Cataract surgical incision adhesive and preparation method thereof
Technical field
The present invention relates to cataract therapy technical field more particularly to a kind of cataract surgical incision adhesive and its systems
Preparation Method.
Background technology
Cataract is common geriatric disease, is a variety of causes such as aging, heredity, local dystrophia, immune and metabolism
Exception, wound, poisoning, radiation etc. cause crystalline lens metabolic disorder, and crystallins is caused to be denaturalized and are occurred muddy.At present
Cataract is mainly based on ultrasonic emulsification excision treatment, and patient's eye 12 o'clock direction is through fixation through scleral tunnels incision, and Tweezers for eye surgery is by cutting
Mouth removal diseased lens anterior capsule, the crystalline lens of exposure lesion, ultrasonic emulsification remove the crystalline lens of lesion, implantable artificial crystal
Achieve the purpose that treatment.Since preceding aqueous humor oozes out phlyctenular keratoconjunctivitis notch so that anterior chamber's intraocular pressure reduces, and causes Ocular hypotension disease, together
When cataract anterior chamber's notch easily cause the severe complications such as entophthamia, therefore, it is necessary to cataract surgical incision carry out it is closely sealed.
In order to maintain the germ-free condition of intraocular pressure and anterior chamber after cataract operation, clinically it is directed to phlyctenular keratoconjunctivitis at present and cuts
Mouth mainly takes suture to be closed cataract surgical incision with two methods of itself watertight.Watertight method is generally used for folded crystal
Small incision surgery, it is harder that sewing method is generally used for crystal nuclear, the operation of stiff sheet artificial lens.
Since there are many morbidity type of cataract, operation plan is determined according to the different causes of disease, superhard crystal kernel cannot
Carry out cataract surgery treatment, it is necessary to remove lesion kernel, while patient age is larger, economic condition is limited through big notch
In the case of, patient often selects non-collapsible stiff sheet crystal, just big notch must be selected to be treated in performing the operation in this way.For big
Notch, scleral tunnel wider width, it is therefore desirable to carry out suture and be closed cornea wound, to maintain anterior chamber's intraocular pressure and sterile shape
State.Suture is fine to wound adaptation, but since suture meeting corneal affects, cornea rebirth blood vessel,
The complication such as cornea flash of light are more serious, therefore the reference of suture operation method clinic is less.
Watertight method is that the inner valve of operation on cornea notch is pushed away using the pressure of preceding aqueous humor so that inner valve is bonded tightly with outer valve
It is close, so as to achieve the effect that watertight operative incision.But watertight method is stronger for resisting performance perpendicular to the power of cut-out direction,
Poor-performing is resisted to the power of the power in other directions, such as the directions such as eyelid, eye socket, easily causes low pressure eye disease.
Biogum is a kind of method of closely sealed cataract surgical incision just to grow up in recent years, and biogum is mainly by gathering
The substances such as ethylene glycol hydrogel, α hydroxy acrylates are prepared, and are carried out instead using biogum and amino, the hydroxyl in tissue
It should achieve the purpose that wound " suture " by the both ends of operative incision by biological glue bond and one.Biogum is closed to wound
Effect is preferable, can maintain pressure and stable state in front for a long time, but biogum degradation property is poor, and ocular surface is stopped
Stay the time longer, meeting corneal generates additional stimulation, influences the reparation of wound.
Invention content
The purpose of the present invention is to provide a kind of cataract surgical incision adhesive and preparation method thereof, the present invention provides
Adhesive when being used for closely sealed cataract surgical incision, can prevent aqueous humor from flowing out, keep anterior chamber pressure, and be easy to discharge, no
It can corneal generation other influences.
The present invention provides a kind of cataract surgical incision adhesives, are done by chitosan static spinning membrane through vacuum refrigeration
It is dry to obtain.
Chitosan (chitosan) is also known as chitosan, is passed through by the chitin (chitin) that nature is widely present
Cross what deacetylation obtained, chemical name is Chitosan (1-4) -2- amino-B-D glucose.This natural polymer
Biological functionality and the excellent performances such as compatibility, blood compatibility, safety, microbic resolvability closed extensively by all trades and professions
Note, in the numerous areas such as medicine, food, chemical industry, cosmetics, water process, METAL EXTRACTION and recycling, biochemistry and biomedical engineering
Application study achieve major progress.Electrostatic spinning technique (electrostatic spinning, ES) is a kind of simple easy
Capable novel tissue engineering stephanoporate stent preparation method, electrospun material have unique microstructure and appropriate mechanical property
Can, the research and development for biological tissue engineering bracket, slow-release material etc. provide ideal platform.At present people's profit electrostatic spinning technique into
Work(has synthesized the biomaterials such as artificial skin, artificial blood vessel, is prepared using biomaterials such as PLLA, chitosan, collagen, PLGA
The curable product of the functions such as the hemostasis of wound auxiliary material, skin regeneration, targeted drug sustained release.Chitosan-based electrostatic spinning composite wound is auxiliary
Material is the recombination chitosan static spinning membrane that clear layer is prepared using different electrospinning process, and spinning film has lasting
, the antibacterial effect of broad spectrum activity, there is good sustained-release antibacterial and comfort property, describing property of biology is good, and with certain plant
Object fragranced, can be used as medical material, textile garment material, anti-biotic material etc. be widely used in textile industry, medicines and health protection,
The fields such as biomedicine.
The present invention will be used as cataract surgical incision adhesive after chitosan static spinning membrane vacuum freeze drying, shell gathers
Sugared static spinning membrane meets water and forms thick film, has certain viscosity and tension, can prevent aqueous humor from passing through cataract hand
Art wound flows out, and the long period keeps anterior chamber pressure, prevents the appearance of low pressure eye disease.Simultaneously chitosan have it is certain it is anti-inflammatory,
Bacteriostasis prevents wound bacterium infection, reduces the risk of entophthamia.Moreover, chitosan static spinning membrane is water solubility
Film can slowly degrade in cornea, with tear flow out be detached from cornea, without handle remove, will not corneal formed it is secondary
Injury.The experimental results showed that when adhesive provided by the invention is used for closely sealed cataract surgical incision, flow of aqueous humor can be prevented
Go out, anterior chamber pressure can be kept to stablize 1~2 day.
The present invention also provides a kind of preparation method of cataract surgical incision adhesive, including:
By chitosan static spinning membrane vacuum freeze drying.
In the present invention, the chitosan static spinning membrane is prepared in accordance with the following methods:
A) electrostatic spinning will be carried out comprising the spinning solution of chitosan and gelatin, obtains chitosan static spinning membrane;
B) impurity in the chitosan static spinning membrane is removed.
The present invention prepares static spinning membrane using chitosan and gelatin as raw material, wherein, the quality of the chitosan and gelatin
Than being 6~8:2~4, preferably 7:3.The number-average molecular weight of the chitosan is 100,000~500,000.
The present invention in trifluoroacetic acid, then adds in dichloromethane adjustment spinning solution first by chitosan and Gelatin
Then viscosity seals, stood for 24 hours at 4 DEG C.
After standing removes bubble removing, obtained spinning solution is subjected to electrostatic spinning, the parameter of electrostatic spinning is:Front end of the syringe needle
Needle diameter be 0.7mm;The distance between electrostatic spinning machine positive and negative electrode is 7cm~12cm, and positive and negative voltage difference is 20kV
~35kV, the rotating speed of receiver are 100 turns/min~120 turn/min, the translational velocity of electrostatic spinning syringe needle for 0.2mm/s~
0.5mm/s, spinning space temperature are 70 DEG C~90 DEG C, and humidity is 40RH~60RH.Continuous spinning 120min~180min
Obtain chitosan static spinning membrane.
After obtaining chitosan static spinning membrane, impurity therein is removed, specific method is as follows:
It is washed after chitosan static spinning membrane is dried in vacuo with absolute ethyl alcohol, ethyl alcohol is then removed using high-temperature steam.
After the film preparation of chitosan electrostatic spinning is completed, it is dried in vacuo to remove dissolvent residual, is then used
Absolute ethyl alcohol rinses repeatedly, and chitosan static spinning membrane is detached with masking foil;Static spinning membrane is laid in moistening after separation
Cellulose acetate film on be unfolded, utilize high-temperature steam removal ethyl alcohol, you can carry out vacuum freeze drying.
Specifically, can by the chitosan static spinning membrane it is quick-frozen after carry out vacuum freeze drying, it is described quick-frozen
Temperature is -100~-60 DEG C, preferably -80 DEG C.Vacuum freeze drying can remove water extra in chitosan static spinning membrane
Point, the space structure for keeping static spinning membrane certain, so as to be conducive to use as cataract surgical incision adhesive.
After vacuum freeze drying, by chitosan static spinning membrane by ultraviolet disinfection sterilize, be then cut into 3mm ×
5mm rectangular pieces, vacuum packaging store, are spare.
Adhesive provided by the invention can be used for cataract operation fixation through scleral tunnels incision, and it is circumscribed can to close cataract operation
Mouthful, anterior chamber pressure is maintained, suitable for the closely sealed of small notch and big incision cataract surgery corneal incision.
The present invention takes using the chitosan static spinning membrane Jing Guo vacuum freeze drying as adhesive after cataract operation
One fritter chitosan static spinning membrane is attached at operative incision, and chitosan static spinning membrane has certain water solubility, meets water
Thick film is formed, few fibers dissolve to form crisscross fenestral fabric, and drawing wound makes its closure.Simultaneously
Chitosan static spinning membrane has certain acidity, and the stimulation of corneal is smaller, and the chitosan dissolved has certain disappear
The features such as scorching, antibacterial, anti-scar.Chitosan static spinning membrane is preferable to the Adhesion property of wound at the initial stage for attaching wound, right
Wound has preferable sealing effect, with the extension of time, static spinning membrane slowly dissolves, and discharged with tear, at 3 days
It can be removed in time totally, without being removed using processing.
Specific embodiment
In order to further illustrate the present invention, cataract surgical incision provided by the invention is bonded with reference to embodiment
Agent and preparation method thereof is described in detail, but cannot they be interpreted as limiting the scope of the present invention.
Embodiment 1
Chitosan and gelatin that number-average molecular weight is 12w are dissolved according to mass ratio 7: 3 in trifluoroacetic acid solution, slowly
Stirring adds in the dichloromethane solution of trifluoroacetic acid solution volume 30% until completely dissolved, makes a concentration of the 10% of spinning solution,
Solution is sealed after being slowly stirred fully dissolving, it is for use in the bubble that 4 DEG C stand in 24 hours removal solution;
Obtained spinning solution is loaded in syringe, the needle diameter of front end of the syringe needle is 0.7mm, and chitosan is injected
It is positive and negative to adjust electrostatic spinning machine for the syringe needle connection electrostatic spinning machine positive electrode of device, cylinder shape receiver electrostatic spinning machine negative electrode
The distance between electrode is 10cm, and positive and negative voltage difference is set as 110 turns/min in 30kv, the rotating speed of receiver, and chitosan is quiet
The translational velocity of Electrospun syringe needle is 0.3mm/s, and spinning space temperature is 80 DEG C, humidity 50RH.Continuous spinning 160min, system
It is standby to obtain chitosan static spinning membrane;
The chitosan static spinning membrane is subjected to vacuum drying removal residual spin liquid, is then rushed repeatedly with absolute ethyl alcohol
It washes, chitosan static spinning membrane is detached with masking foil, rinse repeatedly after static spinning membrane and static spinning membrane is laid in moistening
Cellulose acetate film on, remove ethyl alcohol using high-temperature steam, be freeze-dried after -80 DEG C of quick freezes, remove Static Spinning
Extra moisture in cortina, the space structure for keeping static spinning membrane certain are stored after disinfection by ultraviolet light processing vacuum packaging, are treated
With.
Obtained static spinning membrane is placed at closely sealed cataract operation fixation through scleral tunnels incision, is initially formed thick thin
Film is discharged after 2 days with tear, and anterior chamber pressure is stablized during use, and aqueous humor does not flow out, and non-corneal generates any influence.
Embodiment 2
Chitosan and gelatin that number-average molecular weight is 25w are dissolved according to mass ratio 7: 3 in trifluoroacetic acid solution, slowly
Stirring adds in the dichloromethane solution of trifluoroacetic acid solution volume 30% until completely dissolved, makes a concentration of the 10% of spinning solution,
Solution is sealed after being slowly stirred fully dissolving, it is for use in the bubble that 4 DEG C stand in 24 hours removal solution;
Obtained spinning solution is loaded in syringe, the needle diameter of front end of the syringe needle is 0.7mm, and chitosan is injected
It is positive and negative to adjust electrostatic spinning machine for the syringe needle connection electrostatic spinning machine positive electrode of device, cylinder shape receiver electrostatic spinning machine negative electrode
The distance between electrode is 7cm, and positive and negative voltage difference is set as 130 turns/min, chitosan electrostatic in 25kv, the rotating speed of receiver
The translational velocity of spinning syringe needle is 0.4mm/s, and spinning space temperature is 70 DEG C, humidity 60RH.It is prepared by continuous spinning 180min
Obtain chitosan static spinning membrane;
The chitosan static spinning membrane is subjected to vacuum drying removal residual spin liquid, is then rushed repeatedly with absolute ethyl alcohol
It washes, chitosan static spinning membrane is detached with masking foil, rinse repeatedly after static spinning membrane and static spinning membrane is laid in moistening
Cellulose acetate film on, remove ethyl alcohol using high-temperature steam, be freeze-dried after -80 DEG C of quick freezes, remove Static Spinning
Extra moisture in cortina, the space structure for keeping static spinning membrane certain are stored after disinfection by ultraviolet light processing vacuum packaging, are treated
With.
Obtained static spinning membrane is placed at closely sealed cataract operation fixation through scleral tunnels incision, is initially formed thick thin
Film is discharged after 2 days with tear, and anterior chamber pressure is stablized during use, and aqueous humor does not flow out, and non-corneal generates any influence.
Embodiment 3
Chitosan and gelatin that number-average molecular weight is 38w are dissolved according to mass ratio 7: 3 in trifluoroacetic acid solution, slowly
Stirring adds in the dichloromethane solution of trifluoroacetic acid solution volume 30% until completely dissolved, makes a concentration of the 15% of spinning solution,
Solution is sealed after being slowly stirred fully dissolving, it is for use in the bubble that 4 DEG C stand in 24 hours removal solution;
Obtained spinning solution is loaded in syringe, the needle diameter of front end of the syringe needle is 0.7mm, and chitosan is injected
It is positive and negative to adjust electrostatic spinning machine for the syringe needle connection electrostatic spinning machine positive electrode of device, cylinder shape receiver electrostatic spinning machine negative electrode
The distance between electrode is 10cm, and positive and negative voltage difference is set as 100 turns/min in 20kv, the rotating speed of receiver, and chitosan is quiet
The translational velocity of Electrospun syringe needle is 0.2mm/s, and spinning space temperature is 70 DEG C, humidity 40RH.Continuous spinning 120min, system
It is standby to obtain chitosan static spinning membrane;
The chitosan static spinning membrane is subjected to vacuum drying removal residual spin liquid, is then rushed repeatedly with absolute ethyl alcohol
It washes, chitosan static spinning membrane is detached with masking foil, rinse repeatedly after static spinning membrane and static spinning membrane is laid in moistening
Cellulose acetate film on, remove ethyl alcohol using high-temperature steam, be freeze-dried after -80 DEG C of quick freezes, remove Static Spinning
Extra moisture in cortina, the space structure for keeping static spinning membrane certain are stored after disinfection by ultraviolet light processing vacuum packaging, are treated
With.
Obtained static spinning membrane is placed at closely sealed cataract operation fixation through scleral tunnels incision, is initially formed thick thin
Film is discharged after 2 days with tear, and anterior chamber pressure is stablized during use, and aqueous humor does not flow out, and non-corneal generates any influence.
Embodiment 4
Chitosan and gelatin that number-average molecular weight is 470,000 are dissolved according to mass ratio 7: 3 in trifluoroacetic acid solution, delayed
Slow stirring adds in the dichloromethane solution of trifluoroacetic acid solution volume 30% until completely dissolved, makes a concentration of of spinning solution
12%, solution is sealed after being slowly stirred fully dissolving, it is for use in the bubble that 4 DEG C stand in 24 hours removal solution;
Obtained spinning solution is loaded in syringe, the needle diameter of front end of the syringe needle is 0.7mm, and chitosan is injected
It is positive and negative to adjust electrostatic spinning machine for the syringe needle connection electrostatic spinning machine positive electrode of device, cylinder shape receiver electrostatic spinning machine negative electrode
The distance between electrode is 12cm, and positive and negative voltage difference is set as 100 turns/min in 35kv, the rotating speed of receiver, and chitosan is quiet
The translational velocity of Electrospun syringe needle is 0.5mm/s, and spinning space temperature is 80 DEG C, humidity 60RH.Continuous spinning 120min, system
It is standby to obtain chitosan static spinning membrane;
The chitosan static spinning membrane is subjected to vacuum drying removal residual spin liquid, is then rushed repeatedly with absolute ethyl alcohol
It washes, chitosan static spinning membrane is detached with masking foil, rinse repeatedly after static spinning membrane and static spinning membrane is laid in moistening
Cellulose acetate film on, remove ethyl alcohol using high-temperature steam, be freeze-dried after -80 DEG C of quick freezes, remove Static Spinning
Extra moisture in cortina, the space structure for keeping static spinning membrane certain are stored after disinfection by ultraviolet light processing vacuum packaging, are treated
With.
Obtained static spinning membrane is placed at closely sealed cataract operation fixation through scleral tunnels incision, is initially formed thick thin
Film is discharged after 2 days with tear, and anterior chamber pressure is stablized during use, and aqueous humor does not flow out, and non-corneal generates any influence.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should
It is considered as protection scope of the present invention.