CN105833344B - A kind of injection aquagel is preparing the application in Ocular tamponades - Google Patents
A kind of injection aquagel is preparing the application in Ocular tamponades Download PDFInfo
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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Abstract
The invention discloses the applications in a kind of injection aquagel within the eye filler, it is characterized in that being used as Ocular tamponades application in vitrectomy, and as intraocularly with drug carrier application；The injection aquagel is formed by two doses, first dose is the glue containing oxidation of polysaccharides, second dose is the glue containing chitin derivativ and/or collagen, two doses are respectively charged into two injection-tubes of Double-body syringe, two doses of glues are injected simultaneously through Double-body syringe, it is mixed, is crosslinked in bolus infusion processes, is i.e. the dialdehyde base of oxidation of polysaccharides is crosslinked with the amino of chitin derivativ and/or collagen to react, and being formed has viscoelastic hydrogel.The constituent of hydrogel of the invention is large biological molecule, is different from chemical macromolecule, and also without introducing small molecule crosslinking agent, good biocompatibility, degradable absorption has no toxic side effect, and safety is good.
Description
Technical field
The present invention relates to a kind of ophthalmic medical articles, are preparing Ocular tamponades more particularly to a kind of injection aquagel
In application.
Background technique
Vitreum is a kind of colorless and transparent colloid in eyeball rear cavity, is filled between crystalline lens and retina,
Occupy be more than 2/3 eyeball volume, main component includes water, collagen, hyaluronic acid, proteoglycan etc..Vitreum is
Retina provides support appropriate, protects the ocular tissue of surrounding, and light is enable to reach the receptor at eyeball rear, adjusts intraocular
Oxygen content and eyeball shape, while allowing the diffusive transport of metabolin He other solutes.Vitrectomy is important eye
Section's operation, for treating ophthalmology disease, such as retinopathy, detached retina.With the development of operation on vitreous technology,
Indication range constantly expands.Vitreous excision needs to carry out vitreous chamber filling, and filler is filled in vitreous chamber, press
Retina keeps it in correct position and keeps eyeball shape, thus vitreum filler become influence surgical effect it is important because
Element.
The vitreum filler clinically used at present mainly has gas, silicone oil, perfluorocarbon liquids etc., these fillers
Suitable for the vitreum filling under different surgery situations, but there are still many complication.As the gas filling time is short and may draw
Lenticular opacities etc., perfluorocarbon liquids toxicity with higher are played, common silicone oil filling easily occurs emulsification and to ocular tissue
There are certain toxicity, the complication such as Chang Yinqi glaucoma, cataract.Especially intraocular pressure is increased clinical very normal after vitreum filling
See, serious intraocular hypertension can cause ischemic and lead to visual loss, and long-term chronic durative intraocular hypertension may also damage view mind
Through.
Researcher is attempted in terms of artificial vitreous's filler, such as contains polyethylene glycol, polyvinyl alcohol or vinyl
The artificial synthetic hydrophilic polymer hydrogel such as pyrrolidones is as vitreous substitute.But have been reported that display (Wang Xianglin, Zhang Shun
It is clear, Quan Yuanlu, You Shiping.Polyvinyl alcohol hydrogel vitreous replacement animal experimental observation.Chongqing Medical institute journal, 1984
1 phase, 8-10 pages), polyvinyl alcohol hydrogel incidence of cataract in the zoopery of vitreous replacement is up to 73%, secondary
Glaucoma incidence is 38%, and it is unsatisfactory that display synthesizes the biocompatibility shown when chemical macromolecule absorbs within the eye.Cause
This, is using natural large biological molecule, rather than chemical synthesis macromolecular, it is the important trend that research prepares vitreum filler.
The Chinese invention patent of 102762647 A of Publication No. CN discloses a kind of hydrogel of two hydrazides crosslinking-oxidization hyaluronic acids
Polymer, substitute of the hydrogel as vitreous body of eye.Although hyaluronic acid have preferable biocompatibility, small point
The introducing of sub- crosslinking agent can not remove within the eye, and to ocular tissue's cell, there are certain side effects after being absorbed by ocular tissue.Therefore,
Clinically lack ideal vitreum filler at present.
Summary of the invention
The object of the present invention is to provide a kind of good biocompatibility, it is degradable absorb, have no toxic side effect, safety is good can
Injection hydrogel is preparing the application in Ocular tamponades, to make up the above-mentioned deficiency of the prior art.
A kind of injection aquagel of the invention application in filler within the eye, it is characterized in that the injection aquagel
It is used as Ocular tamponades application in ophthalmologic operation, Ocular tamponades application is used as especially in vitrectomy, with
And as intraocularly with drug carrier application；The injection aquagel is formed by two doses, and first dose is the glue containing oxidation of polysaccharides,
Second dose is the glue containing chitin derivativ and/or collagen, two doses of two injection-tubes for being respectively charged into Double-body syringe
In, two doses of glues are injected simultaneously through Double-body syringe, are mixed, are crosslinked in bolus infusion processes, is i.e. the dialdehyde base of oxidation of polysaccharides
It crosslinks and reacts with the amino of chitin derivativ and/or collagen, being formed has viscoelastic hydrogel.
Drug can also be contained in described second dose, the injection aquagel formed is as intraocularly answering with drug carrier
With.
The oxidation of polysaccharides is the oxidation of polysaccharides of the base containing dialdehyde, is further the heparin of the base containing dialdehyde, containing dialdehyde
The oxidized chondroitin sulphate of base, the oxidized sodium alginate of the base containing dialdehyde, the base containing dialdehyde oxidation fucoidin, the base containing dialdehyde oxygen
Change starch, the acetate starch of the base containing dialdehyde and other starch derivatives, the oxidated carboxymethyl cellulose of the base containing dialdehyde, containing dialdehyde
The oxidation hydroxyethyl cellulose of base, the oxidation hydroxypropyl cellulose of the base containing dialdehyde and other cellulose derivatives, the base containing dialdehyde
Aoxidize the oxygen of chitosan, the oxidation hydroxyethyl chitosan of the base containing dialdehyde, the oxidation hydroxypropyl chitosan of the base containing dialdehyde, the base containing dialdehyde
Change the oxidated carboxymethyl chitosan and other shells of hydroxyl butyl chitosan, the oxidation succinyl-chitosan of the base containing dialdehyde, the base containing dialdehyde
The oxygen for aoxidizing ethoxyl chitin, the oxidation Hydroxypropyl chitosan of the base containing dialdehyde, the base containing dialdehyde of polysaccharid derivative, the base containing dialdehyde
Change hydroxyl butyl chitin, the base containing dialdehyde oxidated carboxymethyl chitin and other bases containing dialdehyde oxidated chitin derivative, contain
The oxidized hyaluronic acid of dialdehyde base, the oxidized guar of the base containing dialdehyde, the base containing dialdehyde oxidation hydroxypropyl guar gum and other contain
One of the oxidized guar derivative of dialdehyde base, the oxidized dextran of the base containing dialdehyde, oxidized dextran of the base containing dialdehyde
Or the oxidation of polysaccharides of other bases containing dialdehyde that several or those skilled in the art can prepare.In the oxidation of polysaccharides of the base containing dialdehyde
The percentage that the sugar unit of the base containing dialdehyde accounts for the total sugar unit of polysaccharide molecule is 1%~70%；The oxidation of polysaccharides of the base containing dialdehyde is in glue
In concentration expressed in percentage by weight be 1%~25%, the solvent in glue is sterile water, physiological saline, physiological balance liquid or this field skill
Other aqueous medical use liquids that art personnel know, such as Glucose Liquid.
Chitin derivativ in described second dose is ethoxyl chitin, Hydroxypropyl chitosan, hydroxyl butyl chitin, carboxylic
Methyl chitin, hydroxyethyl chitosan, hydroxypropyl chitosan, hydroxyl butyl chitosan, carboxymethyl chitosan, in succinyl-chitosan
One or more；The concentration expressed in percentage by weight of the chitin derivativ and/or collagen in glue is 1%~20%, glue
Solvent in liquid is sterile water, physiological saline, physiological balance liquid, or those skilled in the art will know that other aqueous Medical liquids
Body, such as Glucose Liquid.
The glue of the oxidation of polysaccharides is also possible to oxidation of polysaccharides pulvis and solvent individualism, prepared before use；Institute
The glue of the chitin derivativ and/or collagen stated, be also possible to chitin derivativ and/or collagen protein powder with it is molten
Agent individualism, prepared before use.Pulvis is easier to save.
Injection aquagel of the present invention is preparing the application in Ocular tamponades, in experimental rabbit vitreous excision hand
In art as Ocular tamponades application the experimental results showed that, injection aquagel of the present invention is filled out as Ocular tamponades
It is charged in vitreous chamber, there is good filling effect, retina can be pressed and be maintained at correct position and keep eyeball shape,
Good in optical property, does not influence intraocular pressure, does not influence corneal endothelium quantity and aqueous humor circulation system, intraocular good biocompatibility, can be
Intraocular degradation absorbs, and does not need second operation taking-up, is a kind of ideal intraocular vitreum filler, tool without toxic side effect
There is vast market prospect.
Injection aquagel of the present invention is applied in preparing Ocular tamponades, and the injection aquagel can be with
As the carrier of intraocular medication, when hydrogel injection fillers of the invention to it is intraocular when, drug also with injection fillers to intraocular,
With the degradation of hydrogel, drug gradually discharges, and plays therapeutic effect, while reducing times for spraying, while having well
Intraocular biocompatibility and biological safety, equally have a vast market foreground.
Injection aquagel of the present invention is applied in preparing Ocular tamponades, and the constituent of hydrogel is biology
Macromolecular is different from chemical macromolecule, also without introducing small molecule crosslinking agent, good biocompatibility, degradable absorption, nontoxic pair
Effect, safety are good.
Detailed description of the invention
Fig. 1 is the postoperative 2w(1 of new zealand rabbit), 8w(2), 12w(3) and slit lamp observation figure.
Fig. 2 is the postoperative varieties of intraocular pressure figure of new zealand rabbit.
Fig. 3 is the postoperative 2w(A of new zealand rabbit), 8w(B), 12w(C) and eye ultrasound diagnosis figure.
Fig. 4 new zealand rabbit corneal endothelial cells quantity variation diagram.
Specific embodiment
With reference to the accompanying drawing and by specific embodiment come present invention be described in more detail.
One, the preparation of oxidation of polysaccharides
Embodiment 1: the preparation of oxidized chondroitin sulphate
Chondroitin sulfate 12.0g is weighed, is added in 500ml Erlenmeyer flask, adds water 200ml, stirring and dissolving uses 1mol/L
Aqueous hydrochloric acid solution tune pH value to pH5.0, oxidant NaIO is added41g, sealing are protected from light stirring oxidation reaction 18h at 4 DEG C.
Reaction finish, by reaction solution is fitted into molecular cut off be 3000 dalton bag filter in, be protected from light, at 4 DEG C distilled water dialyse for 24 hours,
Wherein every 6h replacement distilled water is primary.After dialysis, the liquid in bag filter is freeze-dried 48h, system in freeze drier
The oxidized chondroitin sulphate 11.3g of dialdehyde base must be contained, double percent aldehydes are that the bis- percent aldehydes of 2.5%(refer to polysaccharide
The sugar unit of the base containing dialdehyde accounts for the percentage of the total sugar unit of polysaccharide molecule in molecule, similarly hereinafter).
Embodiment 2: the preparation of oxidized starch
Starch 15g is weighed, is added in 500ml Erlenmeyer flask, water 200ml, heating stirring dissolution, with 5%(weight hundred are added
Oxidant NaIO is added to pH5.5 in aqueous acetic acid tune pH value point ratio, similarly hereinafter)43.5g, sealing, is protected from light stirs at room temperature
Mix oxidation reaction for 24 hours.Reaction is finished, and reaction solution is fitted into the bag filter that molecular cut off is 3000 dalton, is protected from light, at 4 DEG C
Distilled water is dialysed for 24 hours, wherein every 6h replacement distilled water is primary.After dialysis, by the liquid in bag filter in freeze drier
It is freeze-dried 48h, the oxidized starch 13.5g of the base containing dialdehyde is made, double percent aldehydes are 12.5%.
Embodiment 3: the preparation of oxidized hyaluronic acid
Hyaluronic acid 5g is weighed, is added in 1000ml Erlenmeyer flask, adds water 500ml, stirring and dissolving, with 5%(weight hundred
Oxidant NaIO is added to pH5.5 in aqueous acetic acid tune pH value point ratio, similarly hereinafter)42.5g, sealing, is protected from light stirs at room temperature
Mix oxidation reaction for 24 hours.Reaction is finished, and reaction solution is fitted into the bag filter that molecular cut off is 3000 dalton, is protected from light, at 4 DEG C
Distilled water is dialysed for 24 hours, wherein every 6h replacement distilled water is primary.After dialysis, by the liquid in bag filter in freeze drier
It is freeze-dried 48h, the oxidized hyaluronic acid 3.9g of the base containing dialdehyde is made, double percent aldehydes are 30.8%.
Embodiment 4: the preparation of oxidized sodium alginate
Sodium alginate 15g is weighed, is added in 1000ml Erlenmeyer flask, adds water 800ml, stirring and dissolving, with 1mol/L's
Oxidant KIO is added to pH5.0 in aqueous hydrochloric acid solution tune pH value49g, sealing are protected from light stirring oxidation reaction 36h at 4 DEG C.Instead
Should finish, by reaction solution be fitted into molecular cut off be 3000 dalton bag filter in, be protected from light, at 4 DEG C distilled water dialysis for 24 hours,
In every 6h replacement distilled water it is primary.After dialysis, the liquid in bag filter is freeze-dried 48h in freeze drier, is made
The oxidized sodium alginate 13g of the base containing dialdehyde, double percent aldehydes are 48.5%.
Embodiment 5: the preparation of oxidated carboxymethyl cellulose
Carboxymethyl cellulose powder 15g is weighed, is added in 1000ml Erlenmeyer flask, adds water 800ml, stirring and dissolving, with 5%
Aqueous acetic acid tune pH value to pH5.5, oxidant KIO is added48g, sealing are protected from light stirring oxidation reaction 60h at room temperature.
Reaction is finished, and 95% ethanol water of 4 times of volumes is added with stirring, and is precipitated, and sediment filters, with 95% ethanol aqueous wash
It washs 3 times, the oxidated carboxymethyl cellulose 12.1g of the base containing dialdehyde, dialdehyde base percentage is made in dehydrated alcohol dehydration, vacuum drying
Content is 62.5%.
In above-described embodiment 1~5, the oxidation of polysaccharides of the base containing dialdehyde is prepared for using periodate oxidation method.Periodic acid oxygen
Change method can aoxidize a variety of biological polyoses, such as heparin, chondroitin sulfate, sodium alginate, fucoidin, starch, acetic acid
Ester starch and other starch derivatives, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and other celluloses are derivative
Object, chitosan, hydroxyethyl chitosan, hydroxypropyl chitosan, hydroxyl butyl chitosan, succinyl-chitosan, carboxymethyl chitosan and
Other chitosan derivatives, ethoxyl chitin, Hydroxypropyl chitosan, hydroxyl butyl chitin, carboxymethyl chitin and other first
Shell element derivative, hyaluronic acid, guar gum, hydroxypropyl guar gum and other guar derivatives, glucan, dextran, with
And other polysaccharide that those skilled in the art can prepare.Above-mentioned biological polyoses can prepare and contain accordingly through periodate oxidation
There are the oxidation of polysaccharides of dialdehyde base, such as heparin, oxidized chondroitin sulphate, oxidized sodium alginate aoxidizes fucoidin, and oxidation is formed sediment
Powder, acetate starch and other starch derivatives, oxidated carboxymethyl cellulose, oxidation hydroxyethyl cellulose, oxidation hydroxypropyl are fine
Dimension element and other cellulose derivatives, oxidation chitosan, oxidation hydroxyethyl chitosan, oxidation hydroxypropyl chitosan, oxidation hydroxyl fourth
Base enclosure glycan, oxidation succinyl-chitosan, oxidated carboxymethyl chitosan and other chitosan derivatives, aoxidize ethoxy crust
Element, oxidation Hydroxypropyl chitosan, oxidation hydroxyl butyl chitin, oxidated carboxymethyl chitin and other chitin derivativs, oxidation
Hyaluronic acid, oxidized guar, oxidation hydroxypropyl guar gum and other guar derivatives, oxidized dextran, oxidized dextran
Other oxidation of polysaccharides that acid anhydride and those skilled in the art can prepare.Above-mentioned oxidation of polysaccharides base containing dialdehyde, can be used as this hair
The raw material of the bright injection aquagel preparation.
Two, the preparation of injection aquagel
Raw material used in the preparation of the injection aquagel, container, vessel etc. are germ-free condition, and preparation exists
Completed under aseptic condition, it is specific the preparation method is as follows:
1, first dose of hydrogel of preparation
Embodiment 6: first dose of hydrogel preparation 1
Oxidated carboxymethyl cellulose (double aldehyde group contents are 62.5%) 0.5g is weighed, is placed in the glass beaker of 100ml, adds
Enter physiological balance liquid solvent 50ml, stirs lower dissolution, obtain the oxidation of polysaccharides glue that weight percent concentration is 1%, by the glue point
It is fitted into an injection-tube of the sterile Double-body syringe of 10ml specification, first dose of hydrogel is made.
Embodiment 7: first dose of hydrogel preparation 2
Oxidized sodium alginate (double aldehyde group contents are 48.5%) 2.5g is weighed, is placed in the glass beaker of 100ml, nothing is added
Bacterium aqueous solvent 50ml stirs lower dissolution, obtains the oxidation of polysaccharides glue that weight percent concentration is 5%, which is distributed into 10ml
In one injection-tube of the sterile Double-body syringe of specification, first dose of hydrogel is made.
Embodiment 8: first dose of hydrogel preparation 3
Heparin (double aldehyde group contents be 4.2%) 1.5g is weighed, weighing oxidized hyaluronic acid, (double aldehyde group contents are
30.8%) 3.5g is placed in the glass beaker of 100ml, and sterile saline solvent 50ml is added, and is stirred lower dissolution, is obtained weight hundred
Dividing specific concentration is 10% oxidation of polysaccharides glue, which is distributed into an injection of the sterile Double-body syringe of 10ml specification
First dose of hydrogel is made in Guan Zhong.
Embodiment 9: first dose of hydrogel preparation 4
Oxidized chondroitin sulphate (double aldehyde group contents be 2.5%) 0.5g is weighed, weighing oxidized starch, (double aldehyde group contents are
12.5%) 9.5g is placed in the glass beaker of 100ml, and sterile ringer's solution solvent 50ml is added, and is stirred lower dissolution, is obtained weight hundred
Dividing specific concentration is 20% oxidation of polysaccharides glue, which is distributed into an injection of the sterile Double-body syringe of 10ml specification
First dose of hydrogel is made in Guan Zhong.
2, second dose of hydrogel of preparation
Embodiment 10: second dose of hydrogel preparation 1
Collagen 5g is weighed, is placed in the glass beaker of 100ml, sterile aqueous solvent 50ml is added, lower dissolution is stirred, obtains
The collagen glue that concentration expressed in percentage by weight is 10%, is respectively charged into another of the Double-body syringe of 10ml specification for the glue
In injection-tube, second dose of hydrogel is made.
Embodiment 11: second dose of hydrogel preparation 2
Chitin derivativ hydroxypropyl chitosan 7.5g is weighed, is placed in the glass beaker of 100ml, physiological balance liquid is added
Solvent 50ml stirs lower dissolution, obtains the chitin derivativ glue that concentration expressed in percentage by weight is 15%, which is respectively charged into
In another injection-tube of the Double-body syringe of 10ml specification, second dose of hydrogel is made.
Embodiment 12: second dose of hydrogel preparation 3
Chitin derivativ hydroxyethyl chitosan 2g is weighed, collagen 0.5g is weighed, is placed in the glass beaker of 100ml
In, physiological saline solvent 50ml is added, stirs lower dissolution, obtains the chitin derivativ collagen glue that concentration expressed in percentage by weight is 5%
The glue is respectively charged into another injection-tube of the Double-body syringe of 10ml specification by liquid, and second dose of hydrogel is made.
Embodiment 13: second dose of hydrogel preparation 4
Chitin derivativ hydroxyl butyl chitosan 0.2g is weighed, chitin derivativ Hydroxypropyl chitosan 0.3g is weighed, is claimed
Drug rapamycin 0.01g is taken, is placed in the glass beaker of 100ml, sterile aqueous solvent 50ml is added, lower dissolution is stirred, obtains weight
Chitin derivativ/drug glue that percentage concentration is 1% is measured, which is respectively charged into the Double-body syringe of 10ml specification
In another injection-tube, second dose of hydrogel is made.
In the preparation of hydrogel of the present invention, the oxidation of polysaccharides in first dose is the oxidation of polysaccharides of the base containing dialdehyde,
Be further the heparin of the base containing dialdehyde, the oxidized chondroitin sulphate of the base containing dialdehyde, the base containing dialdehyde oxidized sodium alginate, contain
Oxidation fucoidin, the oxidized starch of the base containing dialdehyde, the acetate starch of the base containing dialdehyde and the other starch derivatives of dialdehyde base,
The oxidated carboxymethyl cellulose of the base containing dialdehyde, the oxidation hydroxyethyl cellulose of the base containing dialdehyde, the oxidation hydroxypropyl of the base containing dialdehyde are fine
Dimension element and other cellulose derivatives, the oxidation chitosan of the base containing dialdehyde, the base containing dialdehyde oxidation hydroxyethyl chitosan, contain dialdehyde
The oxidation hydroxypropyl chitosan of base, the oxidation hydroxyl butyl chitosan of the base containing dialdehyde, the base containing dialdehyde oxidation succinyl-chitosan, contain
The oxidated carboxymethyl chitosan and other chitosan derivatives of dialdehyde base, the base containing dialdehyde oxidation ethoxyl chitin, contain dialdehyde
Base oxidation Hydroxypropyl chitosan, the base containing dialdehyde oxidation hydroxyl butyl chitin, the base containing dialdehyde oxidated carboxymethyl chitin and
Other chitin derivativs, the oxidized hyaluronic acid of the base containing dialdehyde, the oxidized guar of the base containing dialdehyde, the base containing dialdehyde oxidation hydroxyl
Propyl guar gum and other guar derivatives, the oxidized dextran of the base containing dialdehyde, the base containing dialdehyde oxidized dextran in
The oxidation of polysaccharides for other bases containing dialdehyde that one or more or those skilled in the art can prepare.The oxidation of the base containing dialdehyde is more
It is 1%~70% that the sugar unit of the base containing dialdehyde, which accounts for the percentage of the total sugar unit of polysaccharide molecule, in sugar；The oxidation of polysaccharides of the base containing dialdehyde exists
Concentration expressed in percentage by weight in glue is 1%~25%, and the solvent in glue is sterile water, physiological saline, physiological balance liquid or ability
Other aqueous medical use liquids that field technique personnel know, such as Glucose Liquid.Chitin derivativ and/or glue in second dose
Former albumen is ethoxyl chitin, Hydroxypropyl chitosan, hydroxyl butyl chitin, carboxymethyl chitin, hydroxyethyl chitosan, hydroxypropyl
One or more of base enclosure glycan, hydroxyl butyl chitosan, carboxymethyl chitosan, succinyl-chitosan or collagen；Crust
The concentration expressed in percentage by weight of plain derivative and/or collagen in glue is 1%~20%, and the solvent in glue is sterile water, life
Manage salt water, physiological balance liquid, or those skilled in the art will know that other aqueous medical use liquids, such as Glucose Liquid.
3, the combination of injection aquagel
Above-described embodiment 6~9 is prepared for first dose of injection aquagel of the present invention, is injection aquagel
Containing oxidation polysaccharide gum liquid it is one.Above-described embodiment 10~13 is prepared for second dose of injection aquagel of the present invention,
It is another dose containing chitin derivativ and/or collagen glue glue of injection aquagel；May be used also in described second dose
Drug is added, the injection aquagel formed is as the intraocular application for using drug carrier.
Embodiment 14: injection aquagel 1
Prepared by first dose of hydrogel prepared by embodiment 7 and embodiment 10 second dose of hydrogel is through Double-body syringe
Fixing piece is combined, and injection aquagel 1 of the present invention is constituted.
Embodiment 15: injection aquagel 2
Prepared by first dose of hydrogel prepared by embodiment 8 and embodiment 11 second dose of hydrogel is through Double-body syringe
Fixing piece is combined, and injection aquagel 2 of the present invention is constituted.
Embodiment 16: injection aquagel 3
Prepared by first dose of hydrogel prepared by embodiment 9 and embodiment 12 second dose of hydrogel is through Double-body syringe
Fixing piece is combined, and injection aquagel 3 of the present invention is constituted.
Embodiment 17: injection aquagel 4
Prepared by first dose of hydrogel prepared by embodiment 6 and embodiment 13 second dose of hydrogel is through Double-body syringe
Fixing piece is combined, and injection aquagel 4 of the present invention is constituted.
Injection aquagel of the present invention is made of two doses of glues, and one is the oxidation of polysaccharides glue of the base containing dialdehyde
Liquid, another dose is the glue containing chitin derivativ and/or collagen, and two doses of glues are respectively charged into two of Double-body syringe
In injection-tube, first dose as injection aquagel of the injection-tube of the oxidation of polysaccharides glue of the base containing dialdehyde is derivative containing chitin
Second dose, first dose and second dose as injection aquagel of the injection-tube of object and/or collagen glue is injected through duplex
Device is injected simultaneously, and two doses of glues mix in bolus infusion processes, is crosslinked, i.e. the dialdehyde base and chitin of oxidation of polysaccharides
The amino of derivative and/or collagen crosslinks reaction, and being formed has viscoelastic hydrogel；May be used also in described second dose
To contain drug, the injection aquagel formed is as the intraocular application for using drug carrier.
Three, application of the injection aquagel as Ocular tamponades
Embodiment 18: injection aquagel is used as Ocular tamponades application in experimental rabbit vitrectomy
The injection aquagel 1 of above-described embodiment 14, the injection aquagel 2 of embodiment 15 are taken, embodiment 16 is infused
Jetting gel 3, the vitrectomy for experimental rabbit are tested.
Experimental animal new zealand rabbit 3 is only respectively labeled as A, B, C, and experimental rabbit female, 2~2.5kg of weight, left eye is art
Eye, right eye are control, preoperative progress slit-lamp, eyeground, intraocular pressure inspection, to determine without eye exception.When operation, routinely dosage
Intramuscular injection chlorpromazine hydrochloride, auricular vein inject yellow Jackets, anesthetized animal, Tropicamide mydriasis, Iodophor periocualr skin
Disinfection, local anesthesia with lidocaine hydrochloride, Ringer's solution is perfusion liquid, carries out triple channel closed type vitrectomy, glass
Gas-liquid exchanges after body excision, and above-mentioned injection aquagel 1, injection aquagel 2, injection aquagel 3 are injected separately into experiment
In the left eye vitreous chamber of rabbit A, B, C, gel is formed in situ, is closed scleral incision.The postoperative drop of tobradex eyedrops 3 times a day
Eye, regular slit lamp observation measure intraocular pressure, eye ultrasound diagnosis, and Ultrasonic pachymetry number evaluates hydrogel in vitreous chamber
Interior filling situation.
Postoperative slit lamp observation situation is shown in Fig. 1, and the postoperative art eye inflammatory reaction of 3 experimental rabbits is slight, and eyeground is high-visible, glass
Keep transparent in glass body 12 weeks, hydrogel is gradually degraded within the eye, and degradation time is greater than 10 weeks.The results are shown in attached figure 2 for intraocular pressure determination,
It can be seen that early postoperation intraocular pressure declines, normal range (NR) is gradually brought to after 10 days.Eye ultrasound diagnosis situation is shown in attached drawing 3, experiment
The ultrasound diagnosis of lagophthalmos portion does not check the acoustic images such as vitreous opacity, bleeding, vitreous-body-retina fibroproliferative, detachment of retina.
Art eye corneal endothelial cell counts amount is shown in Fig. 4, it is seen that art eye corneal endothelium quantity is without being decreased obviously.
Zoopery the result shows that injection aquagel of the present invention is filled into vitreum as Ocular tamponades
It is intracavitary, there is good filling effect, retina can be pressed and be maintained at correct position and keep eyeball shape, in ocular tissue
Compatibility is good, does not influence corneal endothelium quantity and aqueous humor circulation system, and good in optical property does not influence intraocular pressure, do not influence cornea
Endothelium quantity and aqueous humor circulation system, can degrade absorption within the eye, do not need second operation taking-up, be one without toxic side effect
The ideal intraocular vitreum filler of kind, has a vast market foreground.
Injection aquagel of the invention is applied in preparing Ocular tamponades, and injection aquagel is as intraocular medication
Carrier can be such that drug gradually discharges within the eye, reach medication effect, reduce times for spraying, while having good eye
Interior biocompatibility and biological safety, equally have a vast market foreground.
Claims (8)
1. a kind of injection aquagel is preparing the application in Ocular tamponades, it is characterized in that prepared by the injection aquagel
The application of Ocular tamponades in ophthalmologic operation；The injection aquagel is formed by two doses, first dose be the base containing dialdehyde oxygen
Change the glue of polysaccharide, second dose is the glue containing chitin derivativ and/or collagen, and two doses are respectively charged into Double-body syringe
Two injection-tubes in, two doses of glues are injected simultaneously through Double-body syringe, be mixed, be crosslinked in bolus infusion processes, formed tool
There is viscoelastic hydrogel.
2. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that in vitreum
As the application for preparing Ocular tamponades in resection operation.
3. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that in second dose
Also contain drug.
4. injection aquagel as claimed in claim 3 is preparing the application in Ocular tamponades, it is characterized in that as preparation
The intraocular application for using drug carrier.
5. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that described contains
It is 1%~70% that the sugar unit of the base containing dialdehyde, which accounts for the percentage of the total sugar unit of polysaccharide molecule, in the oxidation of polysaccharides of dialdehyde base；Containing dialdehyde
Concentration expressed in percentage by weight of the oxidation of polysaccharides of base in glue is 1%~25%, and the solvent in glue is sterile water, physiological saline or life
Manage equilibrium liquid.
6. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that described contains
The oxidation of polysaccharides of dialdehyde base is the oxidation of the heparin of the base containing dialdehyde, the oxidized chondroitin sulphate of the base containing dialdehyde, the base containing dialdehyde
Sodium alginate, the oxidation fucoidin of the base containing dialdehyde, the oxidized starch of the base containing dialdehyde, the acetate starch of the base containing dialdehyde, containing double
The oxidated carboxymethyl cellulose of aldehyde radical, the oxidation hydroxyethyl cellulose of the base containing dialdehyde, the base containing dialdehyde oxidation hydroxypropyl cellulose,
The oxidation chitosan of the base containing dialdehyde, the oxidation hydroxyethyl chitosan of the base containing dialdehyde, the base containing dialdehyde oxidation hydroxypropyl chitosan, contain
The oxidation hydroxyl butyl chitosan of dialdehyde base, the oxidation succinyl-chitosan of the base containing dialdehyde, the oxidated carboxymethyl shell of the base containing dialdehyde are poly-
The oxidation hydroxyl butyl for aoxidizing ethoxyl chitin, the oxidation Hydroxypropyl chitosan of the base containing dialdehyde, the base containing dialdehyde of sugar, the base containing dialdehyde
Chitin, the oxidated carboxymethyl chitin of the base containing dialdehyde, the oxidized hyaluronic acid of the base containing dialdehyde, the oxidation Guar of the base containing dialdehyde
Glue, the oxidation hydroxypropyl guar gum of the base containing dialdehyde, the oxidized dextran of the base containing dialdehyde, the base containing dialdehyde oxidized dextran in
It is one or more of.
7. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that the first
Shell element derivative be ethoxyl chitin, Hydroxypropyl chitosan, hydroxyl butyl chitin, carboxymethyl chitin, hydroxyethyl chitosan,
One or more of hydroxypropyl chitosan, hydroxyl butyl chitosan, carboxymethyl chitosan, succinyl-chitosan.
8. injection aquagel as described in claim 1 is preparing the application in Ocular tamponades, it is characterized in that the first
The concentration expressed in percentage by weight of shell element derivative and/or collagen in glue is 1%~20%, the solvent in glue be sterile water,
Physiological saline, physiological balance liquid.
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| CN106866841A (en) * | 2017-03-10 | 2017-06-20 | 中国科学院长春应用化学研究所 | A kind of injection aquagel and preparation method thereof |
| CN106822989A (en) * | 2017-03-29 | 2017-06-13 | 青岛辰达生物科技有限公司 | It is a kind of to promote sprayable gel of wound healing and preparation method thereof |
| CN109568657B (en) * | 2017-09-29 | 2021-06-18 | 天津大学 | Use of injectable hydrogels for the preparation of vitreous substitutes |
| CN108434093B (en) * | 2018-06-22 | 2020-02-18 | 青岛大学 | Preparation method of voriconazole intraocular drug controlled-release injectable hydrogel |
| CN109337383B (en) * | 2018-09-30 | 2021-05-25 | 福建工程学院 | Collagen-based self-repairing hydrogel and preparation method thereof |
| CN110404083B (en) * | 2019-07-15 | 2021-03-09 | 浙江工业大学 | Injectable hydrogel material and preparation method and application thereof |
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| CN110628090B (en) * | 2019-10-17 | 2021-06-22 | 陕西科技大学 | Cationic guar gum/chitosan composite hydrogel and preparation method thereof |
| EP4082544A4 (en) * | 2019-12-26 | 2024-01-10 | Santen Pharmaceutical Co., Ltd. | Aqueous suspension composition containing sirolimus or salt thereof |
| CN111012947B (en) * | 2019-12-30 | 2021-11-12 | 南京财经大学 | Injectable and self-healing starch-based hydrogel and preparation method and application thereof |
| CN111228579B (en) * | 2020-01-21 | 2021-12-03 | 赛克赛斯生物科技股份有限公司 | Injectable hydrogel, preparation method and application thereof, and joint lubricant |
| CN111617313B (en) * | 2020-04-29 | 2022-09-06 | 天津医科大学眼科医院 | Application of ophthalmic linear gel in aspect of being used as clinical hole-induced retinal detachment medicine |
| CN113081956A (en) * | 2021-04-12 | 2021-07-09 | 青岛大学附属医院 | Natamycin eye drops modified by oxidized sodium alginate and preparation method thereof |
| CN113827779B (en) | 2021-08-14 | 2022-07-26 | 中国海洋大学 | Biological polysaccharide hydrogel and preparation method and application thereof |
| CN114366853B (en) * | 2022-01-20 | 2023-04-14 | 华东理工大学 | High bone-inducing active dental implant coating and preparation method thereof |
| CN114712550B (en) * | 2022-04-20 | 2023-02-14 | 华中科技大学 | Hydrogel adhesive capable of being injected for rapid hemostasis and preparation method and application thereof |
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