CN108126241A - Tissue repair sticking patch, main body and preparation method - Google Patents
Tissue repair sticking patch, main body and preparation method Download PDFInfo
- Publication number
- CN108126241A CN108126241A CN201810170373.1A CN201810170373A CN108126241A CN 108126241 A CN108126241 A CN 108126241A CN 201810170373 A CN201810170373 A CN 201810170373A CN 108126241 A CN108126241 A CN 108126241A
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- China
- Prior art keywords
- tissue repair
- preparation
- small intestinal
- sticking patch
- intestinal submucosa
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- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 11
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
-
- 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
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Botany (AREA)
- General Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a kind of tissue repair sticking patch, main body and preparation method, wherein, the preparation method of tissue repair patch body, which is characterized in that include the following steps：Animal small intestinal submucosa is obtained, the animal small intestinal submucosa is carried out disinfection by the membranaceous or lamellar structure of animal small intestine, degreasing, take off cell, virus removal handles to obtain, using soda acid alternate treatment；The de- cell uses Solute mass percentage composition as 0.05 0.5% pancreas chymotrypsin solution；The small intestinal submucosa is obtained into main body through compound, compacting, superposition, dry, suture；By the main body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, the contact layer is animal small intestinal submucosa.Patch body prepared by the method for the present invention has the advantages of foreign body sensation is low, and mechanical property is good and prevents tissue adhesion.
Description
Technical field
The present invention relates to tissue repairing's technical fields, and in particular to a kind of tissue repair sticking patch, main body and preparation method.
Background technology
The present invention belongs to the relevant technologies related to the present invention for the description of background technology, be only used for explanation and just
In understanding present disclosure, should not be construed as applicant be specifically identified to or estimate applicant be considered the present invention be put forward for the first time
The prior art of the applying date of application.
Tissue injury or defect are clinically common illnesss, and wound, organ-tissue part lack as caused by operation in vivo
Damage, hernia, skin surface damage etc., seriously affects the quality of life of patient, is that must medically face and urgently to be resolved hurrily
Problem.
There are problems that immunogene and overtreating destroy material structure problem currently on the market for the sticking patch of tissue repair,
There is mechanical strength at a specified future date after existing non-crosslinked biomaterial implantation to decline, the palindromias such as hernia are caused when serious；And
Though the mechanics of biomaterials intensity after crosslinking is guaranteed but tissue is not easy to grow into and vascularization, and with micro- toxicity.In the presence of
Poor mechanical property, foreign body sensation generates by force and easily the shortcomings that tissue adhesion.
Invention content
The purpose of embodiments of the invention is to provide a kind of tissue repair sticking patch, main body and preparation method, the present invention is real
Applying the patch body of example offer has the advantages of foreign body sensation is low, and mechanical property is good and prevents tissue adhesion.
The purpose of the present invention is what is be achieved through the following technical solutions：
An embodiment of the present invention provides a kind of preparation methods of tissue repair patch body, include the following steps：
Obtain animal small intestinal submucosa, the animal small intestinal submucosa by animal small intestine membranaceous or lamellar structure
Carry out disinfection, degreasing, de- cell, virus removal handle to obtain, using soda acid alternate treatment；The de- cell uses Solute mass hundred
It is 0.05-0.5% pancreas chymotrypsin solution to divide content；
The small intestinal submucosa is obtained into main body through compound, compacting, superposition, dry, suture；
By the main body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, it is described
Contact layer is animal small intestinal submucosa.
Further, the suture uses nonabsorable suture；The suture is polyester and/or polypropylene material.
Further, the animal small intestinal submucosa includes the close to the first face of mucous layer and close to placenta percreta
Two faces, described is superposed to be overlapped facing towards overlying tissue to be repaired according to the second of animal small intestinal submucosa.
Further, the disinfection is at least one using following disinfection way：
The first solution of the membranaceous or lamellar structure of animal small intestine is impregnated into 5-90min, first solution is peroxide
The mass percentage of acetic acid is 0.01-1%, and the mass percentage of ethyl alcohol is the mixed aqueous solution of 1-10%；
By the membranaceous or lamellar structure of animal small intestine with molar concentration be 0.01-0.05M disodium ethylene diamine tetraacetate it is molten
Liquid impregnates 1-6h；
By the membranaceous or lamellar structure of animal small intestine with mass percentage be 0.01-1% sodium hydroxide solutions impregnate 2-
12h。
Further, the degreasing uses Solute mass fraction as 1%-5% alkaline solutions, and the solute is hydrogen-oxygen
Change at least one of sodium, sodium carbonate, sodium bicarbonate.
Further, the auxiliary that the degreasing passes through ultrasonication.
Further, the de- cell is at room temperature by the small intestinal submucosa in de- cell solution immersion treatment
0.5-4h terminates enzyme reaction using 1%-3% sodium hydroxides.
Further, the virus removal is that mass percentage is used to be mixed for 0.2%-2% Peracetic acid and ethyl alcohol
The mode that one or both of solution, sodium hydroxide solution that mass percentage is 1%-3% combine is respectively processed
1h-3h。
Further, dry select is lyophilized or is dried in vacuo.
Second aspect, the embodiment of the present invention provide a kind of tissue repair patch body, the tissue repair sticking patch
Main body is prepared by any of the above-described kind of preparation method.
The third aspect, an embodiment of the present invention provides a kind of preparation methods of tissue repair sticking patch, include the following steps：
By aforementioned body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, described connects
Contact layer is animal small intestinal submucosa.
Fourth aspect, an embodiment of the present invention provides a kind of tissue repair sticking patch, and the sticking patch is by above-mentioned preparation side
Method is prepared.
According to the above aspect of the present invention, the tissue repair of the present invention is at least had the following advantages that with sticking patch：
The degree for the treatment of control of immunogenicity, the alternate treatment being combined using soda acid, with reference to degreasing in the method for the present invention
De- cell processing, it is ensured that the immunogenicity of raw material reaches acceptable level, takes off cell using pancreas chymotrypsin, it is ensured that acellular
Residual does not destroy collagen structure simultaneously.
Sticking patch provided in an embodiment of the present invention is in contact using small intestinal submucosa with overlying tissue to be repaired, can not only be prevented
Adhesion is organized, and reduces the foreign body sensation of sticking patch；It is sutured using nonabsorable suture, improves the mechanical property of sticking patch.
Description of the drawings
It, below will be to attached drawing needed in embodiment description in order to illustrate more clearly of technical scheme of the present invention
It is briefly described：
Fig. 1 is the structure diagram of tissue repair sticking patch in the embodiment of the present invention；
Fig. 2 is that subcutaneous rat is implanted into design sketch of the sticking patch after 7 days in the embodiment of the present invention；
Fig. 3 is that subcutaneous rat is implanted into another design sketch of the sticking patch after 7 days in the embodiment of the present invention；
Fig. 4 is that subcutaneous rat is implanted into design sketch of the sticking patch after 6 months in the embodiment of the present invention；
Fig. 5 is that rat abdomen is implanted into the sticking patch design sketch of 3 months in the embodiment of the present invention；
Fig. 6 is that rat abdomen is implanted into repairing effect figure after sticking patch in the embodiment of the present invention；
Fig. 7 is that rat abdomen is implanted into another repairing effect figure after sticking patch in the embodiment of the present invention；
Fig. 8 is that rat abdomen is implanted into existing abiotic sticking patch design sketch after one month in the embodiment of the present invention.
Specific embodiment
The present invention is further discussed in detail with reference to the accompanying drawings and examples, it should be understood that attached drawing and implementation
Example is in order to which those skilled in the art are easier to understand technical scheme of the present invention, and cannot function as the limit of the scope of the present invention
It is fixed.
In following introductions, term " first ", " second " are only for descriptive purposes, and it is not intended that instruction or dark
Show relative importance.Following introductions provide multiple embodiments of the present invention, can replace or merge between different embodiments
Combination, therefore the present invention is it is also contemplated that include all possible combinations of recorded identical and/or different embodiment.Thus, such as
Fruit one embodiment includes feature A, B, C, another embodiment includes feature B, D, then the present invention also should be regarded as including containing
A, the embodiment of the every other possible combination of one or more of B, C, D, although the embodiment may be in the following contents
In have specific literature record.
Applicants have found that：In tissue repairing patch, the high molecular synthetic materials such as polypropylene, polyester are all thin because of it
The good adherency carrier of bacterium, bacterial adhesion thereon after can generate protect it from host immune defenses mechanism and antibiotic effect
Biofilm, so as to be able to locally survive and can cause the chronic infection of wound for a long time；And such material is implanted into abdominal cavity
It is interior, easily cause adhesion, foreign body sensation is extremely strong；Applicant further found that：Biological tissue's derived material is moved by the allosome or mammality of people
The membranaceous or lamellar structure of object handles the extracellular matrix with three dimensions frame structure formed through physics and chemistry and forms, tissue
Test is withstood in compatibility, stability, but clinical effectiveness is undesirable.The reason is that its drop of natural ingredient within the organization
Solution absorbs uncontrollable, so as to unstable mechanical property at a specified future date, easily cause recurrence, it is then desired to it is a kind of convenient for application completely newly
Tissue repairing patch meets the needs of clinical.
It is handled mostly using trypsase or without de- cell in same type of material processing at present.Immunogene problem and processing
There is mechanical strength at a specified future date after existing non-crosslinked biomaterial implantation and declines, when serious in excess destruction material structure problem
Lead to the palindromias such as hernia；And though mechanics of biomaterials intensity after crosslinking is guaranteed but tissue is not easy to grow into and blood vessel
Change, and with micro- toxicity.
An embodiment of the present invention provides a kind of preparation methods of tissue repair patch body, include the following steps：
Obtain animal small intestinal submucosa (SIS--small intestinal submucosa), the animal small intestine
Submucosa is carried out disinfection by the membranaceous or lamellar structure of animal small intestine, degreasing, take off cell, virus removal handles to obtain, using acid
Alkali alternate treatment；The de- cell uses Solute mass percentage composition as 0.05-0.5% pancreas chymotrypsin solution；
The small intestinal submucosa is obtained into main body through compound, compacting, superposition, dry, suture；
By the main body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, it is described
Contact layer is animal small intestinal submucosa.
An embodiment of the present invention provides a kind of preparation methods of tissue repair sticking patch, include the following steps：
Main body is prepared according to the method for above-described embodiment；
By the main body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, it is described
Contact layer is animal small intestinal submucosa.
The degree for the treatment of control of immunogenicity, the alternate treatment being combined using soda acid, with reference to degreasing in the method for the present invention
De- cell processing, it is ensured that the immunogenicity of raw material reaches acceptable level, takes off cell using pancreas chymotrypsin, it is ensured that acellular
Residual does not destroy collagen structure simultaneously.
Above scheme can achieve the object of the present invention, herein below on the basis of provide preferred embodiment.
The suture uses nonabsorable suture in some embodiments of the invention；The suture for polyester and/
Or polypropylene material.It will be clear that the suture using nonabsorable can greatly improve the mechanical property of sticking patch.
The animal small intestinal submucosa is included close to the first face of mucous layer and close to the second face of placenta percreta, at this
In some embodiments of invention, described is superposed to carry out facing towards overlying tissue to be repaired according to the second of animal small intestinal submucosa
Superposition.To note here is that：Small intestinal submucosa serosal surface side is rougher with respect to mucous membrane one side, and gap is larger between tissue,
It grows conducive to cell attachment.
In some embodiments of the invention, disinfection way is：The membranaceous or lamellar structure of animal small intestine is molten with first
Liquid impregnates 5-90min, and first solution is that the mass percentage of Peracetic acid is 0.01-1%, the quality hundred of ethyl alcohol
Divide the mixed aqueous solution that content is 1-10%；
In other embodiments of the present invention, disinfection way is：By the membranaceous or lamellar structure use mole of animal small intestine
The disodium ethylene diamine tetra-acetic acid solution of a concentration of 0.01-0.05M impregnates 1-6h；
In other embodiments of the present invention, disinfection way is：By the membranaceous or lamellar structure quality of animal small intestine
Percentage composition impregnates 2-12h for 0.01-1% sodium hydroxide solutions.
The degreasing uses Solute mass fraction as 1%-5% alkaline solutions in some embodiments of the invention, molten
Matter is at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, it will be clear that kind of the present invention to alkali solute
Class does not limit, as long as can meet the requirement of degreasing.
In some embodiments of the invention, by the auxiliary of ultrasonication, the auxiliary of ultrasonication can for the degreasing
To ensure abundant degreasing.
In some embodiments of the invention, the de- cell is at room temperature by the small intestinal submucosa de- thin
Cell lysis liquid immersion treatment 0.5-4h terminates enzyme reaction using 1%-3% sodium hydroxides.
In some embodiments of the invention, the virus removal is to use mass percentage as 0.2%-2% peroxides
The side that one or both of acetic acid and alcohol mixed solution, the sodium hydroxide solution that mass percentage is 1%-3% combine
Formula is respectively processed 1h-3h.
Freezing dry process takes -60-80 DEG C of quick-frozen modes in the present invention, and sample pre-freeze 1-6 hours is adjusted simultaneously
Vacuum condition, gradient frozen drying ensure that product surface is smooth uniform.
The present invention does not limit the specific steps of suture, it is preferred to use nonabsorable suture polyester, polypropylene, polytetrafluoro
The sutures such as ethylene stitch merga pass biogum and/or the compound small intestinal submucosa of physical compression mode is prepared.
In some embodiments of the invention, dry select is lyophilized or is dried in vacuo.
The method of the present invention effectively solves the problems, such as the immunogene for the treatment of process and excess processes problem, and upper big in application
The problem of big mechanical properties decrease at a specified future date for improving single creature sticking patch leads to recurrence, and product globality is good, without multiple
The Operation that conjunction process is brought, and it is obviously improved single high molecular material sticking patch or composite polymer material sticking patch and biological material
The foreign body sensation that material composite polymer material sticking patch is brought to patient reduces the risk that adhesion and infection occur.
Suture includes one or more sutures for having listed, based on polyester and/or polypropylene material, other nonabsorables seam
Suture supplemented by wire rod matter
Macromolecule cannot absorb sticking patch and be also easy to produce adhesion etc., the sticking patch combined with the biology prepared in operation with macromolecule
The difficulty made in performing the operation compared to reduction saves the time, and the mechanical property for enhancing sticking patch simultaneously, avoids crosslinked biological sticking patch group
Inducibility difference or uncrosslinked sticking patch are knitted quickly by the situation of tissue fluid enzymolysis failure.
De- cell takes off one or more of cell group using enzyme process including pancreas chymotrypsin, Dispase or hypertonic saline
Conjunction mode, and using Qula lead to one or both of SDS removal cell fragment.
An embodiment of the present invention provides a kind of tissue repair patch body, including：
Multilayer small intestinal submucosa material patch, after the small intestinal submucosa material patch is the processing of animal small intestine
Animal small intestinal submucosa material, small intestinal submucosa material patch described in multilayer, which is sewed and mend, to be fixed.
The patch of above method preparation is provided in some embodiments of the invention.
Fig. 1 is tissue repair patch structure schematic diagram of the present invention, as shown in Figure 1, one embodiment of the present of invention provides
A kind of tissue repair sticking patch, including：
Main body (1), including multilayer small intestinal submucosa material patch, the small intestinal submucosa material patch is small for animal
Intestinal tissue treated animal small intestinal submucosa, the small intestinal submucosa material patch described in multilayer, which is sewed and mend, to be fixed；
Contact layer (2), is bonded fixation with the main body (1), and the contact layer (2) with overlying tissue to be repaired for connecing
It touches.
Sticking patch provided in an embodiment of the present invention is in contact using small intestinal submucosa with overlying tissue to be repaired, can not only be prevented
Adhesion is organized, and reduces the foreign body sensation of sticking patch；It is sutured using nonabsorable suture, improves the mechanical property of sticking patch.
In some embodiments of the invention, small intestinal submucosa material patch can include multiple sticking patch monolithics, adjacent
The sticking patch monolithic between partly overlap fitting, the validity of sticking patch can be ensured by partly overlapping between multiple sticking patch monolithics；
To note here is that：The size that the present invention is overlapped between the quantity of sticking patch monolithic and sticking patch monolithic does not limit specifically
It is fixed, those skilled in the art can select according to demand appropriate sticking patch monolithic quantity (for example every layer include two, three, five
A sticking patch monolithic etc.), those skilled in the art can adjust overlapping area between sticking patch monolithic according to the specific requirements of reparation,
As long as it can guarantee the validity of sticking patch.
In some embodiments of the invention animal small intestine be sheet or membranaceous, sheet and it is membranaceous easily with it is to be repaired
The suture of tissue is also beneficial to the reparation of tissue；It will be clear that the present invention does not make to have to the concrete shape of small intestine
Body limits, as long as tissue repair can be completed.
The shape of tissue repair sticking patch is poroid, netted or taper in some embodiments of the invention, to be said here
Bright is：The present invention is not especially limited the concrete shape of sticking patch, in specific repair, according to the shape of overlying tissue to be repaired come
The shape of sticking patch is designed, patch shapes and the shape fixed position of overlying tissue to be repaired is realized, is conducive to the reparation of tissue.
In some embodiments of the invention, it sews and mend fixed using nonabsorable suture, nonabsorable suture (such as polyester
And/or polypropylene material) mechanical property of sticking patch can be greatly improved, it can effectively prevent repairing tissue due to mechanical property problem
Harmful effect caused by multiple.
The present invention is not especially limited the number of plies of main body (1) Small Intestine submucosa material patch, as long as can ensure
The repairing effect of sticking patch, in some embodiments of the invention, the number of plies are 2-16 layers, and those skilled in the art can root
According to needing that the suitable number of plies is selected to ensure repairing effect.
In some embodiments of the invention, the processing of small intestinal submucosa includes drying steps, for drying mode, sheet
Invention is not especially limited, and is preferably lyophilized or is dried in vacuo.
To note here is that：Animal small intestinal submucosa includes the close to the first face of mucous layer and close to placenta percreta
Two faces, in some embodiments of the invention, the first of animal small intestinal submucosa faces in the tissue repair sticking patch
To overlying tissue to be repaired, small intestinal submucosa serosal surface side is rougher with respect to mucous membrane one side, and gap is larger between tissue, is conducive to thin
Born of the same parents attach growth, and placenta percreta is superimposed with the alternate mode of mucous layer, while ensure that placenta percreta towards outside, is used according to product difference
Way can be divided into it is double-deck, four layers, six layers, eight layers, ten layers etc.；For the stacked system of small intestinal submucosa, the present invention does not limit
It is fixed, as long as can ensure the growth of cell in tissue repair.
The product is alternately to be superimposed sample surfaces multilayer through special die compression moulding processing, and stacked system is shown in figure
Show, be placed in the mold of special construction, combine the adjusting of freeze drier condition, product is pressed into what poroid, transverse and longitudinal was interlocked
Conical form, braid form that latticed, cluster integrates etc. meet the special shape of tissue repair requirement.
The small intestinal submucosa (SIS) of the present invention before treatment, can first carry out small intestine surface sterilizing with disinfecting,
Such as with one or more of alternately immersion treatments therein such as Peracetic acid, bromogeramine and/or alcohol.
In the disinfection of the present invention, degreasing, de- cell and virus removal processing procedure, it can also be suitably added phosphate, chlorination
The buffer solutions such as sodium, sodium bicarbonate adjust the solution system equilibrium in process.0.01-0.05mol/lPBS buffer solutions,
Control PH7.3-7.5.
Small intestinal submucosa is successively laid on special die, and controls plastic film mulch size, completes first layer first
Plastic film mulch needs to partly overlap in every layer, here to plastic film mulch direction every layer specific and sequence during plastic film mulch between adjacent two panels SIS
Do not make specific requirement, it should be noted that ensureing that the mechanical property in each direction is satisfied by requirement during plastic film mulch.
Some particular preferred embodiments of the present invention are given below：
Embodiment 1
A kind of preparation method of tissue repair patch body, includes the following steps：
Prepare sticking patch monolithic：Small intestinal submucosa material with random order is cleaned, is disinfected, ungrease treatment,
De- cell processing, virus removal, it is last freeze-dried or be dried in vacuo.
Wherein, it is described to disinfect thimerosal to be used to carry out immersion treatment, SIS to small intestinal submucosa at normal temperatures
Length and the volume ratio of thimerosal are 1：1cm/ml；
Specifically disinfection way is：With the Peracetic acid of Solute mass percentage composition 1% and the mixing water of 10% ethyl alcohol
Solution impregnates 45 minutes；
Thoroughly it is cleaned by ultrasonic with purified water after having disinfected, interchangeable purified water progress is repeatedly clear during cleaning as needed
It washes, it is general to clean 1-8 times；
Degreasing, the solvent are the solution of the mixing of sodium hydroxide and sodium bicarbonate that Solute mass percentage composition is 5%.
Renew fresh solution per secondary, to ensure abundant degreasing, processing procedure can pass through the aid in treatment of ultrasonication；With pure after having handled
Change 1-8 ultrasonic cleaning of water；
De- cell will take off cell solution at room temperature and be generally enzyme solutions, Solute mass percentage described in SIS and de- cell solution
Content is that the mixed solution in 0.5% pancreas chymotrypsin solution (pH7.0-8.0) and 3U/ml RNA enzyme solution carries out immersion treatment
0.5-4 hours.And Solute mass percentage composition is used to terminate enzyme reaction for 3% sodium hydroxide, the processing of above-mentioned de- cell can be with
Reach good treatment effect and ensure biocompatibility.It is 1 to handle volume ratio：20cm/ml (the bodies of SIS length and treatment fluid
Product ratio) it takes off and is alternately cleaned with purified water and PBS after cell has been handled, it can repeatedly replace purified water as needed and be cleaned, one
As be respectively washed 1-8 times；
Virus removal, uses the Solute mass percentage composition to be for 2% Peracetic acid alcohol mixture, Solute mass percentage composition
The mode that one or both of 3% sodium hydroxide combines is respectively processed 1.5h, then cleans 1-8 times, plays virus removal
Effect；
It is alternately to be superimposed sample surfaces multilayer through mold compression moulding processing, is placed in mold, combines freeze drier
Product is pressed into the conical form that cluster integrates by the adjusting of condition.
Embodiment 2
A kind of preparation method of tissue repair patch body, includes the following steps：
Prepare sticking patch monolithic：Small intestinal submucosa material with random order is cleaned, is disinfected, ungrease treatment,
De- cell processing, virus removal, it is last freeze-dried or be dried in vacuo.
Wherein, it is described to disinfect thimerosal to be used to carry out immersion treatment, SIS to small intestinal submucosa at normal temperatures
Length and the volume ratio of thimerosal are 1：18cm/ml.
Specifically disinfection way is：The disodium ethylene diamine tetra-acetic acid solution that molar concentration is 0.03M impregnates 5 hours；
Thoroughly it is cleaned by ultrasonic with purified water after having disinfected, interchangeable purified water progress is repeatedly clear during cleaning as needed
It washes, it is general to clean 1-8 times.
Degreasing, the solvent are the alkaline solution of sodium hydroxide that Solute mass percentage composition is 3%.Per it is secondary renew it is fresh molten
Liquid, to ensure abundant degreasing, processing procedure can pass through the aid in treatment of ultrasonication；With 1-8 ultrasound of purified water after having handled
Cleaning.
De- cell will take off cell solution at room temperature and be generally enzyme solutions, Solute mass percentage described in SIS and de- cell solution
Content carries out immersion treatment 3 hours for 0.5% pancreas chymotrypsin solution (pH7.0-8.0) and 50U/ml DNA enzymatics, mixed solution.
And Solute mass percentage composition is used to terminate enzyme reaction for 2% sodium hydroxide, the processing of above-mentioned de- cell can reach good
Treatment effect simultaneously ensures biocompatibility.It is 1 to handle volume ratio：10cm/ml (SIS length and the volume ratio for the treatment of fluid) takes off cell
It is alternately cleaned with purified water and PBS after having handled, can repeatedly replace purified water as needed and be cleaned, generally be respectively washed 1-
8 times.
Virus removal uses Solute mass percentage composition to carry out processing 3h for 3% sodium hydroxide, then cleans 1-8 times, rises
To the effect of virus removal.
It is alternately to be superimposed sample surfaces multilayer through mold compression moulding processing, is placed in the mold of special construction, combines
Product is pressed into braid form by the adjusting of freeze drier condition.
Embodiment 3
Prepare sticking patch monolithic：Small intestinal submucosa material with random order is cleaned, is disinfected, ungrease treatment,
De- cell processing, virus removal, it is last freeze-dried or be dried in vacuo.
Wherein, it is described to disinfect thimerosal to be used to carry out immersion treatment, SIS to small intestinal submucosa at normal temperatures
Length and the volume ratio of thimerosal are 1：15cm/ml.
Specifically disinfection way is：It is impregnated 8 hours for 1% sodium hydroxide solution with mass percentage.
Thoroughly it is cleaned by ultrasonic with purified water after having disinfected, interchangeable purified water progress is repeatedly clear during cleaning as needed
It washes, it is general to clean 1-8 times.
Degreasing, the solvent are that the alkaline solutions such as the sodium hydroxide that Solute mass percentage composition is 4% and sodium bicarbonate mix
The solution of conjunction.Renew fresh solution per secondary, to ensure abundant degreasing, processing procedure can pass through the aid in treatment of ultrasonication；Place
With 1-8 ultrasonic cleaning of purified water after having managed.
De- cell will take off cell solution at room temperature and be generally enzyme solutions, Solute mass percentage described in SIS and de- cell solution
Content carries out immersion treatment 3 hours for 0.3% pancreas chymotrypsin solution (pH7.0-8.0).And use Solute mass percentage composition
Enzyme reaction is terminated for 2% sodium hydroxide, the processing of above-mentioned de- cell can reach good treatment effect and ensure bio-compatible
Property.It is 1 to handle volume ratio：2cm/ml (SIS length and the volume ratio for the treatment of fluid) is taken off after cell has been handled with purified water and PBS
It alternately cleans, can repeatedly replace purified water as needed and be cleaned, is generally respectively washed 1-8 times.
Virus removal uses Solute mass percentage composition to handle 1h-3h, Ran Houqing for 0.2% Peracetic acid alcohol mixture
It washes 1-8 times, plays the role of virus removal.
It is alternately to be superimposed sample surfaces multilayer through mold compression moulding processing, is placed in the mold of special construction, combines
The adjusting of freeze drier condition, product is compressed into tablet form.
Embodiment 4
A kind of preparation method of tissue repair sticking patch, includes the following steps：
Main body and contact layer prepared by embodiment 1-3 any embodiments carry out it is compound, suppress, be dried to obtain the group
Reparation sticking patch is knitted, the contact layer is animal small intestinal submucosa.
Sticking patch application example prepared by the present invention and as follows with the comparison of existing sticking patch：
Using 3% yellow Jackets intraperitoneal injection of anesthesia rat (0.9ml/ is only), anesthesia lies on the back rat after weighing solid
It is scheduled on mold plank, specific operation method is as follows：First rat back villus is cleaned out, then is disappeared with Iodophor using shaver
Poison spreads the art towel that sterilized in operative site, is picked up back epidermis with tweezers, and back median incision is obtained using scalpel,
Along subcutaneously being detached to the sharp property in both sides, muscle layer is exposed, preprepared is passed through to the smooth implantation skin of sticking patch of physiological saline immersion
Under, left and right is each a piece of, and suture is fixed, rear to suture fascia and skin of back.Alcohol wipe sterilizes, then is wrapped up with gauze.
It avoids infecting caused by oral medicaments factor.It was put to death respectively at 7,30,60,90,180 days, observes sticking patch metamorphosis and surrounding
Tissue growth situation.
As a result it shows：Postoperative Growth in Rats situation is preferable, and pathological section is the results show that sticking patch has preferable bio-compatible
Property, while promote revascularization and normal surrounding tissue cell adherence, growth, increment.Show preferable repair efficiency.Such as
Shown in Fig. 2 and Fig. 3, subcutaneous rat is implanted into 7 days, has there is a large amount of fibroblast growths and angiogenesis；It is as shown in figure 4, subcutaneous
After implantation 6 months, a large amount of angiogenesis of patch faces.
Using 3% yellow Jackets intraperitoneal injection of anesthesia rat (0.9ml/ is only), anesthesia lies on the back rat after weighing solid
It is fixed, rat abdomen villus is cleaned out, with iodophor disinfection, spreads the art towel that sterilized, row abdomen median incision, along subcutaneously to both sides
The separation of sharp property, exposure muscle layer, using abdomen median line as symmetry axis by 1.5cm × 2cm sizes muscle together with peritonaeum en bloc resection, cruelly
Reveal abdominal cavity intestinal tube tissue, abdominal-wall defect experimental animal model is made.It is created ready through the notch that is more than that physiological saline impregnates
The smooth wound cut surface that is covered in of sticking patch for hindering face is fixed, then suture fascia and abdominal skin using continuous suture.Wine
Smart cleaning disinfection.It avoids infecting caused by oral medicaments factor.As shown in figure 5, three months sticking patch are merged with highly organized；Such as
Shown in Fig. 6, wound revision, tissue is grown into well, slightly sees sticking patch form；As shown in fig. 7, wound one month is as a result, without adhesion shape
Into.Fig. 8 is the result that abiotic sticking patch is used under the same terms：Abiotic sticking patch, adhesion are more serious.
This product is provided through China national Certification and Accreditation Administration qualification certification (measurement certification CMA), laboratory
Matter identification (2015002491K), China National Accreditation Service for Conformity Assessment accreditation (CNAS L3940), state food drug prison
Superintend and direct Qualification Approval (Shi Yaojian sections of medical instrument testing agency of management general bureau【2014】No. 51) medical instrument biomaterial examine
Assessing mechanism detects, and indices are qualified.
It, need to be into material according to Table A .1 and the Table A .1 (Continued) evaluation test content to be considered in GB/T16886.1-2011
Row cytotoxicity, pyrogen, intradermal reaction, sensitization, Acute systemic toxicity, Salmonella reversion test, TK gene mutation tests, chromosome aberration
The detections such as experiment, subchronic toxicity test, Implantation Test, haemolysis, it is as a result qualified.Meanwhile according to GB/T16886.17 (ISO
The requirement of standards such as 10993-17), we are also tested the biochemistry residue and physical property of hernia repairing sticking patch,
Ensure that it will not generate the biology harmfulness of related fields in Clinical practice, ensure the safety and effectiveness of product.
By the techniques such as de- cell, virus removal to inactivation of virus and remove (or reduction) animal derived material immunogenicity into
Row control ensures DNA residual controls in tolerance interval, acellular residual using special enzymatic treatment mode.In simultaneous selection
Food and medicine calibrating research institute of state is virus inactivated verification, and effect meets the requirements.
Selection is through China national Certification and Accreditation Administration qualification certification (measurement certification CMA), laboratory qualification
Assert (2015002491K), China National Accreditation Service for Conformity Assessment accreditation (CNAS L3940), state food drug surveilance
Manage Qualification Approval (Shi Yaojian sections of medical instrument testing agency of general bureau【2014】No. 51) medical instrument biomaterial inspection comment
Valency mechanism carries out the coherent detections such as this sticking patch specificity and nonspecific immune response, with similar product correlated performance comparing result
It is as follows：
Table 1
Table 2
Table 3
Table 1- tables 3 are product of the present invention and similar products at home and abroad physical property, and growth factor and endotoxin content compare
As a result, product of the present invention is all substantially better than similar products at home and abroad in all respects it can be seen from table 1- tables 3.
It is that technological means commonly used in the art can be used to realize, for example stitch for the part not limited in the present invention
How to be punched during conjunction, the density in pore size and hole, suture is using multiply suture or sub-thread suture etc., people in the art
Member can need to complete the reparation of tissue to select suitable conventional means according to specific, for various conventional means herein
It repeats no more.
It is described above to be merely a preferred embodiment of the present invention, it is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, that is made any repaiies
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (12)
1. a kind of preparation method of tissue repair patch body, which is characterized in that include the following steps：
Animal small intestinal submucosa is obtained, the animal small intestinal submucosa is carried out by the membranaceous or lamellar structure of animal small intestine
Disinfection, degreasing, de- cell, virus removal handle to obtain, using soda acid alternate treatment；The de- cell is contained using Solute mass percentage
It measures as 0.05-0.5% pancreas chymotrypsin solution；
The small intestinal submucosa is obtained into main body through compound, compacting, superposition, dry, suture；
By the main body and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch, the contact
Layer is animal small intestinal submucosa.
2. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the suture is adopted
With nonabsorable suture；The suture is polyester and/or polypropylene material.
3. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the animal is small
Intestinal mucosa lower floor is included close to the first face of mucous layer and close to the second face of placenta percreta, and described is superposed to according to animal small intestine
The second of submucosa is overlapped facing towards overlying tissue to be repaired.
4. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the disinfection is
Using at least one of following disinfection way：
The first solution of the membranaceous or lamellar structure of animal small intestine is impregnated into 5-90min, first solution is Peracetic acid
Mass percentage for 0.01-1%, the mass percentage of ethyl alcohol is the mixed aqueous solution of 1-10%；
The membranaceous or lamellar structure of animal small intestine is soaked with the disodium ethylene diamine tetra-acetic acid solution that molar concentration is 0.01-0.05M
Steep 1-6h；
By the membranaceous or lamellar structure of animal small intestine with mass percentage be 0.01-1% sodium hydroxide solutions impregnate 2-12h.
5. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the degreasing is adopted
Be 1%-5% alkaline solutions with Solute mass fraction, the solute is sodium hydroxide, in sodium carbonate, sodium bicarbonate at least
It is a kind of.
6. the preparation method of tissue repair patch body according to claim 5, which is characterized in that the degreasing is led to
Cross the auxiliary of ultrasonication.
7. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the de- cell
For at room temperature by the small intestinal submucosa in de- cell solution immersion treatment 0.5-4h, using 1%-3% sodium hydroxides end
Only enzyme reaction.
8. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the virus removal
To use the hydrogen that mass percentage is 1%-3% for 0.2%-2% Peracetic acid and alcohol mixed solution, mass percentage
The mode that one or both of sodium hydroxide solution combines is respectively processed 1h-3h.
9. the preparation method of tissue repair patch body according to claim 1, which is characterized in that the dry choosing
With freeze-drying or vacuum drying.
10. a kind of tissue repair patch body, which is characterized in that the tissue repair patch body is by claim 1-
Any one of 9 preparation method is prepared.
11. a kind of preparation method of tissue repair sticking patch, which is characterized in that include the following steps：
By main body according to any one of claims 10 and contact layer carry out it is compound, suppress, be dried to obtain the tissue repair sticking patch,
The contact layer is animal small intestinal submucosa.
12. a kind of tissue repair sticking patch, which is characterized in that the sticking patch is prepared as the preparation method described in claim 11
And it obtains.
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| CN112641999A (en) * | 2020-12-04 | 2021-04-13 | 陕西佰傲再生医学有限公司 | Film paving equipment and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0684844A1 (en) * | 1993-02-18 | 1995-12-06 | W.L. Gore & Associates, Inc. | A laminated patch tissue repair sheet material |
| CN102462561A (en) * | 2010-11-19 | 2012-05-23 | 北京迈迪顶峰医疗科技有限公司 | Small intestinal submucosa (SIS) soft tissue repair patch and preparation method thereof |
| CN106039404A (en) * | 2015-04-08 | 2016-10-26 | 上海宏创医疗科技有限公司 | Preparation method for extracellular matrix (ECM) composite biological patch |
| CN106267347A (en) * | 2016-08-16 | 2017-01-04 | 北京大清生物技术有限公司 | Biological sticking patch and preparation method thereof at the bottom of basin |
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2018
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0684844A1 (en) * | 1993-02-18 | 1995-12-06 | W.L. Gore & Associates, Inc. | A laminated patch tissue repair sheet material |
| CN102462561A (en) * | 2010-11-19 | 2012-05-23 | 北京迈迪顶峰医疗科技有限公司 | Small intestinal submucosa (SIS) soft tissue repair patch and preparation method thereof |
| CN106039404A (en) * | 2015-04-08 | 2016-10-26 | 上海宏创医疗科技有限公司 | Preparation method for extracellular matrix (ECM) composite biological patch |
| CN106267347A (en) * | 2016-08-16 | 2017-01-04 | 北京大清生物技术有限公司 | Biological sticking patch and preparation method thereof at the bottom of basin |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112641999A (en) * | 2020-12-04 | 2021-04-13 | 陕西佰傲再生医学有限公司 | Film paving equipment and application thereof |
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