 μ L/h, Qout=5mL/h, d1=600 μm, EVOH/DMSO=6wt%), l=6cm dress
It sets.
Embodiment 7, Qin=200 μ L/h, Qout=5mL/h, d1=600 μm, EVOH/DMSO=6wt%), l=9cm dress
It sets.
Embodiment 8, Qin=200 μ L/h, Qout=5mL/h, d1=600 μm, EVOH/DMSO=8wt%), l=9cm dress
It sets.
Embodiment 9, Qin=200 μ L/h, Qout=5mL/h, d1=600 μm, EVOH/DMSO=10wt%), l=9cm dress
It sets.
By above embodiments, micro-fluidic obtained polymer " spring ring " is as shown in Figure 5.1-9 respectively correspond 5-a
To 5-i.
Claims (7)
1. a kind of microtubular for ganglioside GM_3 operation, which is characterized in that the microtubular includes at least in coaxial arrangement
Heart channel and peripheral channel, central passage be can developer liquids suppository access, peripheral channel is the aqueous solution channel for having viscosity,
It can spiralization and solidification of the developer liquids suppository in microtubular with realization.
2. microtubular according to claim 1, it is characterised in that: the microtubular divides two-piece design, and proximal segment is formed
The central passage and peripheral channel, and the peripheral channel is square structure, central passage is circular configuration；And distal ports are
Single lumen catheter structure.
3. microtubular according to claim 1, it is characterised in that: it is described can developer liquids suppository include at least water it is insoluble
The polymer of solution, can the corresponding solvent of developer liquids suppository and micronized three ingredients of noble metal powder.
4. microtubular according to claim 3, it is characterised in that: also contain polyethylene-polyethylene in the liquid embolizing agent
The copolymer EVOH of alcohol repetitive unit.
5. microtubular according to claim 3, it is characterised in that: the solvent is N-Methyl pyrrolidone or N-
The mixed solvent of the mixed solvent or N-Methyl pyrrolidone of methyl pyrrolidone and DMSO, DMSO and dehydrated alcohol, or
Person is the mixed solvent of N-Methyl pyrrolidone and dehydrated alcohol.
6. microtubular according to claim 3, it is characterised in that: it is described can developer liquids suppository further include development
Agent, the developer are the micronized platinum powder of micronized ta powder or micronized platinum-tungsten alloys powder
End.
7. microtubular according to claim 1, it is characterised in that: the aqueous solution is polyethylene glycol PEG either polyethylene
The aqueous solution of base pyrrolidones PVP.
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