CN107822744A - A kind of preparation method for the tip composite particles for improving union - Google Patents

A kind of preparation method for the tip composite particles for improving union Download PDF

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Publication number
CN107822744A
CN107822744A CN201711021081.3A CN201711021081A CN107822744A CN 107822744 A CN107822744 A CN 107822744A CN 201711021081 A CN201711021081 A CN 201711021081A CN 107822744 A CN107822744 A CN 107822744A
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China
Prior art keywords
composite particles
medicine
preparation
layer
model
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CN201711021081.3A
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Chinese (zh)
Inventor
王全宝
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Xishan District Donggang Xiaoming Electronic Product Management Department
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Xishan District Donggang Xiaoming Electronic Product Management Department
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Priority to CN201711021081.3A priority Critical patent/CN107822744A/en
Publication of CN107822744A publication Critical patent/CN107822744A/en
Withdrawn legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • A61F2/30942Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2835Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006Properties of materials and coating materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389The prosthesis being coated or covered with a particular material

Abstract

The present invention provides a kind of preparation method for the tip composite particles for improving union, comprises the following steps:1)It is " U " font and the model being coincide with fracture line section to make drift angle section in advance;2)Elastic layer, the medicine layer of moistening are made respectively, the elastic layer is fine and close degradable or nondegradable biomembrane, medicine layer material be and the good degraded or non-degradable of human body bone bio-compatible, absorb do not absorb either or porosity and looseness material, be also encapsulated with the medicine for having facilitation to sclerotin healing inside medicine layer;3)The elastic layer of moistening is covered on model vertex, model vertex is wrapped and extends to model vertex both sides, then the medicine layer of moistening is covered on elastic layer, forms biological microstructure film;4)Biological microstructure film is carried out to the detachment of width on demand;5)After air-drying shape fixation Deng composite particles, the composite particles made are peeled off from model vertex.

Description

A kind of preparation method for the tip composite particles for improving union
Technical field
Present invention relates to a kind of preparation method for the tip composite particles for improving union.
Background technology
It is attached to currently with the biological composite membrane comprising growth factor/stem cell at fracture line, to strengthen union Speed and quality, it has been the Disciplinary Frontiers of medical research.Fracture line(Concordant profipole)Blood vessel, osteocyte etc. is distributed with inner surface, Whether healing is good, depending on blood vessel, the growing state of osteocyte in fracture anastomosis line.Biomembrane is fitted in fracture anastomosis line Why surface can increase the quality of union, and its reason is the medicine of one side biomembrane encapsulated inside to fracture anastomosis The growth of blood vessel, osteocyte in line has a facilitation, and another aspect biomembrane is by tissue and fracture such as the muscle in the external world Concordant profipole is isolated, and prevents reaction of the tissue to blood vessel, bone cell growth in fracture anastomosis line.Therefore, it is biological Facilitation of the film to union, it should be embodied in and effective medicine and the isolation external world are applied with to fracture anastomosis line inner surface The tissue such as muscle.
The way of contact of existing biological composite membrane and fracture line is often by the way of being directly bonded, but this kind of mode Bring problems with:
1, biological composite membrane bulk area is bigger, and fracture area is smaller, and 2 can not effectively be bonded and be fixed on one Rise.
2, the limitation of current biological composite membrane material and manufacture craft, cause the degradation speed of biological composite membrane, carry Growth factor release active drug concentration time(The valid density duration is the key of fracture line healing quality) It can not be met clinical needs etc. performance indications.See《Growth factor slow-release system promotes the experimental study of fracture of mandible healing》; 《Growth factor/collagem membrane slow-released system promotes the research of union》.
Therefore, on the basis of existing biological composite membrane manufacture craft, new structure of composite membrane, and newly compound are explored The fitting of film and fracture line and fixed form, strengthen the speed and quality of union, into the direction of scientific and technical personnel's innovation.
The content of the invention
A kind of preparation method for the tip composite particles for improving union, comprises the following steps:
1)It is " U " font and the model being coincide with fracture line section to make drift angle section in advance;
2)Elastic layer, the medicine layer of moistening are made respectively, the elastic layer is fine and close degradable or nondegradable biomembrane, Medicine layer material be and the good degraded or non-degradable of human body bone bio-compatible, absorb do not absorb either or it is porous Unconsolidated material, the medicine for having facilitation to sclerotin healing is also encapsulated with inside medicine layer;
3)The elastic layer of moistening is covered on model vertex, model vertex is wrapped and extends to model vertex both sides, then The medicine layer of moistening is covered on elastic layer, forms biological microstructure film;
4)Biological microstructure film is carried out to the detachment of width on demand;
5)After air-drying shape fixation Deng composite particles, the composite particles made are peeled off from model vertex.
Wax and elastic layer material are immiscible from each other, are easy to peel off from wax pattern after air-drying.
Further, fracture line section after in vitro people's bone artificial fracture with being made.The different people in fracture line section It is all similar.Therefore fracture line section after in vitro people's bone artificial fracture with being made.
Further, drift angle section is " U " font and the model identical with fracture line section is cast on fracture line with wax, Then wax solidification is waited to be formed model later.Wax and sclerotin are also immiscible, drift angle section be " U " font and with fracture line section Identical model is cast on fracture line with wax, then waits wax solidification to be formed model later, the model is easy to from fracture Taken off on line.
Further, biological microstructure film periphery is can not permeate the medical bio of the stimulate neuronal growth factor and stem cell Glue is closed.
Further, the elastic layer material is in PLA, collagen, fibrin, biogel, poly butyric ester One or several kinds of mixtures.
Further, the elastic layer material is that can not permeate the medical bio of the stimulate neuronal growth factor and stem cell Glue.
Further, medicine Rotating fields are and human body bone bio-compatible good fiber shape or areolation.
Further, the material of medicine layer is using the material for having facilitation after degraded to bone cell growth.
Further, medicine layer material is that either cellulose or biogel or sterilization or disappear at algal gel azelon Cytotoxic activity charcoal.
Further, the combination of growth factor either stem cell or growth factor and stem cell is encapsulated with medicine layer.
Further, medicine layer is encapsulated with degradable medicaments slow-released system.
On the structure and material inside each layer of biomembrane, in biomembrane related paper and patent document, discuss That states is perfectly clear, such as 201510716279.8 a kind of composite repairing materials for being used to bridge defect nerve and its support, 201480055424.6 compositions and delivery system, 201280027492.2 are for regenerative medicine and for tissue supports Bio-compatible and biodegradable gradient layer system.Section is in " U " font word after the application is characterised by its folding Type.The requirement for carrying medicine and delivery system that structure and material inside each layer are bonded together in satisfaction in the form of biological composite membrane Under, the various structures and material that provide can be selected in above paper and patent document.
Due to the limitation of biomembrane manufacture craft, the biomembrane one side volume of whole is larger, on the other hand real and bone The area for rolling over the contact of concordant profipole inner surface depends on the area of fracture anastomosis line inner surface.So only and fracture anastomosis line in table Medicine on the biomembrane in that block region of face contact can just contact fracture anastomosis line inner surface.Therefore, the application really needs The technical problem of solution is:
First, how in biomembrane manufacture craft(Each Rotating fields and material)On the Process ba- sis not improved further, fracturing In the case that concordant profipole inner surface area is constant, the concentration of increase biomembrane release medicine and time;
Second, how preferably biomembrane to be bonded and is fixed on fracture anastomosis line;
Third, how preferably the tissues such as the muscle in the external world and fracture anastomosis line inner surface to be mutually isolated.
For first problem, after fracture operation, fracture anastomosis line(Between between the knochenbruch surface being stitched together Gap)Formation cross-section is " U " trench structure.It is now biological if being directly bonded horizontal biomembrane on the trench structure Film and the area of fracture anastomosis line inner surface contact are only:The length of the width * trench structures of " U " trench structure upper surface.Such as Fruit fills in the biomembrane that section itself is also " U " in the trench structure inner surface, then now biomembrane and fracture anastomosis line The area of inner surface contact is at least:The length * 2 of the depth * trench structures of " U " trench structure." on ' U ' type trench structure When the width on surface " and " depth of ' U ' type trench structure " ratio are close to " 1 ", now obvious 2nd kind of biofilm structure can be Biomembrane manufacture craft(Each Rotating fields and material)On the Process ba- sis not improved further, in fracture anastomosis line inner surface face In the case that product is constant, increase biomembrane and the area of fracture anastomosis line inner surface contact.
For Second Problem, later composite biological film is folded, because its internal layer is elastic layer, outer layer is weaker zone (Medicine layer), therefore later " U " structure is folded, by the elastic reaction of internal layer elastic layer(Elastic layer material is fine and close, fold with After produce restoring force), itself has the trend expanded to both sides.Elastic force caused by certain elastic layer is very little, but It is enough inner surface of the edge " compression " at left and right sides of the top composite biological film " U " structure in fracture anastomosis line both sides.
For the 3rd problem, principle is same as above, because the edge " compression " at left and right sides of composite biological film top is being fractured The inner surface of concordant profipole both sides, hence in so that the tissue such as fracture anastomosis line inner surface and outside muscle obtain effectively every From.
Simultaneously as the elastic layer material is that can not permeate the Medical Living Creature Gum of growth factor, therefore medicine layer is encapsulated Medicine, can only be to inner side(Fracture anastomosis line inner surface)Release, can not discharge laterally(The human body tissue sides such as muscle)So that Limited entrapped drug(One of biomembrane process bottleneck is exactly the amount of entrapped drug can not be too many)Can be with targeted release to fracture Concordant profipole inner surface, reach the purpose precisely treated.
The most important purposes of the biologic grain, it is the gap for clogging the fracture anastomosis line end.The biologic grain small volume, can To clog the gap of the fracture anastomosis line end.
What is required emphasis is a little that the application uses outer layer as weaker zone(Medicine layer)It is direct with fracture anastomosis line inner surface The mode of contact, brings a performance more superior than traditional biological film laminating type, i.e. weaker zone can draw in bony surface Lead osteocyte to grow in the material of porosity and looseness, new osteocyte can also obtain entrapped drug in weaker zone in production process Effective nourishing and promotion.As for porosity and looseness material in itself, degradable substance can be selected to make, or even further, Made using the material for having facilitation after degraded to bone cell growth.
What is retrieved when the application submits heals applied to fracture anastomosis line closest to for documents, not retrieving Foldable structure composite biological film.Expand application field to be retrieved, CN201510716279.8 is due to proposing compound bio Film using when first pass through folding or convolution formed fibroin layer be internal layer, collagen layer is middle level, high polymer layer is outer layer Bridge grafting nerves support, belong to application field difference, but disclose more technical characteristic.But it does not still destroy the application Creativeness.It can be found from CN201510716279.8 accompanying drawing 3, the purpose for playing folding and convolution is by composite biological film Formed " concentric multi-layer cylinder structure ", change technical characteristic and the application be different, secondly its solve be " will fold or certificate Support after folding(Multi-layer cylinder structure composite biomembrane)Both ends and the nerve tract both ends blocked are sutured by surgical method " Its technical problem solved, the technique effect and the application of acquirement are entirely different, therefore do not destroy the creativeness of the application.
Brief description of the drawings
Fig. 1 is 4 in the present invention)When biology microstructure film be covered on model vertex, and wrap model vertex and Extend to the schematic diagram of model vertex both sides.
Fig. 2 is top view of the present invention.
Embodiment
With reference to figure 1, a kind of preparation method for the tip composite particles for improving union, comprise the following steps:
1)With fracture line is made after in vitro people's bone artificial fracture, it is cast in wax on fracture line, then waits wax to solidify later just Form U-typed model 1.Model 1 is taken off from fracture line.
2)Elastic layer, the medicine layer of moistening are made respectively, and the elastic layer is fine and close degradable or nondegradable life Thing film, medicine layer material be and the good degraded or non-degradable of human body bone bio-compatible, absorption do not absorb either or Porosity and looseness material, be also encapsulated with the medicine for having facilitation to sclerotin healing inside medicine layer.
3)The elastic layer of moistening is covered on the drift angle of model 1, the drift angle of model 1 is wrapped and extends to the drift angle of model 1 Both sides, then the medicine layer of moistening is covered on elastic layer, then the guide layer of moistening is covered on medicine layer;
4)Biological microstructure film is carried out to the detachment of width on demand;
5)After air-drying shape fixation Deng composite particles, the composite particles made are peeled off from model vertex.
Wax and elastic layer material are immiscible from each other, are easy to peel off from wax pattern after air-drying.

Claims (10)

1. a kind of preparation method for the tip composite particles for improving union, comprises the following steps:
1)It is " U " font and the model being coincide with fracture line section to make drift angle section in advance;
2)Elastic layer, the medicine layer of moistening are made respectively, the elastic layer is fine and close degradable or nondegradable biomembrane, Medicine layer material be and the good degraded or non-degradable of human body bone bio-compatible, absorb do not absorb either or it is porous Unconsolidated material, the medicine for having facilitation to sclerotin healing is also encapsulated with inside medicine layer;
3)The elastic layer of moistening is covered on model vertex, model vertex is wrapped and extends to model vertex both sides, then The medicine layer of moistening is covered on elastic layer, forms biological microstructure film;
4)Biological microstructure film is carried out to the detachment of width on demand;
5)After air-drying shape fixation Deng composite particles, the composite particles made are peeled off from model vertex.
2. a kind of preparation method of tip composite particles for improving union as claimed in claim 1, it is characterized in that:Fracture Line section after in vitro people's bone artificial fracture with being made.
3. a kind of preparation method of tip composite particles for improving union as claimed in claim 2, it is characterized in that:Drift angle Section is " U " font and the model identical with fracture line section is cast on fracture line with wax, then waits wax solidification later with regard to shape Into model, then model is taken off from fracture line.
4. a kind of preparation method of tip composite particles for improving union as claimed in claim 3, it is characterized in that:4) Before, biological microstructure film periphery is closed with that can not permeate the Medical Living Creature Gum of the stimulate neuronal growth factor and stem cell.
5. a kind of preparation method of tip composite particles for improving union as claimed in claim 4, it is characterized in that:It is described Elastic layer material is one or several kinds of mixing in PLA, collagen, fibrin, biogel, poly butyric ester Thing.
6. a kind of preparation method of tip composite particles for improving union as claimed in claim 5, it is characterized in that:It is described Elastic layer material is that can not permeate the Medical Living Creature Gum of the stimulate neuronal growth factor and stem cell.
7. a kind of preparation method of tip composite particles for improving union as claimed in claim 6, it is characterized in that:Medicine Rotating fields be and human body bone bio-compatible good fiber shape or areolation.
8. a kind of preparation method of tip composite particles for improving union as claimed in claim 7, it is characterized in that:Medicine The material of layer is using the material for having facilitation after degraded to bone cell growth.
9. a kind of preparation method of tip composite particles for improving union as claimed in claim 8, it is characterized in that:Medicine Layer material is azelon either cellulose or biogel or sterilization algal gel or antimicrobial activity charcoal.
10. a kind of preparation method of tip composite particles for improving union as claimed in claim 9, it is characterized in that:Medicine The combination of growth factor either stem cell or growth factor and stem cell is encapsulated with nitride layer.
CN201711021081.3A 2017-10-26 2017-10-26 A kind of preparation method for the tip composite particles for improving union Withdrawn CN107822744A (en)

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Application Number Priority Date Filing Date Title
CN201711021081.3A CN107822744A (en) 2017-10-26 2017-10-26 A kind of preparation method for the tip composite particles for improving union

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201711021081.3A CN107822744A (en) 2017-10-26 2017-10-26 A kind of preparation method for the tip composite particles for improving union

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CN107822744A true CN107822744A (en) 2018-03-23

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114425104A (en) * 2021-12-21 2022-05-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114425104A (en) * 2021-12-21 2022-05-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof
CN114425104B (en) * 2021-12-21 2023-03-03 中国人民解放军空军军医大学 Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof

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Application publication date: 20180323