CN104083396B - Anterior corneal surface protective agent and its preparation method and application - Google Patents
Anterior corneal surface protective agent and its preparation method and application Download PDFInfo
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Abstract
The invention belongs to field of medical article technology, and in particular to a kind of anterior corneal surface protective agent, further relate to the protectant preparation method of the anterior corneal surface, and this product application.The anterior corneal surface protective agent of the present invention includes following components：Molecular weight is 100,000 D to 2,000,000 D Sodium Hyaluronate, concentration range 5mg/ml to 200mg/ml；Or the chondroitin sulfate that molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 200mg/ml；Or the chitosan that molecular weight is 5KD to 2,000,000 D, concentration range 5mg/ml to 200mg/ml.With traditional preservation liquid phase ratio for being only applied to preserve in vitro cornea tissue; using the preparation-obtained anterior corneal surface protective agent of method of the present invention; it can be applied in clinical operation; anterior corneal surface is applied in surgical procedure; the moistening and translucency of cornea can be kept within a period of time; the frequency of operation midpoint water is considerably reduced, the operation progress of acceleration improves patient comfort.
Description
Technical field
The invention belongs to field of medical article technology, and in particular to a kind of anterior corneal surface protective agent, further relate to the cornea table
The protectant preparation method in face, and this product application.
Background technology
Cornea keeps moistening and good translucency to be the necessary conditions that operation is carried out in ophthalmologic operation, in existing operation
Need frequently to realize above-mentioned purpose in anterior corneal surface water, and Normal Saline or buffer solution are maintained at anterior corneal surface
Uniform fold be difficult to exceed half a minute, the point sailor in surgical procedure continues cumbersome, have impact on the progress of operation, adds simultaneously
The discomfort of patient.The corneal protection agent of this research and design is applied to anterior corneal surface in surgical procedure, can be within a period of time（5-
10 minutes）The moistening and translucency of cornea are kept, the frequency for considerably reducing operation midpoint water, the operation of acceleration can be made
Progress, improves patient comfort.
CN1262866A discloses a kind of cornea activity preservative fluid, contains in the preservation liquid：MEM cell culture mediums 4.5-
4.9g, chondroitin sulfate 12-13g, D-40 4.8-5.2g, dexamethasone 12-14mg, antibiotic 48-52mg and
HEPES4.5-5.0g, the rest is deionized water, and they are well mixed successively, adjust pH value to reach 7.2-7.4, through packing, sealing
Into finished product, 4 DEG C of preservations.
Above-mentioned preservation liquid can make the holding time of cornea activity up to more than 2 weeks, and endothelial cell activity is stable during storage,
Change is small, and the Optisol that can be produced with u s company matches, and by clinic application, preservation of cornea is reused after more than 7 days, art
Piece endothelial cell number is planted within 1-4 weeks afterwards more than 1500/mm2, and required raw material is easy to get, cheap, good economy performance, is adapted to
Domestic Mid-term preservation method.
CN1270605C discloses a kind of cornea middle term preserving fluid, contains in the preservation liquid：RPMI1640 nutrient solutions 4.2-
6.2g, chondroitin sulfate 15-35mg, hyaluronic acid 5-25 mg, HEPES buffer solution 3.76-5.76 g, dexamethasone 5-50
Mg, it is characterised in that：Low molecular weight seaweed polysaccharide 10-30 mg also containing 25000-100000Da, TOB or mould through the ages
Plain 10-150 mg, the wherein specification of TOB are the units of 25-50 ten thousand；The preservation liquid is light red orange, transparent slight viscous fluid
Body, its pH value is 7.0-7.6, osmotic pressure 300-400m0sm/KgH2O, in 2-6 DEG C of preservation.The advantage of the above method is to make
The holding time of cornea activity, endothelial cell activity was stable during storage up to more than 2 weeks, changed small, and in epithelial cell
It is better than the Optisol of u s company's production on holding time, enzyme histochemistry checks extension of the display with the holding time, above-mentioned
The liquid that preserves maintain higher endothelial cell bag function than Optisol.By clinic application, preservation of cornea makes again after more than 7 days
With plant piece endothelial cell number is more than 2000/mm within postoperative 1-4 weeks2.Raw material needed for the cornea middle term preserving fluid of foregoing invention is easy
, cheap, good economy performance is adapted to country's Mid-term preservation method.
CN101524063B discloses a kind of cornea middle term preserving fluid, and the preservation liquid is made into using distilled water as solution
Contain DMEM culture medium 0.5-1.5g, hydroxypropyl methyl cellulose 1-10 g, 2 mercapto ethanol in 1000ml solution, the solution
0.1-10ml, the dextran 10-20g of molecular weight 40000, nonessential amino acid 1-3mol, HEPES buffer solution 10-32mol,
Dexamethasone 0.01-0.05mmol, gentamicin 50-70mg, the pH value of the preservation liquid is 7.2-8.0, and osmotic pressure is 350-
400mmol/L.Above-mentioned patent can reduce cell metabolization rate, and cytotoxic evil is acted on, colloid osmotic pressure can be improved,
And it is cheap, not only with good preservation of cornea quality, and also excellent cost performance, it is that one kind is widely used in state
The inside and outside suitable cornea middle term preserving fluid of eye bank.
But the purposes of above-mentioned preservation liquid is only limitted to preserve in vitro cornea tissue, not yet uses in clinical operation,
Clinical operation whether is can apply to for above-mentioned preservation liquid, several above-mentioned technologies are not disclosed, it is therefore desirable to which design is a kind of
The anterior corneal surface protective agent that can apply in clinical operation, and the anterior corneal surface protective agent is kept cornea within a period of time
Moistening and the transparency, reduction operation midpoint water frequency, the operation progress of acceleration, improve patient comfort.
The content of the invention
In order to solve above-mentioned technical problem, the invention provides a kind of anterior corneal surface protective agent, it is mainly used in art
The protection on corneal surface, anterior corneal surface protective agent of the invention can keep anterior corneal surface to moisten and keep within a certain period of time
The good transparency of cornea, to provide good surgical field of view.
Present invention also offers the protectant preparation method of above-mentioned anterior corneal surface.
The anterior corneal surface protective agent of the present invention includes following components：
Molecular weight is 100,000 D to 2,000,000 D Sodium Hyaluronate, concentration range 5mg/ml to 200mg/ml；
Or the chondroitin sulfate that molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 200mg/ml；
Or the chitosan that molecular weight is 5KD to 2,000,000 D, concentration range 5mg/ml to 200mg/ml.
It is preferred that, above-mentioned anterior corneal surface protective agent includes following components：
Molecular weight is 200,000 D to 1,500,000 D Sodium Hyaluronate, concentration range 5mg/ml to 100mg/ml；
Or the chondroitin sulfate that molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 50mg/ml；
Or the chitosan that molecular weight is 10,000 D to 1,000,000 D, concentration range 20mg/ml to 200mg/ml.
The protectant preparation method of above-mentioned anterior corneal surface, including following steps：
0.045g NaH is weighed respectively2PO4·H2O, 0.2g Na2HPO4And 0.44g NaCl, it is dissolved in 100mL notes
Cushioning liquid is configured in jetting, treats that above-mentioned raw material is completely dissolved, using 0.22 micron membrane filter filtration sterilization；
The Sodium Hyaluronate for weighing 0.5g to 20g is dissolved in 100ml buffer solution, obtains corneal protection agent；
Or 0.5g to 20g chondroitin sulfate is dissolved in 100ml buffer solution, corneal protection agent is obtained；
Or 0.5g to 20g chitosan, it is dissolved in 100ml buffer solution, obtains corneal protection agent；
The molecular weight of above-mentioned Sodium Hyaluronate is 100,000 D to 2,000,000 D Sodium Hyaluronate, and concentration range 5mg/ml is extremely
200mg/ml；
Above-mentioned chondroitin sulfate molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 200mg/ml；
Above-mentioned chitosan molecule amount is 10,000 D to 2,000,000 D, concentration range 5mg/ml to 200mg/ml.
It is preferred that, the protectant preparation method of above-mentioned anterior corneal surface, including following steps：
0.045g NaH is weighed respectively2PO4·H2O, 0.2g Na2HPO4And 0.44g NaCl, it is dissolved in 100mL notes
Cushioning liquid is configured in jetting, treats that above-mentioned raw material is completely dissolved, using 0.22 micron membrane filter filtration sterilization；
The Sodium Hyaluronate for weighing 0.5g to 20g is dissolved in 100ml buffer solution, obtains corneal protection agent；
Or 0.5g to 20g chondroitin sulfate is dissolved in 100ml buffer solution, corneal protection agent is obtained；
Or 0.5g to 20g chitosan, it is dissolved in 100ml buffer solution, obtains corneal protection agent；
The molecular weight of Sodium Hyaluronate is 200,000 D to 1,500,000 D, concentration range 5mg/ml to 100mg/ml；
Chondroitin sulfate molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 50mg/ml；
Chitosan molecule amount is 10,000 D to 1,000,000 D, concentration range 20mg/ml to 200mg/ml.
It is preferred that, the protectant preparation method of above-mentioned anterior corneal surface, including following steps：
0.045g NaH is weighed respectively2PO4·H2O, 0.2g Na2HPO4And 0.44g NaCl, it is dissolved in 100mL notes
Cushioning liquid A is configured in jetting, the TOB pulvis added in cushioning liquid to final concentration 2-5mg/ml, and/or ground
Meter Song Yuan liquid is filled in final concentration 0.5-1mg/ml, is stirred, is treated that above-mentioned raw material is completely dissolved, obtain cushioning liquid B, to buffering
Solution B uses 0.22 micron membrane filter filtration sterilization；
The Sodium Hyaluronate for weighing 0.5g to 20g is dissolved in 100ml buffer solution, obtains corneal protection agent；
Or 0.5g to 20g chondroitin sulfate is dissolved in 100ml buffer solution, corneal protection agent is obtained；
Or 0.5g to 20g chitosan, it is dissolved in 100ml buffer solution, obtains corneal protection agent；
The molecular weight of Sodium Hyaluronate is 100,000 D to 2,000,000 D, concentration range 5mg/ml to 200mg/ml；
Chondroitin sulfate molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 200mg/ml；
Chitosan molecule amount is 10,000 D to 2,000,000 D, concentration range 5mg/ml to 200mg/ml.
TOB and dexamethasone had clinical ophthalmology applicating history for many years, can effective prevention of postoperative
Infection and aseptic inflammation.The existing clinical ophthalmology medicine for having an analogous components includes Tobrex eye water, and allusion quotation must different eye water etc..
The viscosity of this product viscosity more general clinical practice eye water is high, and the time of contact in art with cornea and eye its hetero-organization is more general
The eye water retention time of logical clinical practice is long, it is contemplated that have preferable postoperative antibacterial anti-infection effect.
It is furthermore preferred that the protectant preparation method of anterior corneal surface, including following steps：
0.045g NaH is weighed respectively2PO4·H2O, 0.2g Na2HPO4And 0.44g NaCl, it is dissolved in 100mL notes
Cushioning liquid A is configured in jetting, TOB pulvis is added in cushioning liquid to final concentration 2-5mg/ml, and/or ground plug
Meter Song Yuan liquid stirs to final concentration 0.5-1mg/ml, treats that above-mentioned raw material is completely dissolved, obtains cushioning liquid B, molten to buffering
Liquid B uses 0.22 micron membrane filter filtration sterilization；
The Sodium Hyaluronate for weighing 0.5g to 10g is dissolved in 100ml buffer solution, obtains corneal protection agent；
Or 0.5g to 5g chondroitin sulfate is dissolved in 100ml buffer solution, corneal protection agent is obtained；
Or 2g to 20g chitosan, it is dissolved in 100ml buffer solution, obtains corneal protection agent；
The molecular weight of Sodium Hyaluronate is 200,000 D to 1,500,000 D, concentration range 5mg/ml to 100mg/ml；
Chondroitin sulfate molecular weight is 5KD to 100,000 D, concentration range 5mg/ml to 50mg/ml；
Chitosan molecule amount is 10,000 D to 1,000,000 D, concentration range 20mg/ml to 200mg/ml.
It is eye drops to adopt its formulation of anterior corneal surface protective agent prepared with the aforedescribed process.
Application of the anterior corneal surface protective agent of the present invention in ophthalmologic operation, ophthalmologic operation includes the hand of all exposed corneas
Art, specifically includes cataract extraction, and intraocular lens implantation, operation for glaucoma, strabotomy, Vitrectomy consolidates
Pad pressure operation outside film, corneal cracking suture, scleral rupture suture, above-mentioned application also protection scope of the present invention it
It is interior.
The beneficial effects of the present invention are, and traditional preservation liquid phase ratio for being only applied to preserve in vitro cornea tissue,
It using the preparation-obtained anterior corneal surface protective agent of method of the present invention, can be applied in clinical operation, applied in surgical procedure
Smear in anterior corneal surface, the moistening and the transparency of cornea can be kept within a period of time, operation midpoint water is considerably reduced
Frequency, the operation progress of acceleration, improves postoperative patient comfort level.
Brief description of the drawings
Fig. 1 is that anterior corneal surface fluorescent staining is shown, it is in diffused point-like that corneal epithelium after physiological saline eye droppings is used in art
It is epithelium deletion sites at missing, arrow；
Fig. 2 is that anterior corneal surface fluorescent staining is shown, uses cornea Epithelial morphology after corneal protection agent eye droppings intact in art.
Fig. 3 lacks the statistical analysis carried out to be postoperative by anterior corneal surface fluorescent staining corneal epithelial, and display cornea is protected
The epithelium missing for protecting agent group is substantially less than physiological saline group (P<0.05)；
Fig. 4 analyzes for the pain index of postoperative patient, shows that patient's postoperative pain degree of corneal protection agent group is significantly low
In patient pain's index (P of physiological saline group<0.05).
Embodiment
The present invention is further described with reference to specific embodiment, so that those skilled in the art knows more about
The present invention, but and it is not so limited the present invention.
Embodiment 1
In cataract extraction+intraocular lens implantation, the Sodium Hyaluronate that molecular weight is 500,000, concentration 9mg/ml are used.
Preparation method is：0.045g NaH is weighed respectively2PO4·H2O, 0.2g Na2HPO4And 0.44g NaCl,
It is dissolved in 100mL injection waters and is configured to cushioning liquid A, TOB pulvis is added in cushioning liquid to final concentration 3mg/ml,
And dexamethasone stoste stirs to final concentration 0.6mg/ml, treat that above-mentioned raw material is completely dissolved, obtain cushioning liquid B, it is right
Cushioning liquid B uses 0.22 micron membrane filter filtration sterilization；The Sodium Hyaluronate that 0.9g molecular weight is 500,000 is weighed to be dissolved in
In 100ml buffer solution, corneal protection agent is obtained；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, refractive status is good, it is ensured that clear, the good refractive status that this product is kept and flat of surgical field of view
Surface is held time about at 10 minutes or so, operation can just be smoothly completed 1 time by being used only in art, it is to avoid traditional operation intermediate frequency
Numerous drips to maintain good surgical field of view in anterior corneal surface.Corneal epithelium is evaluated in postoperative progress anterior corneal surface fluorescent staining
Protection situation, display is lacked using the corneal epithelium of physiological saline patient in diffused point-like（Accompanying drawing 1）, and use this product
Corneal epithelium form it is intact, have no missing（Accompanying drawing 2）.Clinical investigation, wherein physiology salt are carried out to 22 patient's postoperative effects
Water group 12, corneal protection agent group 10 examines two experimental group statistical data differences of contrast, P using T<0.05 is to have aobvious
Write difference.Data display, postoperative 1st, 2,3 day physiological saline group corneal epithelium point-like lacks quantity（66±13）It is significantly higher than angle
Film protective agent group corneal epithelium point-like lacks quantity（5±1）（Accompanying drawing 3）（P<0.05）.Postoperative progress eye's pain sensation investigation
Questionnaire（0：Analgesia；1：The slight pain sensation, holds time<1 day；2：The moderate pain sensation, holds time<1 day；3：The moderate pain sensation, is maintained
Time>1 day；4：The severe pain sensation, it is impossible to or be difficult to fall asleep）, questionnaire shows physiological saline group patient pain sensation parameter in postoperative 3 days
（2.1±0.6）It is significantly higher than corneal protection agent group patient's pain sensation parameter（0.3±0.06）（Accompanying drawing 4）（P<0.05）.
Embodiment 2
Buffer solution is made using the method in embodiment 1, molecular weight is dissolved in for 20,000 chondroitin sulfate 1.5g
In 100ml buffer solution, corneal protection agent is obtained, in cataract extraction+intraocular lens implantation；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, the good refractive status and flat surface kept is held time about at 10 minutes or so, is used 1 time in art.
16 patient's postoperative effects are carried out with clinical investigation, wherein physiological saline group 10, corneal protection agent group 6 uses T inspections pair
Than two experimental group statistical data differences, P<0.05 is there were significant differences.Data display, postoperative 1st, 2,3 day physiological saline
Group corneal epithelium point-like missing quantity（59±9）It is significantly higher than corneal protection agent group corneal epithelium point-like missing quantity（4±1）
（Accompanying drawing 3）（P<0.05）.Physiological saline group patient pain sensation parameter in postoperative 3 days（2.2±1.1）It is significantly higher than corneal protection agent group
Patient's pain sensation parameter（0.3±0.1）（Accompanying drawing 4）（P<0.05）.
Embodiment 3
Buffer solution is made using the method in embodiment 1, molecular weight is dissolved in 100ml's for 700,000 chitosan 1.0g
In buffer solution, corneal protection agent is obtained, in cataract extraction+intraocular lens implantation；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, the good refractive status and flat surface kept is held time about at 10 minutes or so, is used 1 time in art.
13 patient's postoperative effects are carried out with clinical investigation, wherein physiological saline group 5, corneal protection agent group 8 uses T inspections pair
Than two experimental group statistical data differences, P<0.05 is there were significant differences.Data display, postoperative 1st, 2,3 day physiological saline
Group corneal epithelium point-like missing quantity（71±16）It is significantly higher than corneal protection agent group corneal epithelium point-like missing quantity（5±1）
（Accompanying drawing 3）（P<0.05）.Physiological saline group patient's pain sensation parameter (2.6 ± 0.9) is significantly higher than corneal protection agent group in postoperative 3 days
Patient's pain sensation parameter（0.3±0.2）（Accompanying drawing 4）（P<0.05）.
Embodiment 4
Using the corneal protection agent in embodiment 1, for operation for glaucoma（Trabecular resection+iris week cuts art）In；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, refractive status is good, it is ensured that clear, the good refractive status that this product is kept and flat of surgical field of view
Surface is held time about at 10 minutes or so, and this operating time 20 minutes or so is used 2 times in art.To the postoperative effect of 19 patients
Fruit carries out clinical investigation, wherein physiological saline group 7, and corneal protection agent group 12 examines two experimental group data of contrast using T
Significant difference, P<0.05 is there were significant differences.Data display, postoperative 1st, 2,3 day physiological saline group corneal epithelium point-like lacks
Lose quantity（126±21）It is significantly higher than corneal protection agent group corneal epithelium point-like missing quantity（9±2）（Fig. 3）（P<0.05）.Art
Physiological saline group patient's pain sensation parameter (3.1 ± 1.1) is significantly higher than corneal protection agent group patient's pain sensation parameter in 3 days afterwards（0.3±
0.05）（Accompanying drawing 4）（P<0.05）.
Embodiment 5
Using the corneal protection agent in embodiment 1, for repositio retinae（Vitreum cutting+repositio retinae）
In；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, refractive status is good, it is ensured that clear, the good refractive status that this product is kept and flat of surgical field of view
Surface is held time about at 10 minutes or so, and this operating time 60 minutes or so is used 3 times in art.To the postoperative effect of 16 patients
Fruit carries out clinical investigation, wherein physiological saline group 9, and corneal protection agent group 7 examines two experimental group data of contrast using T
Significant difference, P<0.05 is there were significant differences.Data display, postoperative 1st, 2,3 day physiological saline group corneal epithelium point-like lacks
Lose quantity（291±51）It is significantly higher than corneal protection agent group corneal epithelium point-like missing quantity（21±7）（Fig. 3）（P<0.05）.
Physiological saline group patient's pain sensation parameter (3.2 ± 0.3) is significantly higher than corneal protection agent group patient's pain sensation parameter in postoperative 3 days（0.5
±0.06）（Fig. 4）（P<0.05）.
Embodiment 6
Using the corneal protection agent in embodiment 2, for repositio retinae（Vitreum cutting+repositio retinae）
In；
0.2ml product of the invention is dripped in anterior corneal surface using syringe in art, the flat liquid in surface is formed after 2 seconds
Body interface, refractive status is good, it is ensured that clear, the good refractive status that this product is kept and flat of surgical field of view
Surface is held time about at 10 minutes or so, and this operating time 60 minutes or so is used 5 times in art.To the postoperative effect of 16 patients
Fruit carries out clinical investigation, wherein physiological saline group 6, and corneal protection agent group 10 examines two experimental group data of contrast using T
Significant difference, P<0.05 is there were significant differences.Data display, postoperative 1st, 2,3 day physiological saline group corneal epithelium point-like lacks
Lose quantity（336±61）It is significantly higher than corneal protection agent group corneal epithelium point-like missing quantity（26±9）（Fig. 3）（P<0.05）.
The physiological saline group patient pain sensation (3.4 ± 0.6) parameter is significantly higher than corneal protection agent group patient's pain sensation parameter in postoperative 3 days
（0.31±0.09）（Fig. 4）（P<0.05）.
In accompanying drawing 3, corneal protection agent 1,2,3 can be in cataract operation, and operation for glaucoma, reattachment of retina is postoperative significantly
Reduce corneal epithelium missing.（P<0.05）（Corneal protection agent 1：Molecular weight is 500,000 Sodium Hyaluronate, concentration 9mg/ml；Angle
Film protective agent 2：Molecular weight is 20,000 chondroitin sulfate, and concentration is 15mg/ml；Corneal protection agent 3, molecular weight is 700,000 shell
Glycan, concentration is 10mg/ml）.
In accompanying drawing 4, corneal protection agent 1,2,3 can be in cataract operation, and operation for glaucoma, reattachment of retina is postoperative significantly
Mitigate patient's pain sensation.（P<0.05）（Corneal protection agent 1：Molecular weight is 500,000 Sodium Hyaluronate, concentration 9mg/ml；Cornea is protected
Protect agent 2：Molecular weight is 20,000 chondroitin sulfate, and concentration is 15mg/ml；Corneal protection agent 3, molecular weight is 700,000 chitosan,
Concentration is 10mg/ml）.
Claims (2)
1. anterior corneal surface protective agent is used as the application of wetting agent, it is characterised in that
Anterior corneal surface protective agent is obtained by following preparation method：0.045g NaH is weighed respectively2PO4·H2O, 0.2g's
Na2HPO4And 0.44g NaCl, it is dissolved in 100mL injection waters and is configured to cushioning liquid A, is added in cushioning liquid A
TOB pulvis stirs to final concentration 2-5mg/ml, and/or dexamethasone stoste to final concentration 0.5-1mg/ml, treats
Above-mentioned raw material is completely dissolved, and obtains cushioning liquid B, and 0.22 micron membrane filter filtration sterilization is used to cushioning liquid B；
Weigh the Sodium Hyaluronate that 0.9g molecular weight is 500,000 to be dissolved in 100ml cushioning liquid B, obtain corneal protection agent；
Or be dissolved in molecular weight in 100ml cushioning liquid B for 20,000 chondroitin sulfate 1.5g, obtain corneal protection agent；
Molecular weight is dissolved in 100ml cushioning liquid B for 700,000 chitosan 1.0g, corneal protection agent is obtained.
2. the protectant preparation method of anterior corneal surface as claimed in claim 1, it is characterised in that prepared using described method
Obtained its formulation of anterior corneal surface protective agent is eye drops.
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| RU2585956C1 (en) * | 2015-05-12 | 2016-06-10 | Общество с ограниченной ответственностью "Дубна-Биофарм" | Solution - protector of cornea and other surfaces of eye |
| CN105816477A (en) * | 2016-02-29 | 2016-08-03 | 李志伟 | Application of cornea surface protection agent in general anaesthesia operations |
| CN106614519B (en) * | 2016-11-24 | 2019-11-19 | 山东省眼科研究所 | A kind of preparation method of de- cell corneal limbus protection liquid and de- cell corneal limbus |
| CN107812243A (en) * | 2017-09-21 | 2018-03-20 | 李春晖 | A kind of corneal protection viscoelastic liquid |
| CN108371729A (en) * | 2018-05-22 | 2018-08-07 | 上海建华精细生物制品有限公司 | There is the viscoelastic agent for ophthalmic surgery and its preparation method and application of radicals scavenging function |
| CN113876800A (en) * | 2021-11-11 | 2022-01-04 | 天津晶明新技术开发有限公司 | Cornea protective agent and its preparation method and use |
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| CN101461781A (en) * | 2009-01-06 | 2009-06-24 | 河北科技大学 | Gernebcin eye drops without bacteriostatic agent and preparation method thereof |
| CN101951879A (en) * | 2007-11-30 | 2011-01-19 | 阿勒根公司 | Polysaccharide gel formulation |
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Effective date of registration: 20231011 Address after: Room 701, Building 4, A7 District, Hanyu Jingu, Jinan City, Shandong Province, 250102 Patentee after: Three dimensional medical technology Co.,Ltd. Address before: No. 9677 Jingshi Road, High tech Zone, Jinan City, Shandong Province, 250103 Patentee before: Mou Guoying Patentee before: Li Zhiwei |