CN105749360B - A kind of composition and the preparation method and application thereof for protecting cornea - Google Patents
A kind of composition and the preparation method and application thereof for protecting cornea Download PDFInfo
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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
- A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
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- A—HUMAN NECESSITIES
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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
- 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
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- 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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Abstract
The invention discloses a kind of composition and the preparation method and application thereof for protecting cornea, main component is solid moisturizing Lubrication Composition, liquid moisturizing Lubrication Composition, osmotic pressure modifying ingredients and water.Composition of the invention uses dual moisturizing Lubrication Composition --- solid moisturizing Lubrication Composition and liquid moisturizing Lubrication Composition, makes the composition more favorably sprawling and be detained in anterior corneal surface, preferably protection corneal epithelium, avoids being damaged because of drying.For the preparation process of the present composition it is not necessary that solution to be heated to boiling, preparation manipulation is simpler, without refrigeration when manufacturing cycle is less than 48h, transport and storage, reduces transport and use cost.
Description
Technical field
The present invention relates to ophthalmologic operation field of medical article technology, more particularly to a kind of composition for protecting cornea and
Preparation method and application.
Background technique
In examination of eyes and ophthalmologic operation, corneal exposure loses the protection of tear in the external world, can due to dry by
Damage.Clinical solution is frequently to use physiological saline or commercially available viscous in anterior corneal surface in inspection and operation mostly at present
Bullet agent.However since physiological saline is shorter in the anterior corneal surface residence time, need to frequently it use, this allows for operation interruption, to facing
Bed doctor makes troubles, and in addition physiological saline also brings discomfort to patient using can excessively make sufferer eye swelling.And viscoelastic agent
It is poor in anterior corneal surface dispersibility due to more sticky, protective layer cannot be quickly formed, it is needed to wait for and is uniformly dispersed, or again
When instillation viscoelastic agents, interruption or bubble are had between the viscoelastic agent that successively instils, the cornea that adequately protects cannot be played the role of,
The visual field can be made unintelligible, made troubles to clinical manipulation.
It is other to disclose for protecting the product of cornea there is also many defects, it is special such as Publication No. CN102225220A
A kind of viscoelastic agent for ophthalmic surgery is disclosed in benefit application, is that Sodium Hyaluronate and hydroxypropyl methylcellulose are dissolved in phosphate respectively to delay
It in fliud flushing, then mixes, filters, sterilizes, dispenses.The viscoelastic agent is injected into during surgery in postcorneal anterior chamber,
It plays a supporting role, is convenient for surgical procedure, therefore viscosity and elasticity require higher, can just play the role of supported anterior chamber, but
It is the problem of viscosity higher position certainly exists bad dispersibility.In addition, the main component Sodium Hyaluronate in the product is needed in low temperature
Under the conditions of save, otherwise property is unstable, it may occur that rotten；Due to can not high-temperature sterilization, clump count and endogenous toxic material therein
Cellulose content is unable to get effective control, is used for ophthalmologic operation, will increase the risk of infection.It is needed in the preparation process of the product
Buffer is heated, have moisture that can evaporate, so that osmotic pressure will change, subsequent component (Sodium Hyaluronate)
It is added, can also cause the variation of osmotic pressure, it is final not larger with environment seepage pressure difference using the product in anterior chamber, at this moment it can draw
Body tissue adverse reaction is played, such as swollen tissue or dehydration.
A kind of intraocular note dilution of improvement is disclosed in the patent application of Publication No. TWI290050, with hand within the eye
During art, for reducing injury of the drying condition to eye inner tissue, which is mainly with hydroxypropyl methyl cellulose
Viscosity and surface tension modifying agent are regulator using other inorganic salts.With the viscoelastic agent for ophthalmic surgery in CN102225220A
Similar, which is also used for inside eyeball, and viscosity and elasticity require higher, however it remains the problem of bad dispersibility.
A kind of anterior corneal surface protective agent is disclosed in the patent application of Publication No. CN104083396, the product is by transparent
Matter acid sodium or chondroitin sulfate or chitosan and buffer composition.Wherein Sodium Hyaluronate, constituent of chitosan cost of material are higher；
And it is unstable under product high temperature, transport and storage need to refrigerate；So that reduce particle number, clump count and endotoxin content means without
Method on these substances, make its cleanliness be not readily reachable by operation with require.
Although prior art discloses the products for eye of a variety of Lubrication Compositions containing moisturizing, but still without a kind of production
Product can meet simultaneously the following conditions: moisturizing greasy property is good, and in anterior corneal surface good dispersion property, constitutive property is stablized,
Clump count, particle number, endotoxin content are easy to reach operation requirement.
Summary of the invention
The purpose of the present invention is being directed to technological deficiency existing in the prior art, in a first aspect, providing a kind of with good
The composition of the protection cornea of moisturizing lubrication and dispersion effect, main component are solid moisturizing Lubrication Composition, liquid moisturizing profit
Sliding ingredient, osmotic pressure modifying ingredients and water；Wherein, the content of each main component are as follows: the 0.05%-10% based on mass percentage
Solid moisturizing Lubrication Composition, 0.1%-55% liquid moisturizing Lubrication Composition, 0.8%-1.4% osmotic pressure modifying ingredients and surplus
Water.
The solid moisturizing Lubrication Composition mass percentage preferred 0.1%-5%, 1%-2%, 1%-3% or 1%-
4%；Liquid moisturizing Lubrication Composition mass percentage preferred 10%-45%, 10%-55%, 10%-25% or 10%-40%；
Osmotic pressure modifying ingredients mass percentage preferred 1%-1.2%, 0.83%-1%, 0.9%-1.4% or 1%-1.4%.?
That is when solid moisturizing Lubrication Composition mass percentage is selected from 0.1%-5%, liquid moisturizing Lubrication Composition quality percentage
Content can be 10%-45%, 10%-55%, 10%-25% or 10%-40%, osmotic pressure modifying ingredients mass percentage
It can be 1%-1.2%, 0.83%-1%, 0.9%-1.4% or 1%-1.4%；And so on.When liquid moisturizing Lubrication Composition
When mass percentage is selected from 10%-45%, solid moisturizing Lubrication Composition mass percentage can be 0.1%-5%, 1%-
2%, 1%-3% or 1%-4%, osmotic pressure modifying ingredients mass percentage can be 1%-1.2%, 0.83%-1%,
0.9%-1.4% or 1%-1.4%；And so on.
The solid moisturizing Lubrication Composition can for hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose,
The combination of one or more of carragheen and carbomer, preferably hydroxypropyl methyl cellulose, sodium carboxymethylcellulose and Ka Bo
One or more of nurse.
The available nominal viscosity of hydroxypropyl methyl cellulose be 6,15,50,100,250,750,1500,4000,
One or more of 10000 and 15000mPas, one of preferably 15,50,100,250,750 and 1500mPas or
It is several；High viscosity can be selected in the sodium carboxymethylcellulose, and (range of viscosities of the sodium carboxymethylcellulose concentration in 1wt% be
1000-4500mPas), medium viscosity (range of viscosities when sodium carboxymethylcellulose concentration 2wt% is 300-3100mPas)
Or (range of viscosities of concentration is 25-100mPas) to low viscosity when sodium carboxymethylcellulose 2wt%, preferably medium viscosity or low viscous
Degree；The available average molecular weight of hydroxypropyl cellulose is 80000,95000,140000,370000,850000 and
One or more of 1150000, one or more of preferably 80000,95000,140000 and 370000；The carragheen
It is preferred that medical rank；Carbomer 910, carbomer 934, Acritamer 940, Carbopol 941, preferably card wave can be selected in the carbomer
Nurse 934 and Acritamer 940.
The liquid moisturizing Lubrication Composition can be in glycerine, polyethylene glycol-400, polyethylene glycol -300 and propylene glycol one
Kind or several combinations, preferably at least one of glycerine, polyethylene glycol-400 and propylene glycol.
The osmotic pressure modifying ingredients is the substance that can make the composition osmotic pressure 295-305mOsmol/kg；
The osmotic pressure modifying ingredients can be selected from sodium chloride, potassium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, gluconic acid
The one or more combination of zinc, lactic acid；
The following substance of the final concentration (w/w) of the osmotic pressure modifying ingredients preferably in the composition: sodium chloride
(NaCl) 0.505%-0.710%, potassium chloride (KCl) 0%-0.021%, sodium dihydrogen phosphate (NaH2PO4) 0.052%-
0.142%, potassium dihydrogen phosphate (KH2PO4) 0.027-0.166%, zinc gluconate 0-0.5% and lactic acid 0-0.01%.
Second aspect provides the method for preparing above-mentioned composition, and osmotic pressure modifying ingredients is dissolved in after water dissolution and is filtered out excessively
Bacterium obtains osmotic pressure and adjusts solution；Adsorption treatment liquid moisturizing Lubrication Composition, obtains liquid moisturizing lubrication solution；Solid is protected
Wet Lubrication Composition is slowly added to osmotic pressure one by one and adjusts in solution and evenly dispersed at uniform solution, adds liquid moisturizing lubrication
Solution adjusts infiltration with saturated sodium chloride solution or physiological saline and is depressed into 295-305mOsmol/kg, and swelling overnight, is crossed and filtered out
Bacterium.
The following steps are included:
1) weighs osmotic pressure modifying ingredients soluble in water to be configured to salting liquid (preferably final concentration of in the composition
The sodium chloride (NaCl) of 0.505wt%-0.710wt%, the potassium chloride (KCl) of 0wt%-0.021wt%, 0.052wt%-
Sodium dihydrogen phosphate (the NaH of 0.142wt%2PO4), the potassium dihydrogen phosphate (KH of 0.027wt%-0.166wt%2PO4), 0wt%-
The zinc gluconate of 0.5wt% and the lactic acid of 0wt%-0.01wt%), after crossing 0.22 μm of filter membrane, 121 DEG C of steam sterilizing 30min,
It obtains osmotic pressure and adjusts solution；
2) weighs at least one of liquid moisturizing Lubrication Composition, respectively with active carbon is removed after activated carbon adsorption, mixes
Obtain liquid moisturizing lubrication solution；It is another to prepare the sodium chloride solution that sodium chloride mass percentage is 26.5wt%, 121 DEG C of steam
Sterilize 30min；
3) solid moisturizing Lubrication Composition is slowly added to osmotic pressure under 65 ± 5 DEG C, stirring condition one by one and adjusts solution by
In, evenly spread out to solid moisturizing Lubrication Composition to be formed uniform solution (if solid moisturizing Lubrication Composition more than one, first plus
Enter it is a kind of it is evenly dispersed at uniform solution after, then plus it is another, and so on) after, add the liquid moisturizing that step 2) obtains
Lubrication solution stirs 30min, adjusts infiltration with the sodium chloride solution or physiological saline of 26.5wt% and is depressed into 295-305mOsmol/
Kg obtains solution A；
4) solution A that step 3) obtains is swollen (> 12h) overnight at room temperature and obtains solution B by, successively 0.8 μm excessively,
0.5 μm, 0.3 μm of filter membrane filters pressing；
5) liquid after step 4) filters pressing is placed in 121 DEG C of steam sterilizing 30min in steam sterilization pan by, after steam sterilizing
Stirring, obtains clear homogeneous viscous liquid；Sufficient standing arrives the composition of the protection cornea to bubble-free.
The third aspect provides the composition for the protection cornea that the above method is prepared, viscosity 350mPas-
500mPas, endotoxin content < 0.5EU/mL, the particle number that 10 μm of transmitance > 99%, > are micro- less than 25 μm of 600, >
Grain number is less than 15.
Fourth aspect, provides application of the above-mentioned composition in the drug that preparation avoids bitot's patches, and the drug is drop
Eye agent, irrigation or liniment.
Compared with prior art, the beneficial effects of the present invention are:
The present invention protects the composition of cornea to use dual moisturizing Lubrication Composition --- solid moisturizing Lubrication Composition and liquid
Moisturizing Lubrication Composition is more conducive to the composition in cornea table by assembling to two kinds of moisturizing Lubrication Composition type and content
Sprawling and being detained for face, can quickly form a protective layer in anterior corneal surface, will not generate bubble or section when successively instiling, thoroughly
Light rate is well beyond clinical demand, to guarantee the clarity of better moisturizing lubricity and visual area, preferably protects cornea
Epithelial layer avoids being damaged because of drying.The composition is guaranteed in final products by the regulation to osmotic pressure modifying ingredients
Osmotic pressure is essentially identical with artificial tears, is 295-305mOsmol/kg (pH are as follows: 6.5-7.5).It is each in composition of the invention
Constitutive property is stablized, and is not influenced by low temperature or high temperature, can be pacified by the inspection of the safety indexs such as sterile, endotoxin, particle
Completely without side effect, clinical patients can be safe to use；Each component can participate in body metabolism and be carried in vitro with excrement, be not required to it
He rinses or the operation of removal, will not cause discomfort, the adverse reaction of sufferer；Low cost of raw materials will not give sufferer band
Carry out financial burden, it can be by big well-established.In addition, the preparation process of the present composition is made it is not necessary that solution to be heated to boiling
Standby operation is simpler, without refrigerating when manufacturing cycle is less than 48h, transport and storage, reduces transport and use cost.
Specific embodiment
The invention proposes one kind in examination of eyes or ophthalmologic surgical procedures institute's exposure angle film in need or bitot's patches
In the case where be used to protect the composition of corneal epithelium.The composition presses mass percentage, including 0.15wt%-65wt%
Moisturizing Lubrication Composition, 0.8wt%-1.4wt% osmotic pressure modifying ingredients and surplus water.Moisturizing Lubrication Composition therein by
0.05wt%-10wt% solid moisturizing Lubrication Composition and 0.1wt%-55wt% liquid moisturizing Lubrication Composition composition.
Solid moisturizing Lubrication Composition can be hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, card
One or more in glue and carbomer are drawn, mixed proportion is unlimited, preferably one of hydroxypropyl methyl cellulose and carbomer
Or two kinds.
Hydroxypropyl methyl cellulose is as the principle active component in the present composition, first is that providing properly for composition
Viscosity, make it have adhesiveness, meet in surgical procedure it is required dispersibility and the residence time require；Second is that wetting enough
And lubrication, making anterior corneal surface, boundary is not dry and cause to damage due to exposure；Third is that safety, will not bring any peace for patient
Full hidden danger.Sodium carboxymethylcellulose has moisture retention, and aqueous solution adheres to anterior corneal surface and forms protective layer.Present invention combination
The content of sodium carboxymethylcellulose and hydroxypropyl methyl cellulose is directly related to the viscosity of composition in object, and then influence
It is clinical applicability；Too high levels, then viscosity is big, and slowly, clinical manipulation is inconvenient for dispersion；Content is too low, then viscosity is low, cannot
Meet the requirement of clinical operation residence time.
In the present invention hydroxypropyl methyl cellulose select nominal viscosity be 6,15,50,100,250,750,1500,4000,
The combination of one or more of 10000 and 15000mPas, in preferably 15,50,100,250,750 and 1500mPas
One or more of combinations；High viscosity (sodium carboxymethylcellulose concentration viscosity model in 1wt% can be selected in sodium carboxymethylcellulose
Enclose that (sodium carboxymethylcellulose concentration range of viscosities in 2wt% is 300- for 1000-4500mPas), medium viscosity
3100mPas) or three kinds of low viscosity (sodium carboxymethylcellulose concentration in 2wt% range of viscosities be 25-100mPas), excellent
Choose viscosity or low viscosity；The average molecular weight of hydroxypropyl cellulose is 80000,95000,140000,370000,850000 and
One or more of 1150000 combination, the group of one or more of preferably 80000,95000,140000 and 370000
It closes.
OK a karaoke club glue solution has certain viscosity, can increase the viscosity of composition itself, it may have stronger water-retaining property.Card
Wave nurse can adhere to anterior corneal surface, form liquid reservoir in eyeball surface, to keep eye wet.Carbomer can increase in eye
The adhesion and retention time of ball surface are about 2 hours in the residence time of eye, can be selected carbomer 910, carbomer 934,
The combination of one or more of Acritamer 940 and Carbopol 941, preferably carbomer 934 and Acritamer 940.
Liquid moisturizing Lubrication Composition can be a kind of in glycerine, polyethylene glycol-400, polyethylene glycol -300 and propylene glycol
Or it is several, mixed proportion is unlimited, preferably one or more of glycerine, polyethylene glycol-400 and propylene glycol.
What glycerine, polyethylene glycol-400, polyethylene glycol -300 and propylene glycol in the present composition rose is that moisturizing is made
With.Wherein glycerine viscosity is larger, and polyethylene glycol-400, polyethylene glycol -300 and propylene glycol viscosity are smaller, can assemble
The dispersibility and transparency of common regulation composition.
Osmotic pressure modifying ingredients is contained the following substances by final mass percentage composition in the composition: sodium chloride (NaCl)
0.505%-0.710%, potassium chloride (KCl) 0%-0.021%, sodium dihydrogen phosphate (NaH2PO4) 0.052%-0.142%, phosphoric acid
Potassium dihydrogen (KH2PO4) 0.027-0.166%, zinc gluconate 0-0.5% and lactic acid 0-0.01%.
Water used in the present composition is water for injection, as distilled water or the distillation resulting water of deionized water.
The method for preparing above-mentioned composition, comprising the following steps:
1) weighs the osmotic pressure modifying ingredients salting liquid soluble in water that is configured to and (contains in salting liquid by mass percentage
Following substance: sodium chloride (NaCl) 0.505%-0.710%, potassium chloride (KCl) 0%-0.021%, sodium dihydrogen phosphate
(NaH2PO4) 0.052%-0.142%, potassium dihydrogen phosphate (KH2PO4) 0.027-0.166%, zinc gluconate 0-0.5% and cream
Sour 0-0.01%), after crossing 0.22 μm of filter membrane, 121 DEG C of steam sterilizing 30min obtain osmotic pressure and adjust solution；
2) crosses film after weighing liquid moisturizing Lubrication Composition activated carbon adsorption, obtains liquid moisturizing lubrication solution (if liquid
There are many moisturizing Lubrication Compositions, is mixed to get after removing active carbon with every kind of liquid moisturizing Lubrication Composition of activated carbon adsorption respectively
Liquid moisturizing lubrication solution)；Prepare the sodium chloride solution that sodium chloride mass percentage is 26.5wt%, 121 DEG C of steam sterilizings
30min；
3) under the conditions of 65 ± 5 DEG C while stirring by solid moisturizing Lubrication Composition be slowly added to one by one osmotic pressure adjust it is molten
In liquid, be uniformly dispersed to solid moisturizing Lubrication Composition to be formed uniform solution (if solid moisturizing Lubrication Composition more than one, first plus
Enter it is a kind of it is evenly dispersed at uniform solution after, then plus it is another, and so on) after, add the liquid moisturizing that step 2) obtains
Lubrication solution stirs 30min, take it is a small amount of test average osmotic pressure, the sodium chloride solution obtained by formula with step 2) or life
Reason salt water adjusts infiltration and is depressed into 295-305mOsmol/kg, pH are as follows: 6.5-7.5 obtains solution A；
4) solution A that step 3) obtains is swollen (> 12h) overnight at room temperature and obtains solution B by, successively 0.8 μm excessively,
0.5 μm, 0.3 μm of filter membrane filters pressing；
5) the filtered liquid of step 4) is placed in 121 DEG C of steam sterilizing 30min in steam sterilization pan by, after steam sterilizing
Stirring, obtains clear homogeneous viscous liquid, sufficient standing to bubble-free, arrives this hair in the filling container to after sterilizing
The composition of bright protection cornea；The viscosity for testing composition is 350mPas-500mPas, if composition viscosity is not in the model
In enclosing, then need to prepare again.
Below in conjunction with specific embodiment, the content of the present invention will be explained in more detail, and the present invention is further elaborated, but
These embodiments limit the invention absolutely not.
Method therefor is conventional method unless otherwise instructed in following embodiments.
The composition of embodiment 1-10, preparation protection cornea
The composition of 1-10 of embodiment of the present invention protection cornea and the formula of comparative example are as shown in table 1-2.Comparative example 1 be by
According to the product that the method in CN102225220A is prepared, comparative example 2 is to be prepared according to the method in TWI290050B
Product, comparative example 3 and 4 is the product being prepared according to the method in CN 104083396A, and comparative example 5 and 6 is according to this
The product that the formula and method of invention are prepared is only solid moisturizing Lubrication Composition not in numberical range of the invention.
1 embodiment 1-5 of table protects the composition of cornea and the formula (composition of every 1000g protection cornea of comparative example 1-3
The quality of middle each component)
2 embodiment 6-10 of table protects the formula (combination of every 1000g protection cornea of the composition and comparative example 4-6 of cornea
The grams of each component in object)
Test one, particular product performance parameters detection
To the composition of protection cornea, the product of comparative example 1-6 and listing similar product of embodiment 1-10 preparation
The performance parameter of CORNEA PROTECT is detected, and the results are shown in Table 3 and table 4.Commercialized product CORNEA PROTECT, purchased from north
Capital and Bang Site development in science and technology Co., Ltd, the product are by hydroxypropyl methyl cellulose (HPMC), sodium chloride, potassium chloride, chlorine
Change calcium, lactic acid and water for injection composition.
The performance parameter of the composition of the protection cornea of 3 embodiment 1-10 of table
The product of 4 comparative example 1-6 of table and the performance parameter of CORNEA PROTECT
It is with reference to " GBT16886.10-2005 BiologicalEvaluationofMedicalDevice " the 10th that eye injury in table 3 and table 4, which is scored,
Part: stimulation evaluate with the B.3 eye irritant test defined in the Appendix B in delayed allergy test.In detail
Thin score system is shown in Table 5.
5 eye injury score system of table
The testing result of performance parameter in contrast table 3 and 4, it can be seen that compared to the composition of embodiment 1-10, comparative example
The product and commercialized product CORNEA PROTECT viscosity of 1-6 is not that too higher position is that too low, endotoxin content and transmitance are not done
Method meets clinical needs simultaneously, and particle number is also excessively high, and it is stringent in formula composition and content to illustrate that composition of the invention passes through
Assemble and screen, the strict control of preparation process just makes that all indicators are better than comparative examples and commercialized product.
CORNEA PROTECT is unique a product for being exclusively used in corneal protection in art on domestic market.CORNEA
The difference of PROTECT and the present composition is the product without liquid moisturizing Lubrication Composition.From the data in the table, this hair
Bright composition adheres to because of the moisturizing greasy property, surface tension, anterior corneal surface that have it containing liquid moisturizing Lubrication Composition
The performances such as power are more suitable for the protection of anterior corneal surface, and its dispersibility and transparency are also superior to un-added product.
In addition the present composition is because containing liquid moisturizing Lubrication Composition and stringent preparation process, so that the present invention combines
Object is better than existing similar product in transmitance and particle index.In this test, it is more than just that commercialized product group, which observed,
Normal discharge of eye, it may be possible to because caused by particle is more.To sum up compare, composition of the invention is more applicable for clinical hand
The moisturizing lubrication of corneal epithelium is maintained in art room ophthalmologic operation and eye examination, to play the role of protecting cornea.
Test two, corneal protection test
In order to verify the present invention protection cornea composition use validity, choose embodiment 1-10, comparative example 1-6 and
Commercialized product CORNEA PROTECT carries out following corneal protection test, and wherein comparative example and commercialized product are implemented as the present invention
The control of example.Specific test method is as follows:
Healthy adult regular grade New Zealand White Rabbit is selected, male and female are unlimited, weight 2.5-3.0Kg.Raising temperature: 20-26 DEG C；
Relative humidity: 40-70%；Illumination: 15-20Lx；Feed complete granular rabbit feed, free water.
With 2wt% Nembutal sodium solution through ear vein injecting anesthetic, lateral position is fixed on operating table experimental animal, is protected
Hold anterior corneal surface level.Embodiment group (using the composition of embodiment 1-10), comparative example group (are used into comparative example 1-6 respectively
Composition), negative control group (physiological saline), positive controls (commercialized product CORNEA PROTECT) blank group (do not make
Use any substance) sample as 3 drop of corneal protection agent drop on animal corneal, and make it that cornea be completely covered.Under microscope
Sample is observed to the coverage condition of anterior corneal surface.Corneal protection agent liquid level thinks covering failure when rupturing.Record is used from drop
Time when corneal protection agent to its liquid level ruptures, the residence time as corneal protection agent.Drop corneal protection is observed simultaneously
After agent within 2 seconds liquid level reflective situation, the smoothness of corneal protection agent liquid level is evaluated with this, using three-level staging, 0
Grade be it is smooth, 1 for part smoothly, 2 be it is unsmooth.The time that sample is dispersed to smooth liquid level in anterior corneal surface is investigated in test,
Disperse more fast more will not make troubles to clinical manipulation.By taking the product of the composition of embodiment 1-6 and comparative example 1-5 as an example, examination
Test that the results are shown in Table 6, other embodiments and the result of embodiment 1-6 are no different.
The corneal protection of each experimental group corneal protection agent of table 6 acts on
| Experimental group | Residence time | Smoothness | Jitter time |
| Blank group | - | - | - |
| Negative control group | 20” | 0 | 1” |
| Positive controls | 16’01”08 | 0 | 10” |
| Embodiment 1 | 15’28”13 | 0 | 3” |
| Embodiment 2 | 14’06”19 | 0 | 2” |
| Embodiment 3 | 15’06”44 | 0 | 2” |
| Embodiment 4 | 15’09”04 | 0 | 3” |
| Embodiment 5 | 17’06”18 | 0 | 4” |
| Embodiment 6 | 10’36”06 | 0 | 3” |
| Comparative example 1 | 20’17”56 | 2 | 51” |
| Comparative example 2 | 23’03”19 | 2 | 55” |
| Comparative example 3 | 28’48”56 | 2 | 48” |
| Comparative example 4 | 18’39”56 | 1 | 37” |
| Comparative example 5 | 31’29”56 | 2 | 59” |
Result in table 6 can be seen that physiological saline and can scatter rapidly in anterior corneal surface, but the residence time is very short
Temporarily, longer as the comparative example 1 of ophthalmically acceptable viscoelastic agent and 2 residence time of comparative example, but rate of dispersion is slower, and observes in experiment
It is same one drop sample covering cornea area it is smaller, need it is subsequent be added dropwise again, again be added dropwise when two drop samples be formed by liquid level it
Between have tomography, also have bubble appearance, cannot sufficiently cover cornea and play a protective role.Sample provided by the present invention, greatly
Can form the smooth liquid level to get a clear view in all 5 seconds, disperse it is very rapid, and the residence time at 10-20 minutes, Neng Gouman
The requirement of sufficient examination of eyes and ophthalmologic operation.As it can be seen that composition of the invention can be taken into account in dispersibility and residence time,
Therefore it is better than existing product.Composition of the invention is the preferential selection of clinical manipulation after overall merit.
The present composition is by quickly forming one layer of clear protective layer in visual area in exposure anterior corneal surface, and it is in cornea table
The residence time in face is longer, will be free from bubble or forms tomography.In clinical operation and eye examination, the application of this composition
So that clinical doctor's operation is more convenient, do not need that physiological saline is frequently added dropwise again, does not need to wait in the consuming time viscous yet
Bullet agent class articles are sprawled in anterior corneal surface, because visual area is more clear so that performing the operation more smooth in operation and checking process；It is another
Aspect, this composition is low in cost, and preparation is simple, can be received by vast sufferer, along with its moisturizing lubrication thinks that energy is good, tool
There is performance identical with natural tear, keeps user more comfortable；Because indices control is stringent in preparation, this composition is used
Avoid the appearance of the complication of the swelling of user's eye and tissue inflammation.
The above is only a preferred embodiment of the present invention, it is noted that for the common skill of the art
For art personnel, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications
Also the contents of the present invention be should be regarded as.
Claims (22)
1. a kind of composition for protecting cornea, main component is solid moisturizing Lubrication Composition, liquid moisturizing Lubrication Composition, infiltration
Press modifying ingredients and water；Wherein, the content of each main component are as follows: the solid moisturizing of the 0.05%-10% based on mass percentage profit
Sliding ingredient, 10%-55% liquid moisturizing Lubrication Composition, the water of 0.8%-1.4% osmotic pressure modifying ingredients and surplus；
The solid moisturizing Lubrication Composition is hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, carragheen
With the combination of one or more of carbomer；
The liquid moisturizing Lubrication Composition is a kind of or several in glycerine, polyethylene glycol-400, polyethylene glycol -300 and propylene glycol
The combination of kind；
The osmotic pressure modifying ingredients is the substance for making the composition osmotic pressure 295-305mOsmol/kg.
2. the composition of protection cornea according to claim 1, it is characterised in that: the liquid moisturizing Lubrication Composition quality
Percentage composition is 10%-45%.
3. the composition of protection cornea according to claim 1, it is characterised in that: the liquid moisturizing Lubrication Composition quality
Percentage composition is 10%-40%.
4. the composition of protection cornea according to claim 1, it is characterised in that: the liquid moisturizing Lubrication Composition quality
Percentage composition is 10%-25%.
5. the composition of protection cornea according to claim 1, it is characterised in that: the solid moisturizing Lubrication Composition quality
Percentage composition is 0.1%-5%.
6. the composition of protection cornea according to claim 1, it is characterised in that: the solid moisturizing Lubrication Composition quality
Percentage composition is 1%-4%.
7. the composition of protection cornea according to claim 1, it is characterised in that: the solid moisturizing Lubrication Composition quality
Percentage composition is 1%-3%.
8. the composition of protection cornea according to claim 1, it is characterised in that: the solid moisturizing Lubrication Composition quality
Percentage composition is 1%-2%.
9. the composition of protection cornea according to claim 1, it is characterised in that: the osmotic pressure modifying ingredients quality hundred
Dividing content is 0.9%-1.4%.
10. the composition of protection cornea according to claim 1, it is characterised in that: the osmotic pressure modifying ingredients quality
Percentage composition is 0.83%-1%.
11. the composition of protection cornea according to claim 1, it is characterised in that: the osmotic pressure modifying ingredients quality
Percentage composition is 1%-1.4%.
12. the composition of protection cornea according to claim 1, it is characterised in that: the osmotic pressure modifying ingredients quality
Percentage composition is 1%-1.2%.
13. the composition of protection cornea according to claim 1, it is characterised in that: the hydroxypropyl methyl cellulose choosing
Nominal viscosity is one or more of 6,15,50,100,250,750,1500,4000,10000 and 15000mPas；
The sodium carboxymethylcellulose selects high viscosity, medium viscosity or low viscosity, high viscosity, that is, sodium carboxymethylcellulose concentration to exist
Range of viscosities when 1wt% is 1000-4500mPas, viscosity model when medium viscosity, that is, sodium carboxymethylcellulose concentration 2wt%
It encloses for 300-3100mPas, the range of viscosities of concentration is 25-100mPas when low viscosity, that is, sodium carboxymethylcellulose 2wt%；
The average molecular weight that the hydroxypropyl cellulose is selected is 80000,95000,140000,370000,850000 and
One or more of 1150000；
The carragheen selects medical rank.
14. the composition of protection cornea according to claim 1, it is characterised in that: the carbomer selects carbomer
910, carbomer 934, Acritamer 940, Carbopol 941.
15. the composition of protection cornea according to claim 1, it is characterised in that: the osmotic pressure modifying ingredients is selected from
The one or more combination of sodium chloride, potassium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, zinc gluconate, lactic acid.
16. the composition of protection cornea according to claim 15, it is characterised in that: the osmotic pressure modifying ingredients is pressed
Final mass percentage composition in the composition contains following substance: sodium chloride (NaCl) 0.505%-0.710%, chlorination
Potassium (KCl) 0%-0.021%, sodium dihydrogen phosphate (NaH2PO4) 0.052%-0.142%, potassium dihydrogen phosphate (KH2PO4)0.027-
0.166%, zinc gluconate 0-0.5% and lactic acid 0-0.01%.
17. a kind of method for the composition for preparing any one of claim 1-16 protection cornea, which is characterized in that will permeate
Pressure modifying ingredients is dissolved in filtration sterilization after water dissolution, obtains osmotic pressure and adjusts solution；Adsorption treatment liquid moisturizing Lubrication Composition, obtains
To liquid moisturizing lubrication solution；By solid moisturizing Lubrication Composition be slowly added to one by one osmotic pressure adjust solution in and it is evenly dispersed at
Uniform solution adds liquid moisturizing lubrication solution, adjusts infiltration with saturated sodium chloride solution or physiological saline and is depressed into 295-
305mOsmol/kg, swelling are stayed overnight, filtration sterilization.
18. according to the method for claim 17, which comprises the following steps:
1) weighs that osmotic pressure modifying ingredients is soluble in water to be configured to salting liquid, after crossing 0.22 μm of filter membrane, 121 DEG C of steam sterilizings
30min obtains osmotic pressure and adjusts solution；
2) weighs at least one of liquid moisturizing Lubrication Composition, respectively with active carbon is removed after activated carbon adsorption, is mixed to get
Liquid moisturizing lubrication solution；It is another to prepare the sodium chloride solution that sodium chloride mass percentage is 26.5wt%, 121 DEG C of steam sterilizings
30min；
3) solid moisturizing Lubrication Composition is slowly added in osmotic pressure adjusting solution by one by one under 65 ± 5 DEG C, stirring condition, to
Solid moisturizing Lubrication Composition is evenly spread out to form uniform solution after, add the liquid moisturizing lubrication solution that step 2) obtains and stir
30min is mixed, infiltration is adjusted with the sodium chloride solution or physiological saline of 26.5wt% and is depressed into 295-305mOsmol/kg, obtain solution
A；
4) solution A that step 3) obtains is swollen > 12h at room temperature and obtains solution B by, successively crosses 0.8 μm, 0.5 μm, 0.3 μm
Filter membrane filters pressing；
5) liquid after step 4) filters pressing is placed in 121 DEG C of steam sterilizing 30min in steam sterilization pan by, is stirred after steam sterilizing,
Obtain clear homogeneous viscous liquid；Sufficient standing arrives the composition of the protection cornea to bubble-free.
19. according to the method for claim 18, which is characterized in that osmotic pressure modifying ingredients is in the composition in step 1)
In final concentration of 0.505wt%-0.710wt% sodium chloride (NaCl), the potassium chloride (KCl) of 0wt%-0.021wt%,
Sodium dihydrogen phosphate (the NaH of 0.052wt%-0.142wt%2PO4), the potassium dihydrogen phosphate of 0.027wt%-0.166wt%
(KH2PO4), the zinc gluconate of 0wt%-0.5wt% and the lactic acid of 0wt%-0.01wt%.
20. according to the method for claim 18, which is characterized in that if solid moisturizing Lubrication Composition more than one in step 3)
Kind, then be first added it is a kind of it is evenly dispersed at uniform solution after, then plus it is another, and so on.
21. a kind of composition for the protection cornea being prepared by claim 17-20 the method, which is characterized in that viscosity
For 350mPas-500mPas, endotoxin content < 0.5EU/mL, the particle number that 10 μm of transmitance > 99%, > is less than
600, > 25 μm of particle number is less than 15.
22. application of the composition of any protection cornea of claim 1-16 in the drug that preparation avoids bitot's patches,
The drug is eye drops, irrigation or liniment.
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| CN107158452B (en) * | 2017-05-05 | 2020-05-01 | 赛克赛斯生物科技股份有限公司 | Bone wound hemostatic composition and preparation method and application thereof |
| CN112076152A (en) * | 2020-09-23 | 2020-12-15 | 江苏地韵医疗科技有限公司 | Ophthalmic composition, preparation method and application thereof |
Citations (3)
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|---|---|---|---|---|
| GB2204238A (en) * | 1987-05-04 | 1988-11-09 | Mdr Group Inc | Viscoelastic fluid for opthalmic surgery |
| CA2125060C (en) * | 1993-07-02 | 1999-03-30 | Henry P. Dabrowski | Ophthalmic solution for artificial tears |
| CN103547257A (en) * | 2011-03-03 | 2014-01-29 | 克罗马药品有限责任公司 | Use of a viscoelastic fluid for producing a medicinal product for surgically treating the eye |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006004577A2 (en) * | 2004-03-12 | 2006-01-12 | Melbj Holdings, Llc | Lubricant for the ocular surface |
-
2016
- 2016-03-28 CN CN201610184155.4A patent/CN105749360B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2204238A (en) * | 1987-05-04 | 1988-11-09 | Mdr Group Inc | Viscoelastic fluid for opthalmic surgery |
| CA2125060C (en) * | 1993-07-02 | 1999-03-30 | Henry P. Dabrowski | Ophthalmic solution for artificial tears |
| CN103547257A (en) * | 2011-03-03 | 2014-01-29 | 克罗马药品有限责任公司 | Use of a viscoelastic fluid for producing a medicinal product for surgically treating the eye |
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| Title |
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| 粘弹性物质及其在眼科的应用;辛容等;《中国实用眼科杂志》;19971231;第15卷(第10期);第578-587页 |
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