CN107397980A - A kind of tissue repair film coating anti-blocking compositions and its application method - Google Patents
A kind of tissue repair film coating anti-blocking compositions and its application method Download PDFInfo
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- CN107397980A CN107397980A CN201710312690.8A CN201710312690A CN107397980A CN 107397980 A CN107397980 A CN 107397980A CN 201710312690 A CN201710312690 A CN 201710312690A CN 107397980 A CN107397980 A CN 107397980A
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- 239000000203 mixture Substances 0.000 title claims abstract description 37
- 230000017423 tissue regeneration Effects 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 15
- 239000007888 film coating Substances 0.000 title claims abstract description 9
- 238000009501 film coating Methods 0.000 title claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 63
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000000661 sodium alginate Substances 0.000 claims abstract description 27
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 27
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 27
- 239000012528 membrane Substances 0.000 claims abstract description 24
- 238000011049 filling Methods 0.000 claims abstract description 15
- 229920002521 macromolecule Polymers 0.000 claims abstract description 15
- 239000012530 fluid Substances 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- 239000000047 product Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000007654 immersion Methods 0.000 claims description 9
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 5
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 claims description 5
- 229920002581 Glucomannan Polymers 0.000 claims description 5
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- 229940046240 glucomannan Drugs 0.000 claims description 5
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- 229960003160 hyaluronic acid Drugs 0.000 claims description 5
- -1 hydroxypropyl Chemical group 0.000 claims description 5
- 239000002504 physiological saline solution Substances 0.000 claims description 5
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
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- 229920001503 Glucan Polymers 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
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- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
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- 230000008859 change Effects 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
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- 230000008439 repair process Effects 0.000 abstract description 7
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- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 6
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- 238000010146 3D printing Methods 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
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- 235000005291 Rumex acetosa Nutrition 0.000 description 1
- 240000007001 Rumex acetosella Species 0.000 description 1
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- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 238000005213 imbibition Methods 0.000 description 1
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- 210000003928 nasal cavity Anatomy 0.000 description 1
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- 235000016709 nutrition Nutrition 0.000 description 1
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of tissue repair film coating anti-blocking compositions and its application method, the anti-blocking compositions, its by following parts by weight of component component：30 ~ 60 parts of sodium alginate, 10 ~ 20 parts of macromolecule of filling, 10 ~ 40 parts of oligo-anion.Said composition can provide good anti-adhesive properties in the early stage, and after 12 weeks, gradually lose the function that prevents adhesion.Composition provided by the invention is when for some clinical operation materials, biological tissue's repair membrane can be made slowly to be merged with tissue, the interaction of repair membrane and tissue is buffered, reducing may trigger the antigen concentration of immune response to accumulate, and improve tolerance of the tissue to heterologous organisms material.The application of the present invention can reduce the difficulty of clinical operation, reduce second operation and follow-up nursing and treatment, meet the needs of to specific material properties.
Description
Technical field
The invention belongs to biomedical materials field, is specifically related to a kind of tissue repair film coating anti-blocking compositions
And its application method.
Background technology
Local organization because the effect of certain pathogenic factor damaged or death after, can be by the regeneration of neighbouring healthy cell
To repair, with recovery organization integrality.The speed of its process and whether complete influenced by factors, these factors are except being damaged
Organization type outside, also cause damage factor, nutrition, blood supply, infection, tissue defect how many etc..Living organism itself
Tissue repair generally comprises blood coagulation, inflammation and repairs the phase, and the wherein blood coagulation phase completes within several minutes, and inflammatory phase may continue 2-
7 days, reparation phase continued for several weeks was even more long, and under some serious conditions, complete tissue repair even can be more than more than 1 year, mistake
Long healing time can bring the pain of continuation to patient.With the progress of biomedical materials field, occur being used for pair
Injury tissue is covered and promoted the tissue repairing's film repaired.The main function of tissue repairing's film is exactly to being carried at injury tissue
For covering, it is isolated with the environment in the external world, reduces the breeding of pathogenic microorganisms, so as to reduce the inflammatory reaction of body, shortening is repaiied
The inflammatory phase acted on again, tissue is set to enter the reparation phase as early as possible.The application of this patching material not only improves the hand of tissue repair
Art mode, the extent of injury to human body is also reduced in big degree.Tissue repairing's film is varied, such as classical plastics, poly- ammonia
Ester, polyvinyl alcohol, rubber etc. synthesize macromolecule, after processing is film, can provide buffer action for tissue.Another material
For the macromolecule of biodegradable absorption, such as PLA, chitin, alginates, buffer action can not only be provided for wound, also
Sterilization, hemostasis and other effects can be played.As the new technologies such as the extraction of extracellular matrix, electrostatic spinning, 3D printing and method enter one
Step development, the function of tissue repairing's film of new generation are also divided into preventing tissue adhesion and promote two kinds of regeneration and restoration therewith.
Preventing tissue adhesion membrane is mainly used for isolating, and prevents affected part tissue and surrounding tissue adhesion after surgery.Clinically, outside
The patient of section's Post operation 90% may trigger adhesion and inflammation, especially in belly, angiocarpy, backbone, pelvic cavity etc., occur
Adhesion can cause serious complication, such as adhesive ileus, neurotrosis, blood vessel blockage compressing, infertility, often need
Second operation is wanted, great pain is brought to patient.Adherence preventing material can keep biologically inert in a long time, prevent
The tissue penetration and tactophily of its both sides, so as to play a part of preventing tissue and surrounding tissue adhesion after repairing.It is more at present
Kind being used for the material that prevents adhesion, all oneself has launch at home, is such as used for the polypropylene mesh of operation treating of hernia, due to it
Higher biologically inert, preferably support and buffer action can be played in vivo.Recently, absorbable material, as chitosan film,
Sodium alginate gel film etc., for preventing surgical wound surface adhesion that all there is good result, and meeting after long-time in vivo in vivo
It is degraded and absorbs, taken out without second operation, greatly reduces the pain of patient.
Promote the pathological regeneration reparation that regeneration and restoration film is mainly used for promoting affected part tissue.In conjunctiva repairing, consolidate
In some special type operations such as film repairing, nasal cavity, doctor can also use except the hemostasis of routine can be used to isolate dressing and promote tissue again
Raw repair membrane is merged as main or auxiliary material with accelerating regeneration.Such a operative site periphery is small and complicated, wound
Mouth narrow space, material needs to be modified to the shapes such as folding, nesting, therefore is unfavorable for multiple material and is used in conjunction with.Due to group
Knit intensive, material easily sticks together phenomenon with surrounding tissue, causes surgical field of view smudgy, it is postoperative can also influence to recover and after
Continuous treatment.But because operative site is small, regeneration is very fast, has been able to regeneration in short period inner tissue and form isolation
Film, and position function is crucial, it is not necessary to, be also not suitable for the material implantation therein that prevents adhesion, otherwise influenceing histoorgan just
Often work.In addition, during some biomaterial Clinical practices, it is too fast to trigger immune response with tissue bump contact.Therefore,
Demand to such material is to promote regeneration and restoration, while can possess 1-2 weeks short-term effect that prevents adhesion, subsequent material energy
Quickly with tissue fusion and being utilized.
Sodium alginate is can to provide one of material for the effect of preventing adhesion.ZL201380072748 discloses one kind by sea
The hydrogel thin film of the composition such as alginates and macromolecular hyaluronate, then it is used as the material to prevent adhesion for a long time by the use of this film
Material, and this film can be as the carrier of medicine, and in affected part, release medicine plays effect.But the material prepared by this patent
It is to be used to prevent adhesion for a long time, rather than was degraded quickly in a short time at 1-2 weeks.CN 201610798295 discloses one kind and prevented adhesion
Alginate dressing, CN 201480030318 discloses a kind of anti-adhesion gel using alginic acid as main component, be all by
It is used in long-term prevent adhesion.
But do not used pure sodium alginate as surgical operation implantation product typically.Its problem is that the method obtains
The characteristic of material be difficult to regulate and control.If it is desired to shorten its duration to prevent adhesion, it is considered that can be by reducing alginic acid
The concentration of sodium colloidal sol or the concentration of calcium ion and realize.But in material surface coating high concentration colloidal sol and sizing, due to first
Phase crosslinking points are more, and solution concentration is enough, and material surface energy forms close alginic acid Sodium/Calcium gel layer, but in gel layer still
May proceed to that ionomer reaction occurs, with the rising of the degree of cross linking, wherein retainable moisture is constantly extruded, final material table
Face forms one layer of fine and close hydrophobic membrane, and material is integrally changed into hydrophobic, has been unfavorable for creeping, regenerating for tissue completely.If with
Solvent and the setting agent processing of low concentration, due to strong non-directional between sodium alginate carboxyl anion and calcium cation be present
Property charge effect, with the progress of reaction, zwitterion in solution constantly even separates out to enrichment at initial stage crosslinking points, causes
Uniform gel can not be generated, what is ultimately resulted in is broken due to the active force of inside to dissipate for fragment, can not be attached to material,
Even can be too strong because of material water imbibition, sticked together on the contrary with wound.Therefore, it is difficult to by controlling colloidal sol and style keeping liquid dense
Degree, make material that there is the short-term effect that prevents adhesion.
To find out its cause, it is that the crosslinking of its ionic is too strong and uncontrollable.It is regular and intensive due to having on sodium alginate side chain
Carboxyl arrangement, cause its charge density very big, therefore relatively large with bivalent ions cross link force.It is ionic due to influenceing
The principal element of cross link force is exactly the density and molecular weight of ion, therefore, by the method for compounding, to pure sodium alginate colloidal sol
It is middle to add the material that structure is similar, material and molecular weight with relatively low ion concentration are low, it becomes possible to it is crosslinked to improve its
Performance, can finally be formed uniformly and have the film of some strength, make material that there are short-term anti-blocking properties.
The content of the invention
In order to solve the deficiency of existing biological adherence preventing material, it is an object of the invention to provide a kind of painting of tissue repair film
Cover and use anti-blocking compositions.
Another mesh of the present invention is to provide a kind of application method of tissue repair film coating anti-blocking compositions.
The another mesh of the present invention is the application for providing above-mentioned tissue repair film coating anti-blocking compositions.
The technical solution used in the present invention is：
A kind of tissue repair film coating anti-blocking compositions, its by following parts by weight of component component：Sodium alginate 30 ~ 60
Part, 10 ~ 20 parts of macromolecule of filling, 10 ~ 40 parts of oligo-anion；The sodium alginate, it glues under 1% aqueous solution state
Spend for 0.2 ~ 0.6 Pa s.
Preferably, the filling macromolecule gathers including HPMC, hyaluronic acid, konjaku glucomannan, Portugal
At least one of sugar.
Preferably, it is described to fill with high molecular weight average molecular weight more than 20000.
Preferably, the oligo-anion includes oligomeric sodium alginate, oligomeric oxycellulose, oligomeric gamma-polyglutamic acid
At least one of.
Preferably, the weight average molecular weight of the oligo-anion is 1000 ~ 8000.
The application method of above-mentioned anti-blocking compositions, comprises the following steps：
1）Raw material is fully swelled in water, physiological saline or physiological buffer, is prepared as the glue that concentration is 0.1 ~ 1.5% wt
Liquid；
2）The tissue repair film for needing to be coated fully is soaked in colloidal fluid；
3）The membrane material that immersion is completed is taken out, after blotting remained on surface liquid, spreads out and is immersed in 2 ~ 30min in crosslinked fluid；
4）After the completion of reaction, take out and clean, product is obtained after freeze-drying.
Preferably, step 3）Described crosslinked fluid is 0.5 ~ 2%wt calcium chloride water, the saturation calcium sulfate aqueous solution
At least one of supernatant.
Coating application in implantable biomedical devices of the above-mentioned anti-blocking compositions as tissue repair film.
Anti-blocking compositions described above as coating in implantable biomedical devices, especially in eye, nose, oral cavity group
Knit the application in reparation biomedical devices.
In embodiments of the present invention, it is after the anti-blocking compositions are formulated as solution, by it by coating, flowing
The mode such as prolong, infiltrate to be combined with biological tissue repair membrane, then being shaped in style keeping liquid, having biological tissue's repair membrane can be short
The coating of the effect that prevents adhesion of phase and play a role, rather than be individually individually used for this composition as forms such as film, gels
In preventing adhesion, the reason is that mechanical strength is poor after separately formed.
For the sodium alginate that the present invention uses under 1% aqueous solution state, viscosity is 0.2 ~ 0.6 Pa s, it is intended that this is viscous
Sodium alginate in the range of degree has suitable molecular weight, there is enough anion, can maintain the mechanical property of final product, institute
The crosslinking ability of offer can guarantee that composition after application, can play the effect of preventing adhesion.
The present invention is using the conduct of at least one of HPMC, hyaluronic acid, konjaku glucomannan, glucan
Filling macromolecule, it is all polysaccharide the purpose is to itself and sodium alginate, structure is similar, the relatively low material of ion concentration, can be in group
Play a part of scattered sodium alginate molecule in compound colloidal sol, by the physics effect of entwining etc., limit sodium alginate strand
Section moves freely, the anion disperseed in solution, mitigates accumulation effect during solion crosslinking, so that most
Whole material is more uniform.And by filling with high molecular weight average molecular weight be preferably more than 20000 in the present invention, be because this
Filling high polymer material more than molecular weight has more preferable viscosity and dispersiveness.
Present invention employs oligomeric sodium alginate, at least one of oligomeric oxycellulose, oligomeric gamma-polyglutamic acid are excellent
Choosing is used as oligo-anion component, and its reason is that such material has the anion of similar density with foregoing sodium alginate,
But there is relatively low molecular weight.This quasi-molecule equally can and calcium ion formed conjugate, this conjugate because molecular weight is low, and
The active force of cross-linking ion is weaker than foregoing macromolecular sodium alginate, and its cross-linking ion combined is easier to be lost in, in cross-linking ion
After number of dropouts reaches certain amount, such preferential depolymerization of oligomeric materials, material is integrally disintegrated and loses anti-blocking properties.The present invention
In, oligo-anion of the preferable weight-average molecular weight between 1000 ~ 8000, it is because the polymer molecular weight below 1000 is too low
Without crosslinking ability, and more than 8000 molecular weight crosslinking ability is too strong.The oligo-anion of the molecular weight ranges can pass through acid
The conventional methods such as degraded, oxidative degradation, control oxidation and UF membrane obtain.
In the present invention, described biological tissue's repair membrane, for the animal derived film with regeneration repair ability
It is referred to as, including but not limited to various tissue film's extracellular matrixs, collagem membrane, gelatin film, the support etc. for being loaded with growth factor, no
Including wanting the chitosan film of function, marine alga sorrel, PLA diaphragm, poly butyric diaphragm etc. based on preventing adhesion.The present invention
Only relate to this and be used as the composition and application method of coating material, and be not related to biological tissue's repair membrane in itself and its make
Preparation Method.
Compared with existing material, the beneficial effects of the invention are as follows：
The invention provides a kind of composition for possessing the short-term effect that prevents adhesion, said composition is coated on biological tissue's repair membrane
Afterwards, initial stage can provide good anti-adhesive properties, and after 1-2 weeks, the function that prevents adhesion gradually is lost, is then absorbed by organisms profit
With without cleaning treatment again.The application of the present invention can provide short-term preventing adhesiving effect for biological tissue repair film, drop
The difficulty of low clinical operation, second operation and follow-up nursing and treatment are reduced, meets the needs of to specific material properties.
Composition provided by the invention can make biological tissue's repair membrane slow with tissue when for some clinical operation materials
Slow fusion.Because animal derived biomaterial retains certain antigenicity toward contact, after the transfer such as with organizing directly big face
Product contact, may wherein antigenic substance concentration it is too high suddenly, trigger immune and inflammatory reaction and repel.Using this combination
After thing coating, equivalent to the interaction for having buffered repair membrane and tissue, the antigen concentration that may trigger immune response is reduced
Accumulation, improves tolerance of the tissue to heterologous organisms material.
Material therefor of the present invention is mainly the biological macromolecule such as polysaccharide, polyaminoacid, and without animal derived material, nothing is exempted from
Epidemic disease repels risk, the raw material that prevents adhesion preferably.
Calcium ion is rich in the material that the present invention uses, can be played a role in vivo in clotting mechanism so that material can have
There are certain haemostatic properties and promote to regenerate.
The present invention is applied to almost all creatures tissue repair film, by simple coating processes, can just cause biological group
Knitting repair membrane has the short-term effect that prevents adhesion, and technological process is short, and cost is low, is widely used, and has large-scale production meaning.
Embodiment
With reference to specific embodiment, the present invention is further illustrated, but is not limited thereto.
Part as described below is parts by weight, and unit is consistent.
Embodiment 1
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.2 ~ 0.3 Pa s for it）30 parts, filling macromolecule（Hydroxypropyl first
Base cellulose, weight average molecular weight >=20000）20 parts, oligo-anion（Weight average molecular weight is 1000 oligomeric sodium alginate）40
Part, it is well mixed, measures said composition 1.5g, be fully swelled in water, be prepared as the wt of concentration 1.5% colloidal fluid, by tissue
Repair membrane fully soaks in colloidal fluid, takes out the membrane material that immersion is completed, after blotting remained on surface liquid, spreads out and be immersed in
In 0.5%wt calcium chloride water after 2min, take out and clean, final products are obtained after freeze-drying.
Embodiment 2
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.3 ~ 0.4 Pa s for it）60 parts, filling macromolecule（Hyalomitome
Acid, weight average molecular weight >=20000）10 parts, oligo-anion（Weight average molecular weight is 8000 oligomeric gamma-polyglutamic acid）40 parts,
It is well mixed, said composition 0.1g is measured, is fully swelled in physiological saline, is prepared as the colloidal fluid that concentration is 0.1 wt%, will
Tissue repair film fully soaks in colloidal fluid, takes out the membrane material that immersion is completed, after blotting remained on surface liquid, spreads out and soak
Not in 2%wt calcium chloride water after 30min, take out and clean, final products are obtained after freeze-drying.
Embodiment 3
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.35 ~ 0.45 Pa s for it）40 parts, filling macromolecule（Konjaku
Glucomannan, weight average molecular weight >=20000）15 parts, oligo-anion（The oligomeric oxycellulose of weight average molecular weight 3000）10
Part, it is well mixed, measures said composition 0.5g and be fully swelled in physiological buffer, is prepared as the glue that concentration is 0.5% wt
Liquid, tissue repair film is fully soaked in colloidal fluid, take out the membrane material that immersion is completed, after blotting remained on surface liquid, stand
Open and be immersed in 1%wt calcium chloride water after 10min, take out and clean, final products are obtained after freeze-drying.
Embodiment 4
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.4 ~ 0.5 Pa s for it）50 parts, filling macromolecule（Gather Portugal
Sugar, weight average molecular weight >=20000）10 parts, oligo-anion（Weight average molecular weight be 3000 oligomeric sodium alginate, Weight-average molecular
Measure the oligomeric gamma-polyglutamic acid for 1500,1：1）20 parts, it is well mixed, measures said composition 1g, in physiological saline fully
Swelling, the colloidal fluid that concentration is 1% wt is prepared as, tissue repair film is fully soaked in colloidal fluid, take out what immersion was completed
Membrane material, after blotting remained on surface liquid, spread out and be immersed in saturation calcium sulfate aqueous solution supernatant after 15min, taking-up is washed
Only, final products are obtained after freeze-drying.
Embodiment 5
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.5 ~ 0.6 Pa s for it）40 parts, filling macromolecule（Gather Portugal
Sugar, HPMC, hyaluronic acid, 3:1:1, weight average molecular weight >=20000）10 parts, oligo-anion（Weight average molecular weight
In 2000 oligomeric oxycelluloses, weight average molecular weight in 4000 oligomeric gamma-polyglutamic acids 1:1）25 parts, it is well mixed, measures this
Composition 0.8g, is fully swelled in water, the colloidal fluid that concentration is 0.8% wt is prepared as, by tissue repair film in colloidal fluid
Fully immersion, the membrane material that immersion is completed is taken out, after blotting remained on surface liquid, spreads out and is immersed in 1.5%wt calcium chloride water
20min in solution, take out and clean, final products are obtained after freeze-drying.
Embodiment 6
Take sodium alginate（Under 1% aqueous solution state, viscosity is 0.45 ~ 0.55 Pa s for it）30 parts, filling macromolecule（Hydroxyl
Third methylcellulose, hyaluronic acid, konjaku glucomannan, glucan, 1:1:1:1, weight average molecular weight >=20000）It is 20 parts, oligomeric
Anion（The oligomeric sodium alginate of weight average molecular weight 8000, the oligomeric oxycellulose of weight average molecular weight 1000, weight average molecular weight
2000 oligomeric gamma-polyglutamic acid, 1:1:1）30 parts, it is well mixed, said composition 1.2g is measured, in water, physiological saline or life
Fully it is swelled in reason buffer solution, is prepared as the colloidal fluid that concentration is 1.2% wt, tissue repair film is fully soaked in colloidal fluid
Bubble, the membrane material that immersion is completed is taken out, after blotting remained on surface liquid, spreads out and is immersed in 1.8%wt calcium chloride waters
After 15min, take out and clean, final products are obtained after freeze-drying.
Experiment：
From long 2cm, money 1cm pig dermis extracellular matrix is as tissue repair film, to remove the pig dermis warp after fat
After 0.5%TritonX-100 aqueous solution oscillation cleanings 24h, rinsed, freezed with PBS, Co-60 sterilizing and be made, according to embodiment 1
Product is made in ~ 6 method.Comparative example 1,2 is the tissue repair film without processing.Comparative example 3 is commercially available Antiadhesive film (Johnson ＆ Johnson
INTERCEED), 4 be commercially available polylactic acid anti-adhesion film (trade name:It is strong general).
From rat as animal model, stomach wall is opened after anesthesia, above-mentioned material is sutured on its stomach wall, in postoperative
3d, 7d, 14d, 21d are put to death, and observe material and Abdominal adhesion situation, and observation result is as shown in table 1.
As seen from the results in Table 1, embodiment 1 ~ 6 can preferably prevent adhesion within 7 days；After 7 days, as composition is matched somebody with somebody
Than the difference of, concentration, embodiment 2,3 starts to degrade；After 14 days, each material all starts degraded to half adhesion state.It is and right
Material therefor is the rush regeneration and restoration material without anti-blocking properties in ratio 1,2, and it is just glued after performing the operation 3 days
Even, and with high adherence preventing material in comparative example 3,4, after its anti-blocking properties can remain to 21 days.
In summary, composition of the invention can make material have what is prevented adhesion in a short time after coated use
Ability, then, material can degrade and be absorbed and lose the actively effect of preventing adhesion.
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other any without departing from change, modification, replacement, combination, the simplification made under essence and principle of the invention, be
Equivalent replacement mode, is included within protection scope of the present invention.
Claims (8)
1. a kind of tissue repair film coating anti-blocking compositions, its by following parts by weight of component component：Sodium alginate 30 ~
60 parts, filling with 10 ~ 20 parts of macromolecule, 10 ~ 40 parts of oligo-anion；The sodium alginate, its under 1% aqueous solution state,
Viscosity is 0.2 ~ 0.6 Pa s.
2. anti-blocking compositions according to claim 1, it is characterised in that：The filling includes hydroxypropyl with macromolecule
At least one of cellulose, hyaluronic acid, konjaku glucomannan, glucan.
3. anti-blocking compositions according to claim 2, it is characterised in that：The high molecular weight average molecular weight of the filling
More than 20000.
4. anti-blocking compositions according to claim 1, it is characterised in that：The oligo-anion includes oligomeric alginic acid
At least one of sodium, oligomeric oxycellulose, oligomeric gamma-polyglutamic acid.
5. anti-blocking compositions according to claim 4, it is characterised in that：The weight average molecular weight of the oligo-anion is
1000~8000。
6. the application method of the anti-blocking compositions described in any one of Claims 1 to 5, comprises the following steps：
1）Raw material is fully swelled in water, physiological saline or physiological buffer, is prepared as the glue that concentration is 0.1 ~ 1.5% wt
Liquid；
2）The tissue repair film for needing to be coated fully is soaked in colloidal fluid；
3）The membrane material that immersion is completed is taken out, after blotting remained on surface liquid, spreads out and is immersed in 2 ~ 30min in crosslinked fluid；
4）After the completion of reaction, take out and clean, product is obtained after freeze-drying.
7. application method according to claim 6, it is characterised in that：Step 3）Described crosslinked fluid is 0.5 ~ 2%wt chlorine
Change at least one of supernatant of the calcium aqueous solution, the saturation calcium sulfate aqueous solution.
8. anti-blocking compositions described in claim 1 ~ 7 as tissue repair film coating in implantable biomedical devices
Application.
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| CN109045355A (en) * | 2018-07-18 | 2018-12-21 | 昆明理工大学 | A kind of compound porous bone renovating material and preparation method thereof |
| CN109498847A (en) * | 2018-10-29 | 2019-03-22 | 赵顺全 | A kind of preparation method of degradable hemostatic bacteriostatic biological medicinal membrane |
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