CN108371729A - There is the viscoelastic agent for ophthalmic surgery and its preparation method and application of radicals scavenging function - Google Patents
There is the viscoelastic agent for ophthalmic surgery and its preparation method and application of radicals scavenging function Download PDFInfo
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- CN108371729A CN108371729A CN201810493133.5A CN201810493133A CN108371729A CN 108371729 A CN108371729 A CN 108371729A CN 201810493133 A CN201810493133 A CN 201810493133A CN 108371729 A CN108371729 A CN 108371729A
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- viscoelastic agent
- mannitol
- sodium hyaluronate
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- 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
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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- 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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- 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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
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- 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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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Abstract
The invention belongs to clinical medicine Ophthalimic microsurgery field of material technology, more particularly to a kind of viscoelastic agent for ophthalmic surgery and its preparation method and application having radicals scavenging function, the viscoelastic agent is mixed by Sodium Hyaluronate and mannitol phosphate buffer, a concentration of 0.1 10wt% of Sodium Hyaluronate in the viscoelastic agent.Viscoelastic agent prepared by the present invention mixes mannitol with Sodium Hyaluronate viscoelastic agent, and the function of its radicals scavenging is assigned while not influencing the physical characteristic of viscoelastic agent itself.
Description
Technical field
The invention belongs to clinical medicine Ophthalimic microsurgery field of material technology, and in particular to one kind having radicals scavenging work(
The viscoelastic agent for ophthalmic surgery and its preparation method and application of energy.
Background technology
Cataract is common blinding eye disease, refer to intraocular crystalline lens occur it is muddy, become opaque by transparent, hinder
Light is hindered to enter intraocular, to affect vision.Cataract operation is to solve this illness most efficient method, and surgical procedure includes
Muddy lens capsule is extractd and artificial lens is put into.One key factor of successful surgery is according to surgical judgement, branch
An ante-chamber with certain depth is overhanged, facilitates insertion into internal oculoscope, while protecting eye inner tissue in surgical procedure.With existing
For the development of medical technology, viscoelastic agent is from last century the eighties as a kind of new cataract operation product ancillary technique
It is used widely in clinical medicine ophthalmologic operation.Viscoelastic agent is that have maintain anterior chamber depth, be conducive to surgical procedure, shielding angle
Film endothelial cell, the high molecular material with defencive function such as prevent intraoperative hemorrhage and separation of synechia, are intraocular lens' implantation
The object of the indispensability of operation can significantly improve the quality of cataract phacoemulsification operation.
Studies have shown that in phacoemulsifica-tion surgical procedure, the tip of probe shakes under ultrasonic frequency oscillation
It is dynamic.Ultrasonic wavelength passes through aqueous humor, generates small air bubble, expansion and implosion release energy and heat.Energy and heat
The generation of release excitation free radical, may damage endothelial cell.Hydrogen peroxide (H2O2) extremely low water is in usually in aqueous humor
Flat place (0.025mM).And have it is demonstrated experimentally that Human Umbilical Vein Endothelial Cells have acute toxicity and cause when hydrogen peroxide level is higher than 0.3mM
Corneal edema.
Commercially available ophthalmology viscoelastic agents most of now are the gel products with Sodium Hyaluronate (SH) for raw material,
Sodium Hyaluronate (SH) has radicals scavenging effect.However, Sodium Hyaluronate (SH) can be adjoint to the cleaning reaction of free radical
The reduction for its molecular weight reduces corneal endothelium protective effect.Developing a kind of can efficiently remove the viscous of free radical
Bullet agent has prodigious medical value.
Mannitol also known as D-mannital, molecular formula C6H14O6, molecular weight 182.17 is a kind of familiar hexa-atomic
Alcohol is isomer with sorbierite.Mannitol is a kind of non-hygroscopic, odorless, white or colourless crystalline powder.Mannitol without
Pharmacological activity, also seldom metabolism, is not easy to enter tissue by capillary in human body.To after internal injection mannitol,
Mannitol molecule can only flow in the blood vessels, and tissue is made to generate osmotic gradient with intravascular system, and liquid is promoted to be flowed to from tissue
Blood vessel improves rapidly plasma osmolarity, so that moisture excessive in tissue is shifted to blood plasma, is then discharged by kidney excretion system
In vitro, have the function that diuresis drains.In addition, mannitol is also free radical street cleaner, can effectively restraint of liberty base to skin
Oxidative demage power, tissue free radical reduce after injection to the degradation of product it is red and swollen react, slow down the drop of gel molecular
Solution, keeps curative effect more lasting.
Chinese patent CN104771331A discloses a kind of hyaluronic acid elastomer, mainly by hyaluronic acid and crosslinking
Agent is reacted, so as to become ophthalmology viscoelastic agent.However this viscoelastic agent do not disclose have the function of remove free radical.
Invention content
Invention broadly provides a kind of viscoelastic agent for ophthalmic surgery having radicals scavenging function and preparation method thereof and answer
With mannitol is mixed with Sodium Hyaluronate viscoelastic agent, is assigned while not influencing the physical characteristic of viscoelastic agent itself
The function of its radicals scavenging.Its technical solution is as follows：
A kind of viscoelastic agent for ophthalmic surgery having radicals scavenging function, by Sodium Hyaluronate and mannitol phosphate-buffered
Liquid mixes, a concentration of 0.1-10wt% of Sodium Hyaluronate in the viscoelastic agent.
Preferably, the mass concentration of mannitol is 0.05-2.0% in mannitol phosphate buffer.
A kind of preparation method of the above-mentioned viscoelastic agent for ophthalmic surgery for having a radicals scavenging function, includes the following steps：
(1) it takes mannitol solid to be dissolved in phosphate buffer, obtains the mannitol phosphoric acid of a concentration of 0.05-2.0wt%
Salt buffer passes through membrane filtration；
(2) Sodium Hyaluronate dry powder is weighed, is dissolved in mannitol phosphate buffer, stand at low temperature obtains Sodium Hyaluronate
The sodium hyaluronate solution of a concentration of 0.1-10wt%；
(3) by sodium hyaluronate solution autoclave sterilization to get the ophthalmologic operation viscoelastic with radicals scavenging function
Agent.
Preferably, the aperture of filter membrane is 0.22 μm in step (1).
Application of the above-mentioned viscoelastic agent in the protection of operated eye corneal endothelium.
Using the above scheme, the present invention has the following advantages：
Viscoelastic agent of the present invention mixes mannitol with Sodium Hyaluronate viscoelastic agent, in the object for not influencing viscoelastic agent itself
The function of its radicals scavenging is assigned while managing characteristic.It can be in the middle reduction phacoemulsifica-tion of cataract operation
Phenomena such as free radical injury in the process, the effectively damage of reduction endothelial cell and red and swollen cornea, surgical quality is improved, is subtracted
Few endothelial cell radical damage, corneal endothelium have good protective effect.
Description of the drawings
Fig. 1 is containing mannitol and the hyaluronic acid sodium gel dynamic viscosity comparison diagram for not containing mannitol.
Specific implementation mode
It weighs mannitol solid and is dissolved in phosphate buffer (pH7.2), be configured to a concentration of 0.05-2%'s (w/v)
Then solution uses 0.22 μm of membrane filtration, stand at low temperature for use.Sodium Hyaluronate dry powder is dissolved in prepared slow
In fliud flushing solution, it being configured to the gel solution of a concentration of 1.0-2.5% (w/v), stand at low temperature is until be uniformly dissolved, and then 121
DEG C autoclave sterilization 15min, is prepared into the Sodium Hyaluronate viscoelastic agent with radicals scavenging function.
Experimental method in following embodiment is conventional method unless otherwise required, involved experiment reagent and material
Material is conventional biochemical reagent and material unless otherwise required.
Embodiment 1
Weigh mannitol solid 1.00g, be dissolved in the phosphate buffer of 100mL, be configured to a concentration of 1% contain sweet dew
Alcohol buffer solution, and pass through 0.22 μm of membrane filtration.2.0g Sodium Hyaluronate dry powder is weighed respectively, is dissolved in containing mannitol and is free of
In the phosphate buffer of mannitol, it is configured to the hyaluronic acid sodium gel solution of a concentration of 20mg/mL.
Embodiment 2
Weigh mannitol solid 0.50g, be dissolved in the phosphate buffer of 100mL, be configured to a concentration of 0.5% containing sweet
Reveal alcohol buffer solution, and passes through 0.22 μm of membrane filtration.2.0g Sodium Hyaluronate dry powder is weighed, is dissolved in containing mannitol and without sweet
In the phosphate buffer for revealing alcohol, it is configured to the hyaluronic acid sodium gel solution of a concentration of 20mg/mL.
Embodiment 3
Weigh mannitol solid 0.20g, be dissolved in the phosphate buffer of 100mL, be configured to a concentration of 0.2% containing sweet
Reveal alcohol buffer solution, and passes through 0.22 μm of membrane filtration.2.0g Sodium Hyaluronate dry powder is weighed, is dissolved in containing mannitol and without sweet
In the phosphate buffer for revealing alcohol, it is configured to the hyaluronic acid sodium gel solution of a concentration of 20mg/mL.
Embodiment 4
Using the buffer solution containing 0.5% mannitol as solvent, the sodium hyaluronate solution of 20mg/mL is prepared, 121 DEG C, is sterilized
15min, sampling 0.5mL are performed a scan using TA AR2000CX rheometers at 0.001-100HZ.It uses simultaneously《China
Pharmacopeia version in 2015》0633 the second method of viscosimetry of general rule tests sample.
1 viscosity test results of table
Embodiment 5
1, hydroxyl radical free radical method surveys the viscoelastic agent of ophthalmology containing mannitol and mannitol and hyaluronic acid viscoelastic agent radicals scavenging
Ability, test philosophy are as follows：
Under ferrous ion effect, hydrogen peroxide generates hydroxyl radical free radical, and salicylic acid is added and captures the hydroxy radical generated,
Purple product is generated, product has characteristic absorption in visible region.In the presence of having antioxidant, it will be competed with salicylic acid and capture hydroxyl
Free radical makes purple product reduce, and absorbance changes.By comparing the variation of absorbance, the antioxidant activity of determinand is evaluated.
Method：6mmol/LFeSO is taken respectively4Solution 2mL, sample liquid 2mL, 6mmol/LH2O2Solution 2mL stands 10min
Afterwards, 6mmol/L salicylic acid solution 2mL are added, after standing 30min, absorbance is surveyed at wavelength 510nm.Blank control is distilled
Water replaces sample liquid, remaining is constant.
In formula：
A0For the absorbance of blank control；
A1For the absorbance of certain mass concentration sample liquid；
A2For no salicylic acid when sample liquid absorbance.
2, hydroxyl radical free radical method to embodiment 1,2,3 prepare containing mannitol buffer, hyaluronic acid sodium gel and containing
The hyaluronic acid sodium gel of mannitol is tested.Test result is as follows：
2 hydroxyl radical free radical method sample free radical scavenging ability of table
As seen from Table 2, mannitol has good hydroxyl radical free radical elimination effect, and the higher elimination effect of concentration is more
It is good.Hyaluronic acid sodium gel also has certain free radical scavenging ability, the hyaluronic acid sodium gel free radical containing mannitol
Removing function has synergistic effect.
Embodiment 6
1, rabbit cornea endothelial tissue damage model is established, cornea is passed through in the eyes of animal by a 30G syringe needle
Edge takes out about 100 milliliters of aqueous humor, and ophthalmology viscoelastic agent is injected above-mentioned position and is filled completely；It waits for one minute, passes through 20G syringe needles
It is inserted into flushing/suction casing, cleaning down is carried out with physiological saline.Inject the 100 certain density H of μ L2O2Physiology is used in combination in solution
Brine filling remaining anterior chamber region, control group saline injection, animal conservation narcosis put to death materials after lower 5 hours.It is right
Cornea tissue carries out annular bore materials, and Janus green decoration methods test corneal endothelial tissue degree of injury.
This method allows to be influenced to carry out quantitative test by the oxidative deformation of irreversible procedure on exposed endothelial cell.
Janus green dyestuffs can purposefully dye without dyeing reactive endothelial cells deformed region.It uses endothelial cell side
The 1%Janus green dye solutions (Sigma) of 200 μ L are incubated 90 seconds.It is with physiology of balance brine that free dye is thin from epidermis
2min removals are rinsed on born of the same parents, and trepan materials then are carried out to cornea.
The dyestuff combined with endothelial cell is detached from by impregnating 90s in 1ml absolute alcohols from cornea tissue, by band
There is the alcoholic solution of Janus green dyestuffs to carry out ten times of dilutions.The alcohol sample that Janus green dyestuffs remove is diluted
It is 10%, photometric measurement is carried out with spectrophotometer.
2, purpose：Using rabbit as subjects, rabbit cornea endothelial tissue damage model is established, carries out radical scavenging activity
Power zoopery effect observation
Sample：Hyaluronic acid sodium gel sample prepared by embodiment 1,2,3 and the hyaluronic acid sodium gel sample containing mannitol
Product.
Animal：Healthy new zealand white rabbit 20.
Experimental implementation：The hyaluronic acid sodium gel that rabbit cornea endothelial tissue damage model prepares embodiment 1,2,3 with
And the hyaluronic acid sodium gel containing mannitol is tested, H2O2Using 10mM concentration.Normal saline buffer solution as a control group,
Every group of five rabbits, totally 10 glasses, viscoelastic agent is replaced as a control group with physiological saline equilibrium liquid, for 100% injury.Experiment
As a result as follows：
2 zoopery endothelial injuries situation of table is evaluated
Results of animal is shown, is added to the hyaluronic acid sodium gel of mannitol to using independent hyaluronic acid sodium gel
Corneal endothelium has stronger effect.
Embodiment 7
The experimental study that the addition of mannitol influences Sodium Hyaluronate viscoelastic agent performance
Respectively using phosphate buffer and containing 0.5% mannitol phosphate buffer as solvent, 20mg/mL concentration is prepared
Sodium hyaluronate solution, and performed a scan at 0.001-100HZ using TA AR2000CX rheometers.Frequency scanning
As a result (Fig. 1) is shown, the rheological properties and viscoelastic property for adding the hyaluronic acid sodium gel after mannitol properly increase.Together
When to containing and the hyaluronic acid sodium gel sample without mannitol carries out test discovery, the Sodium Hyaluronate for adding mannitol is solidifying
Glue intrinsic viscosity also increases.Therefore, this same hyaluronic acid sodium gel of ophthalmology viscoelastic agent with radicals scavenging function
As effect in ophthalmologic operation, endothelial cell can be effectively protected from damage.
It will be apparent to those skilled in the art that technical solution that can be as described above and design, make various other
Corresponding change and deformation, and all these changes and deformation should all belong to the protection domain of the claims in the present invention
Within.
Claims (5)
1. a kind of viscoelastic agent for ophthalmic surgery having radicals scavenging function, by Sodium Hyaluronate and mannitol phosphate buffer
It mixes, a concentration of 0.1-10wt% of Sodium Hyaluronate in the viscoelastic agent.
2. the viscoelastic agent for ophthalmic surgery according to claim 1 for having radicals scavenging function, it is characterised in that：Mannitol phosphorus
The mass concentration of mannitol is 0.05-2.0% in phthalate buffer.
3. a kind of preparation method of the as described in claim 1 viscoelastic agent for ophthalmic surgery for having a radicals scavenging function, feature
It is：Include the following steps：
(1) mannitol solid is taken to be dissolved in phosphate buffer, the mannitol phosphate for obtaining a concentration of 0.05-2.0wt% is slow
Fliud flushing passes through membrane filtration；
(2) Sodium Hyaluronate dry powder is weighed, is dissolved in mannitol phosphate buffer, stand at low temperature obtains hyaluronic acid na concn
For the sodium hyaluronate solution of 0.1-10wt%；
(3) by sodium hyaluronate solution autoclave sterilization to get the viscoelastic agent for ophthalmic surgery with radicals scavenging function.
4. the preparation method of the viscoelastic agent for ophthalmic surgery according to claim 3 for having a radicals scavenging function, feature exist
In：The aperture of filter membrane is 0.22 μm in step (1).
5. application of the viscoelastic agent described in claim 1 in the protection of operated eye corneal endothelium.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1938056A (en) * | 2004-03-29 | 2007-03-28 | 博士伦公司 | New free-radical scavenger containing viscoelastic composition, methods of use and package |
| CN104083396A (en) * | 2014-06-27 | 2014-10-08 | 牟国营 | Corneal surface protectant as well as preparation method and application thereof |
-
2018
- 2018-05-22 CN CN201810493133.5A patent/CN108371729A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1938056A (en) * | 2004-03-29 | 2007-03-28 | 博士伦公司 | New free-radical scavenger containing viscoelastic composition, methods of use and package |
| CN104083396A (en) * | 2014-06-27 | 2014-10-08 | 牟国营 | Corneal surface protectant as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 韦新建: "甘露醇清除自由基治疗脑梗死61例疗效观察", 《中国社区医师(医学专业)》 * |
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