CN2917585Y - Biotype artificial cornea - Google Patents

Abstract

The utility model discloses a bionic and artificial cornea, which is structured by base material (1) made by animal cornea which is fixed by non-aldehyde fixer and carried out antigenic treatment. The utility model has advantages of that the formation and three-dimensional structure are both similar to cornea of human, which is free from immunogenicity to induct and promote regeneration of the cornea. The utility model can be degraded matching the regeneration of cornea, and speed of the degradation and regeneration of the cornea can be synchronous by adjusting fixing condition of cross connection. Physical and mechanical performances are close to human cornea. The utility model is an ideal carrier or frame for rebuilding of cornea due to stable conformation and good flexibility, which can be processed to various curvatures and will not swell in water.

Description

Artificial biological cornea

Technical field

This utility model relates to a kind of device that is used for the damaged reconstruction of cornea, belongs to the embedded type medical apparatus and instruments.

Background technology

It is blind that corneal injury or pathological changes cause, is one of ophthalmology common disease, treats by the corneal transplantation of remains donations at present.The difficulty but corneal transplantation is originated on the one hand, immune on the other hand rejection problem also often makes graft failure.Transplant the needs that can not satisfy treatment far away by human cornea.Therefore, the scholar attempts exploitation and treats the damaged disease of human corneal with animal corneal, there is research directly to carry out corneal transplantation with animal corneal, because of rejecting to fail to overcome, immunity fails, also there is research to reach simply to disinfect through freezing and makes the artificial cornea's with animal corneal, because of going antigen not thorough, histocompatibility is not good enough and fail to be accepted by human body, obtains effectively breakthrough so far with animal corneal system artificial cornea's research.

Summary of the invention

The purpose of this utility model provides a kind of good biocompatibility, can be degraded and absorbed, can induce the regenerated artificial biological cornea of cornea.

Technical solution of the present utility model is: it is by being that base material constitutes through the crosslinked animal corneal fixing and that go antigen to handle of no-aldehyde fixative.

Animal corneal easily is degraded by microorganisms or decomposes, need to make it crosslinked fixing with fixative, use the glutaraldehyde agent that fixes traditionally, residual toxicity is arranged, we select the no-aldehyde fixative for use, as epoxide, two acid diamides, vulcabond, Polyethylene Glycol or carbodiimides, just there is not this shortcoming, with the epoxide is example, when the application epoxide replaces aldehydes to fix reagent, because epoxide is very unstable, the open loop cross-linking reaction takes place easily, the control reaction condition can accomplish to make its cross-linking products very stable, degraded is not easily only grown at regenerating tissues, when propagation needs its silkworm erosion, secrete kallikrein, fibrinolysin, under the collaborative collagenase effect of glucocorticoid, it slowly could be decomposed into polypeptide and aminoacid, and absorb.A kind of like this passive type degraded is synchronous with the regeneration of tissue, is that the reproducibility that helps organizing is most repaired, and does not have the residual toxicity of aldehydes; According to modern immunology theory, the antigenicity of animal tissue mainly is to cause that by the active group of some specific position in the protein and special conformation these active groups mainly are-OH-NH₂-SH etc., special conformation then mainly is because some special hydrogen bond of protein molecule coiled strand causes, when handling animal corneal, easily combine with these groups with one or more with the active reagent (as anhydride, acyl chlorides, amide, epoxide etc.) that these groups react, it is closed, thereby effectively removes its antigen, simultaneously, also use strong hydrogen bonding reagent (as guanidine compound), displacement causes the hydrogen bond of special conformation, changes its conformation, just can effectively eliminate its antigenicity.

As a kind of prioritization scheme, coupling has and contains the polypeptide or the glycosaminoglycan active component that can adhere to somatomedin on substrate surface, forms the active surface layer.One of described polypeptide is formed by 16 lysines (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P) and cysteine (C) polycondensation, and described glycosaminoglycans is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, Heparan sulfate or keratan sulfate.These polypeptide or glycosaminoglycans have wide spectrum to adhere to and enrichment to somatomedin, maybe can excite the undifferentiated cell directed differentiation, thereby have the function of the reproducibility reparation of inducing body tissue.

Described no-aldehyde fixative is to be easy to protein molecule crosslinked reagent such as in epoxide, two acid diamides, vulcabond, Polyethylene Glycol or the carbodiimides reagent one or both take place, and the epoxide here can be a monoepoxide

It also can be di-epoxide

Here R=H, C_nH_2n+1-, n=0-10; Can also be low polyepoxide such as poly(propylene oxide).

Described active reagent can be small molecular organic acid acid anhydride, acyl chlorides, amide or epoxide; Strong hydrogen bonding reagent is guanidine compound.

Described coupling agent be two acid diamides, dicarboxylic anhydride, di-epoxide or other can with-NH₂,-OH ,-COOH play the bifunctional reagent of condensation reaction.

The utility model has the advantages that: its composition and three dimensional structure and people's cornea is quite similar, non-immunogenicity, can induce and promote cornea regeneration, can do the compliance degraded, regulate and control crosslinked rigid condition and can control its degradation speed and cornea regeneration speed basic synchronization with the regeneration of cornea.Physical and mechanical property is close with people's cornea, form stable, and pliability is good, can be processed into different curvature, and not swelling in water is ideal carrier or the support that carries out cornea reconstruction.

Description of drawings

Accompanyingdrawing 1 is the structural representation of this utility model embodiment;

Accompanyingdrawing 2 is the vertical sectional view of this utility model embodiment;

1, base material, 2, the active surface layer.

The specific embodiment

Embodiment:

As illustrated in fig. 1 and 2, artificial biological cornea, by being thatbase material 1 constitutes through the crosslinked animal corneal fixing and that go antigen to handle of no-aldehyde fixative, coupling has and contains the polypeptide or the glycosaminoglycan active component that can adhere to somatomedin, formationactive surface layer 2 onbase material 1 surface.One of described polypeptide is formed by 16 lysines (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P) and cysteine (C) polycondensation, and described glycosaminoglycans is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, Heparan sulfate or keratan sulfate.

The preparation method of artificial biological cornea of the present utility model may further comprise the steps:

(1), selects materials: collect the fresh healthy swine eyeball, put into special-purpose freezing the transporting back of bottle of preserving;

(2), pretreatment: win animal corneal, and prune smooth; Inserting artificial tears or glycerol preserves in the liquid, under-18 ℃ of low temperature freezing 24 hours, take out, after thawing, with TritonX (Triton X-100), cholic acid receive, hydroxymethyl aminomethane (Tris), dodecyl semi-annular jade pendant acid sodium (SDS) or CHAPS surfactant solution soaked 16～20 hours, perhaps use pepsin, trypsin or the mixed enzyme solution soaking of the two 2～4 hours, clean ultrasonic cleaning in case of necessity 10～20 minutes;

(3), crosslinked fixing: as to place the epoxide fixative, the collagen molecules under the room temperature in thecrosslinked fixing substrate 1 8～48 hours;

(4), remove antigen: use in active reagent anhydride or methylating reagent or epoxidesealing base material 1 protein specific activity group-OH or-NH₂Or-SH, and, change special conformation with the special hydrogen bond in the strong hydrogen bonding reagent hydrochloric acid guanidine solution displacement base material protein molecule coiled strand;

(5), surface activity is modified: the polypeptide and the glycosaminoglycans active component that form by 16 lysines of coupling agent coupling (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P) and cysteine (C) polycondensation on the surface ofbase material 1 formactive surface layer 2.

(6), packing: after the biocide sterilization, under aseptic technique, be encapsulated in the bottle that fills preservation liquid.

Claims (1)

1, a kind of artificial biological cornea is characterized in that: it is by the formed base material of animal corneal (1), and coupling is formed at the lip-deep active surface layer (2) that contains polypeptide or glycosaminoglycan active component of base material (1).

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