CN110327494A - A kind of implantation type artificial hepar - Google Patents
A kind of implantation type artificial hepar Download PDFInfo
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- CN110327494A CN110327494A CN201910677038.5A CN201910677038A CN110327494A CN 110327494 A CN110327494 A CN 110327494A CN 201910677038 A CN201910677038 A CN 201910677038A CN 110327494 A CN110327494 A CN 110327494A
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—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
- 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
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
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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
- A61L2420/00—Materials or methods for coatings medical devices
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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/28—Materials or treatment for tissue regeneration for liver reconstruction
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Abstract
The invention discloses a kind of implantation type artificial hepar, the implantation type artificial hepar includes artificial liver bracket and overlay film；The implantation type artificial hepar bracket includes at least one layer of overlay film；The overlay film is duplicature；Implantation type artificial hepar of the present invention is to artificial liver bracket overlay film, with biological correspondence, the biocompatibility of artificial liver can be improved, overlay film can be adsorbed and removed toxin, bacterium in blood etc. simultaneously, the ambient stable for maintaining implantation type artificial hepar promotes transplanted hepatocytess to survive and in patient's body proliferation, regenerating tissues, improves patient's hepatosis, enhance patient body health, improves the quality of living.
Description
Technical field
The present invention relates to regeneration medicine technology field, specially a kind of implantation type artificial hepar.
Background technique
Liver carries the function of the Various Complexes such as synthesis, secretion, metabolism, removing toxic substances as one of most important organ of human body
Can, at present due to the presence of various life stress and disease, inevitably multiple pressure can be brought to liver so that generating lesion, seriously
Even necrosis of liver cells occurs for person, the illnesss such as liver failure occurs, leads to human metabolism function's disorder, in fact it could happen that more serious
Illness, seriously affect health, reduce quality of life.
Artificial liver is by external machinery, and chemical or biological device temporarily or partially substitutes liver function, to assist
Help treatment liver function incomplete or related disease.Artificial liver and the maximum difference of general medicine drug therapy are that the former is main
It is cured the disease by " function replacement ", the latter mainly passes through " function reinforcement " and cures the disease.
Currently, maximally efficient liver failure treatment method be orthotopic liver transplantation, but liver transfer operation one side expense compared with
On the other hand it is less to be adapted to liver source for height, therefore be delayed to the state of an illness of patient extremely serious.Research is dedicated to stem cell people at present
Work is implanted into the patient, and reaches internal proliferation, improves patient's hepatosis problem.It needs during this using artificial liver branch
Frame, but the biocompatibility of the material currently used for artificial liver bracket is poor, and does not have the effect for removing toxin, it is right
Hepatocyte transplantation and internal proliferation have certain limitation.Therefore, a kind of good biocompatibility, and degradable macromolecule material are found
Material, is made the artificial liver bracket that can remove hepatotoxin, has a very important significance.
Chinese patent CN101428154B discloses a kind of implantation type artificial hepar, it includes polyglycolic acid or polylactic acid hydroxyl
Guanidine-acetic acid big envelope, 1 or more three-dimensional porous rack, polyglycolic acid or polylactic-co-glycolic acid channel closure；Three-dimensional porous rack
In polyglycolic acid or polylactic-co-glycolic acid big envelope, polyglycolic acid or polylactic-co-glycolic acid big envelope both ends polyglycolic acid
Or polylactic-co-glycolic acid channel closure.The invention simulates lobuli hepatis structure to greatest extent, promote implantation stem cell directional break up to
Mature hepatocytes, the capilary regeneration of induced tissue engineering liver；It is splendid in three dimensional biological bracket expoeridium biocompatibility simultaneously
Biomaterial big envelope, simulate Glisson's capsule structure, lacunula is formed between the big envelope and bracket, so that blood circulation passes through tissue
Engineering rack promotes in coating the revascularization of engineering liver and ultimately generates artificial liver with substituted host damaged liver function,
But the biocompatibility of implantation type artificial hepar also can further improve.
Chinese patent CN101850136B discloses a kind of connection agents for preparing bioartificial livers bracket, comprising:
Perfusion liquid 1: alkalescent hypotonic solution or pure water；The ionic detergent aqueous solution of 2: one groups of concentration in gradient of perfusion liquid variation；
Perfusion liquid 3: electrolyte aqueous solution；Perfusion liquid 4: anticoagulin aqueous solution；Eluent 1: distilled water；Eluent 2: non-ionic
Detergent aqueous solution.Additionally provide a kind of method for preparing Implantable bioartificial liver with reagent with aforementioned combinations；And one
The Implantable bioartificial liver that kind is prepared in aforementioned manners.Bioartificial livers bracket using connection agents preparation is complete
Decellularization, and extra-cellular matrix structure keeps complete.The bioartificial livers can accommodate a large amount of liver cells and provide sufficient blood
For, it is obviously prolonged the life span of acute hepatic failure rat, liver function is obviously improved, there is fabulous potential applicability in clinical practice,
But the toxin and bacterium in blood are easy to damage implantation type artificial hepar.
Summary of the invention
The present invention against the above deficiency, provides a kind of implantation type artificial hepar, by artificial liver bracket overlay film and suction
The method that attached functional liquid impregnates, solves the problems, such as implantation type artificial hepar poor biocompatibility, cannot remove to blood toxicity.
In order to achieve the goal above, the present invention is achieved by the following technical programs:
A kind of implantation type artificial hepar, implantation type artificial hepar include artificial liver bracket and overlay film；Implanted artificial liver
Ramus splanchnicus frame includes at least one layer of overlay film；Overlay film is duplicature.
Further, chitosan/copolymer of poly lactic acid of the artificial liver bracket by molecular weight by 30,000~90,000 units is made.
Chitosan/copolymer of poly lactic acid is degradable high polymer material, and has certain biocompatibility, will not be made to patient body
At injury, will not be polluted the environment after discarded.
Further, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: press quality for chitosan and polylactic acid
It is mixed than 1:15~30, after chitosan is completely dissolved, by mixture under the conditions of temperature is 75 DEG C~80 DEG C, decompression is de-
It water 3 hours~4 hours, is then heated to 102 DEG C~108 DEG C and continues dehydration 2.1 hours~2.5 hours, it is finally heated to 125 DEG C
~130 DEG C continue dehydration 30 minutes~45 minutes, dehydration after the completion of be added catalyst, under vacuum conditions, temperature be 135 DEG C~
It is reacted 4.0 hours~4.5 hours under the conditions of 145 DEG C, product is dried to obtain the chitosan/copolymer of poly lactic acid by washing.
Further, catalyst is butyl titanate.
Further, catalyst charge is the 1.0%~2.5% of mixture quality.
Further, overlay film is made of the raw material of following parts by weight: 30 parts~40 parts of polycaprolactone, 10 parts of poly (glycolide-lactide)
~16 parts, 3.5 parts~5.5 parts of ossein, 2.6 parts~4.6 parts of tapioca.Overlay film is originally degradation material, including
Ossein can be further improved the biocompatibility and safety in utilization of implantation type artificial hepar.
Further, overlay film is made of the raw material of following parts by weight: 34 parts of polycaprolactone, 13 parts of poly (glycolide-lactide), and bone
4.5 parts of collagen, 3.6 parts of tapioca.
Further, the monofilm thickness of duplicature is 0.02mm~0.05mm.Film can be improved in the overlay film of double-layer structure
Osmotic effect, filtering blood harmful toxins and harmful substance, the survival of protection transplanted hepatocytess and regenerating tissues.
Further, implantation type artificial hepar impregnates 3 minutes~6 minutes in adsorption function liquid.By impregnating, it is being implanted into
Formula artificial liver surface has certain adsorbent, can remove blood toxicity and bacterium, maintains implantation type artificial hepar environment
Stablize, safety.
Further, adsorption function liquid presses quality by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water
It is formed than 0.1~0.3:1.2:1.0:0.5:20~30.
The beneficial effects of the present invention are:
(1) implantation type artificial hepar of the present invention has biological correspondence to artificial liver bracket overlay film, can be improved artificial
The biocompatibility of liver, while overlay film can be adsorbed and removed the toxin etc. in blood, maintain the environment of implantation type artificial hepar
Stablize, promotes transplanted hepatocytess to survive and in patient's body proliferation, regenerating tissues, improve patient's hepatosis, enhance patient
Health is improved the quality of living；
(2) material for the artificial liver bracket and overlay film that the present invention prepares implantation type artificial hepar belongs to degradable material
Material, it is smaller to patient body harm, it is safe to use.
Specific embodiment
In order to enable the purposes, technical schemes and advantages of technical solution of the present invention are clearer, below in conjunction with this
Invention specific embodiment carries out clear, complete description to the technical solution of the embodiment of the present invention.
It should be noted that embodiment of the present invention is only to realize preferred embodiment of the invention, to belonging to this
Invention general idea, and be only obvious change, be within the scope of protection of the invention within.
Embodiment 1
A kind of implantation type artificial hepar
Implantation type artificial hepar includes artificial liver bracket and overlay film；Implantation type artificial hepar bracket includes one layer of overlay film；
Overlay film is duplicature；Artificial liver bracket is made of molecular weight of chitosan/copolymer of poly lactic acid of 30,000 units；Duplicature
Monofilm thickness is 0.02mm；Implantation type artificial hepar impregnates 3 minutes in adsorption function liquid.
Wherein, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: by chitosan and polylactic acid 1:15 in mass ratio
It is mixed, after chitosan is completely dissolved, by mixture under the conditions of temperature is 75 DEG C, decompression dehydration 3 hours, then heats
Continue dehydration 2.1 hours to 102 DEG C, finally heated to 125 DEG C are continued dehydration 30 minutes, and four fourth of metatitanic acid is added after the completion of dehydration
Ester, under vacuum conditions, temperature be 135 DEG C under the conditions of react 4.0 hours, product pass through washing be dried to obtain the chitosan/
Copolymer of poly lactic acid；Wherein, catalyst charge is the 1.0% of mixture quality.
Wherein, overlay film is made of the raw material of following parts by weight: polycaprolactone 30g, poly (glycolide-lactide) 10g, ossein 3.5g,
Tapioca 2.6g.
Wherein, adsorption function liquid is by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water in mass ratio 0.1:
1.2:1.0:0.5:20 composition.
Embodiment 2
A kind of implantation type artificial hepar
Implantation type artificial hepar includes artificial liver bracket and overlay film；Implantation type artificial hepar bracket includes two layers of overlay film；
Overlay film is duplicature；Artificial liver bracket is made of molecular weight of chitosan/copolymer of poly lactic acid of 90,000 units；Duplicature
Monofilm thickness is 0.05mm；Implantation type artificial hepar impregnates 6 minutes in adsorption function liquid.
Wherein, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: by chitosan and polylactic acid 1:30 in mass ratio
It is mixed, after chitosan is completely dissolved, by mixture under the conditions of temperature is 80 DEG C, decompression dehydration 4 hours, then heats
Continue dehydration 2.5 hours to 108 DEG C, finally heated to 130 DEG C are continued dehydration 45 minutes, and four fourth of metatitanic acid is added after the completion of dehydration
Ester, under vacuum conditions, temperature be 145 DEG C under the conditions of react 4.5 hours, product pass through washing be dried to obtain the chitosan/
Copolymer of poly lactic acid；Wherein, catalyst charge is the 2.5% of mixture quality.
Wherein, overlay film is made of the raw material of following parts by weight: polycaprolactone 40g, poly (glycolide-lactide) 16g, ossein 5.5g,
Tapioca 4.6g.
Wherein, adsorption function liquid is by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water in mass ratio 0.3:
1.2:1.0:0.5:30 composition.
Embodiment 3
A kind of implantation type artificial hepar
Implantation type artificial hepar includes artificial liver bracket and overlay film；Implantation type artificial hepar includes three layers of overlay film；Overlay film
For duplicature；Artificial liver bracket is made of molecular weight of chitosan/copolymer of poly lactic acid of 40,000 units；The single layer of duplicature
Film thickness is 0.03mm；Implantation type artificial hepar impregnates 4 minutes in adsorption function liquid.
Wherein, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: by chitosan and polylactic acid 1:16 in mass ratio
Be mixed, after chitosan is completely dissolved, by mixture temperature be 76 DEG C under the conditions of, decompression dehydration 3.2 hours, then plus
Heat continues dehydration 2.2 hours to 103 DEG C, and finally heated to 126 DEG C are continued dehydration 35 minutes, and four fourth of metatitanic acid is added after the completion of dehydration
Ester, under vacuum conditions, temperature be 137 DEG C under the conditions of react 4.1 hours, product pass through washing be dried to obtain the chitosan/
Copolymer of poly lactic acid；Wherein, catalyst charge is the 1.2% of mixture quality.
Wherein, overlay film is made of the raw material of following parts by weight: polycaprolactone 32g, poly (glycolide-lactide) 11g, ossein 4.0g,
Tapioca 3.2g.
Wherein, adsorption function liquid is by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water in mass ratio 0.3:
1.2:1.0:0.5:22 composition.
Embodiment 4
A kind of implantation type artificial hepar
Implantation type artificial hepar includes artificial liver bracket and overlay film；Implantation type artificial hepar includes one layer of overlay film；Overlay film
For duplicature；Artificial liver bracket is made of molecular weight of chitosan/copolymer of poly lactic acid of 80,000 units；The single layer of duplicature
Film thickness is 0.04mm；Implantation type artificial hepar impregnates 5 minutes in adsorption function liquid.
Wherein, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: by chitosan and polylactic acid 1:25 in mass ratio
Be mixed, after chitosan is completely dissolved, by mixture temperature be 79 DEG C under the conditions of, decompression dehydration 3.8 hours, then plus
Heat continues dehydration 2.4 hours to 106 DEG C, and finally heated to 129 DEG C are continued dehydration 42 minutes, and four fourth of metatitanic acid is added after the completion of dehydration
Ester, under vacuum conditions, temperature be 142 DEG C under the conditions of react 4.4 hours, product pass through washing be dried to obtain the chitosan/
Copolymer of poly lactic acid；Wherein, catalyst charge is the 2.3% of mixture quality.
Wherein, overlay film is made of the raw material of following parts by weight: polycaprolactone 38g, poly (glycolide-lactide) 15g, ossein 5.0g,
Tapioca 4.2g.
Wherein, adsorption function liquid is by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water in mass ratio 0.1:
1.2:1.0:0.5:28 composition.
Embodiment 5
A kind of implantation type artificial hepar
Implantation type artificial hepar includes artificial liver bracket and overlay film；Implantation type artificial hepar includes one layer of overlay film；Overlay film
For duplicature；Artificial liver bracket is made of molecular weight of chitosan/copolymer of poly lactic acid of 70,000 units；The single layer of duplicature
Film thickness is 0.04mm；Implantation type artificial hepar impregnates 5 minutes in adsorption function liquid.
Wherein, modification of chitosan/copolymer of poly lactic acid is the preparation method comprises the following steps: by chitosan and polylactic acid 1:20 in mass ratio
Be mixed, after chitosan is completely dissolved, by mixture temperature be 78 DEG C under the conditions of, decompression dehydration 3.5 hours, then plus
Heat continues dehydration 2.3 hours to 105 DEG C, and finally heated to 128 DEG C are continued dehydration 40 minutes, and four fourth of metatitanic acid is added after the completion of dehydration
Ester, under vacuum conditions, temperature be 140 DEG C under the conditions of react 4.3 hours, product pass through washing be dried to obtain the chitosan/
Copolymer of poly lactic acid；Wherein, catalyst charge is the 2.0% of mixture quality.
Wherein, overlay film is made of the raw material of following parts by weight: polycaprolactone 34g, poly (glycolide-lactide) 13g, ossein 4.5g,
Tapioca 3.6g.
Wherein, adsorption function liquid is by porous adsorbing material, acrylic acid, n-butanol, beta-cyclodextrin and water in mass ratio 0.2:
1.2:1.0:0.5:25 composition.
These are only the preferred embodiment of the present invention, is not intended to restrict the invention, for those skilled in the art
For member, the invention may be variously modified and varied.All within the spirits and principles of the present invention, it is made it is any modification,
Equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of implantation type artificial hepar, which is characterized in that the implantation type artificial hepar includes artificial liver bracket and overlay film；
The implantation type artificial hepar bracket includes at least one layer of overlay film；The overlay film is duplicature.
2. implantation type artificial hepar according to claim 1, which is characterized in that the artificial liver bracket is by molecular weight
Chitosan/copolymer of poly lactic acid of 30000~90,000 units is made.
3. implantation type artificial hepar according to claim 2, which is characterized in that the modification of chitosan/polylactic acid copolymerization
Object the preparation method comprises the following steps: chitosan and polylactic acid 1:15 in mass ratio~30 are mixed, will after chitosan is completely dissolved
Mixture temperature be 75 DEG C~80 DEG C under the conditions of, decompression dehydration 3 hours~4 hours, be then heated to 102 DEG C~108 DEG C after
Continuous dehydration 2.1 hours~2.5 hours, finally heated to 125 DEG C~130 DEG C are continued dehydration 30 minutes~45 minutes, and dehydration is completed
After catalyst is added, under vacuum conditions, temperature be 135 DEG C~145 DEG C under the conditions of react 4.0 hours~4.5 hours, product pass through
It crosses washing and is dried to obtain the chitosan/copolymer of poly lactic acid.
4. implantation type artificial hepar according to claim 3, which is characterized in that the catalyst is butyl titanate.
5. implantation type artificial hepar according to claim 3, which is characterized in that the catalyst charge is compounding substances
The 1.0%~2.5% of amount.
6. implantation type artificial hepar according to claim 1, which is characterized in that the overlay film by following parts by weight raw material
Composition: 30 parts~40 parts of polycaprolactone, 10 parts~16 parts of poly (glycolide-lactide), 3.5 parts~5.5 parts of ossein, 2.6 parts of tapioca
~4.6 parts.
7. implantation type artificial hepar according to claim 6, which is characterized in that the overlay film by following parts by weight raw material
Composition: 34 parts of polycaprolactone, 13 parts of poly (glycolide-lactide), 4.5 parts of ossein, 3.6 parts of tapioca.
8. implantation type artificial hepar according to claim 1, which is characterized in that the monofilm thickness of the duplicature is
0.02mm~0.05mm.
9. implantation type artificial hepar according to claim 1, which is characterized in that the implantation type artificial hepar is in absorption function
It can be impregnated 3 minutes~6 minutes in liquid.
10. implantation type artificial hepar according to claim 9, which is characterized in that the adsorption function liquid is by porous absorption
Material, acrylic acid, n-butanol, beta-cyclodextrin and water 0.1~0.3:1.2:1.0:0.5:20 in mass ratio~30 composition.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111840637A (en) * | 2020-05-08 | 2020-10-30 | 陈艳 | Material for artificial liver and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111840637A (en) * | 2020-05-08 | 2020-10-30 | 陈艳 | Material for artificial liver and preparation method thereof |
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