CN100577187C - Chinese medicine preparation for treating eye fatigue and its preparing process - Google Patents
Chinese medicine preparation for treating eye fatigue and its preparing process Download PDFInfo
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- CN100577187C CN100577187C CN200610046146A CN200610046146A CN100577187C CN 100577187 C CN100577187 C CN 100577187C CN 200610046146 A CN200610046146 A CN 200610046146A CN 200610046146 A CN200610046146 A CN 200610046146A CN 100577187 C CN100577187 C CN 100577187C
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Abstract
The Chinese medicine preparation for treating eye fatigue and myopia is prepared with total dactylicaponos scandens alkaloid, gel matrix for eye medicine and water, and through mixing, pH regulation to 4-9 and further stirring to form homogeneous gel. It has eye slow release and good biocompatibility. Compared with available technology, the present invention has the advantages of being slow released, comfortable, less stimulation and easy to eliminate.
Description
(1) technology neck city:
The present invention relates to a kind of treatment myopia and asthenopic Chinese medicine and preparation method thereof; Be raw material specifically with the Chinese herbal medicine, a kind of adolescent myopia, pseudomyopia and the continuous pure Chinese medicinal preparation of caused eyestrain of vision and diseases such as eye is aching and tired, eye socket pain and preparation method thereof that closely uses of being used for the treatment of that is prepared into.
(2) technical background
Quickening along with the modern cultural rhythm of life, work, study hypertonicity, over-burden for psychological diathesis, the unclean pollution of ecological environment in addition, as influence and self psychentonia of air qualities such as air dust, smog, it is improper that work and rest is coordinated, long-term excess eye-using or eyes can not get taking good care of fully and having a rest, all multifactor eyes pathological changes of bringing out are more and more simultaneously, pathological changes in various degree can cause eye vision and descend, form myopia, amblyopia, asthenopia or diseases such as eye is aching and tired, eye frame pain occur, seriously can make blurred vision, dim eyesight even blind.According to the incomplete statistics of social medicine newspapers and periodicals interrelated data, eye vision decline and rate of myopia account for 40%～60% among the large, medium and small student in the whole nation, its students in middle and primary schools' rate of myopia is 4.9%, just, rate of myopia is 52% among the high school student, and myopia, amblyopia, asthenopia disease sickness rate rise with annual 5% speed.Heredity and developing myopia have become the current serious social problem that influences the teenager vision health.Therefore, seek effective anti-eyestrain's pharmaceutical preparation, pre-myopia prevention is eliminated asthenopia, recovers vision health, and control and prevention ophthalmic disease is problem and the direction that domestic and international ophthalmology academia joint research is inquired into always.
(3) summary of the invention
The object of the present invention is to provide a kind ofly have that prescription is rigorous, compatibility science, treatment cycle weak point, instant effect, evident in efficacy, asthenopic Chinese medicine preparation of treatment and the preparation method consolidating the rate height, be difficult for recurrence, have no side effect.
For achieving the above object, the technical solution used in the present invention is:
The invention provides the asthenopic Chinese medicine preparation of a kind of treatment, it includes the effective constituent Radix dactylicapni (Radix Dactylicapnotis) total alkaloids and ophthalmic preparation substrate.Every 1000ml contains Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 1-10g.
Described ophthalmic preparation substrate is selected from one or more in carbomer (as carbomer 971,941,973,940,934 etc.), cellulose derivative (as methylcellulose, hydroxy methocel, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose etc.), polyvinylpyrrolidone, crospolyvinylpyrrolidone, poly-ethanol, the Polyethylene Glycol etc.
Principal agent Radix dactylicapni (Radix Dactylicapnotis) of the present invention (medical material) is preferably 20～80% (medical material percentage by weights) at the content of treatment in the asthenopic Chinese medicine preparation gel, and more preferably 50%; The content of the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids in the gel of this medicine is preferably 1～10 ‰ (g/ml).
Also can contain osmotic pressure regulator, antiseptic or antibacterial, thickening agents in the asthenopic Chinese medicine preparation gel of treatment of the present invention.Wherein antiseptic or antibacterial are selected from ethyl hydroxybenzoate, methyl hydroxybenzoate, propylparaben, chlorobutanol, thimerosal, mercuric oxycyanide, bromo geramine or geramine etc.Osmotic pressure regulator is selected from sodium chloride or glucose, boric acid, Borax, sodium sulfate, sodium dihydrogen phosphate etc.The content of osmotic pressure regulator is preferably 0.1～1.0wt%, and the content of antiseptic or antibacterial is preferably 0.1～5.0wt%.But thickening agents preferable methyl cellulose, polyvidone, polyvinyl alcohol, vaseline.
A kind of dosage form for the treatment of asthenopic Chinese medicine preparation comprises gel, eye drop, eye micropill, collyrium, ophthalmic ointment, tablet, capsule or granule and corresponding sustained-release preparation.
A kind of preparation method for the treatment of asthenopic Chinese medicine preparation, 1000ml is an example with preparation, mainly is with Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 1-10g and ophthalmic gel base 0.1-20g, an amount of water for injection mixes, stir into gel, adjust pH is to 4-9, adds the injection water and stirs to 1000ml and be prepared into.Can be after the sterilization by setting the specification packing.
The pH regulator agent is a Borax 0.2～2.0%, gel for eye 500ml or 1000ml that sodium hydroxide 0.01～0.1%, triethanolamine 0.1～1.0% are made.
By in the above-mentioned preparation method, one of preferred be: (card pool nurse 1.0～10.0g) is dispersed in the water, makes its abundant swelling, forms thick glue with ophthalmic gel base.With acid (or alkali) property solution adjust pH to 4～9, the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids and other component add in the thick glue after being dissolved in water for injection respectively, add water to 1000ml, the back sterilization that stirs, packing.
Preferred two are: (card pool nurse 1.0～10.0g) is dispersed in the water jointly with the Radix dactylicapni (Radix Dactylicapnotis) alkaloid, forms thick glue with ophthalmic gel base.Other component adds in the thick glue after being dissolved in water for injection, with acid solution adjust pH to 4～9, adds water to 1000ml, and back sterilization packing stirs.
Preferred three are: (card pool nurse 1.0～10.0g) is dispersed in the water jointly with the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids and other component, forms thick glue with ophthalmic gel base.With alkaline solution adjust pH to 4～9, add water to 1000ml, back sterilization packing stirs.
Preferred four are: (hydroxypropyl emthylcellulose 0.1～1.0g) is dispersed in the water, forms thick glue with ophthalmic gel base.With the acid leach solution Radix dactylicapni (Radix Dactylicapnotis) total alkaloids and other component, add then in the thick glue, mix evenly, add water to 1000ml, back sterilization packing stirs.
Radix dactylicapni (Radix Dactylicapnotis) total alkaloids preparation method of extract:
(1) gets the Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder, make solvent, flood and carry out percolation or reflux, extract, after 12～24 hours with 30%～90% ethanol.Filtrate decompression is concentrated into thick paste (1.1～1.3,70 ℃ of surveys), and reuse chloroform-ethanol (8: 1～1: 8) extracts refining, gets the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids.
(2) or get the Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder, the acid ethanol solution reflux, extract, 2～3 times that adds 8 times of amount pH2～5 of 40%～90%, each 2～3 hours, merge extractive liquid,, filter, filtrate is adjusted to pH value 6～8 with aqueous slkali, and decompression recycling ethanol also is condensed into thick paste, adds 20～30 times of saturated calcium hydroxide aqueous solutions of amount, stir, regulate pH2～4 with dilute sulfuric acid, standing over night is filtered, filtrate is regulated pH value 10～12 with aqueous slkali, being concentrated into relative density is 1.10～1.20 (70 ℃ of surveys), filters precipitation, after the aqueous hydrochloric acid solution dissolving with pH2～5, filter, filtrate is crossed macroporous adsorbent resin H absorption, washes with water to effluent closely colourless earlier, 3～6 times of column volume 50%～90% ethanol elutions of reuse, collect ethanol elution, decompression recycling ethanol obtains Radix dactylicapni (Radix Dactylicapnotis) total alkaloids extract.
The present invention makes this medicament for the eyes for liquid, promptly forms gel and onset in conjunctival sac for a long time when contacting with cation in the tear.Thereby it is strong to have stronger lubricated sense and an adhesion, can increase the contact area and the time of medicine and eye, increases drug absorption, reduces a some medicine number of times, thereby brings into play the therapeutical effect of medicine better.
It is active ingredient that the present invention adopts anti-eyestrain's medicine Radix dactylicapni (Radix Dactylicapnotis) total alkaloids, and adopting water miscible gel is substrate, has formed to have eye slow releasing function and excellent biological compatibility gel.Compare with other eye drop in the market, have slow release, comfortable, the advantage that stimulates little and easy-clear.
(1) assay:
Get this product, shake up, precision is measured 25ml, put in the 100ml separatory funnel, add 1 of hydrochloric acid, extract with chloroform gradation (20,20,15,10ml) jolting, chloroform solution is the washing by same 10ml at every turn, filter with filter paper, it is imitative to put water-bath Back stroke dechlorination, adds ethanol 0.5ml, continues evaporate to dryness, put 80 ℃ of dryings 30 minutes, add glacial acetic acid-acetic anhydride (9: 1) 7ml, the slight fever dissolving is put cold, add mercuric acetate test solution 2ml, shake up, add 1 of crystal violet indicator solution, extremely green with perchloric acid titration liquid (0.1mol/L) titration, and do blank correction, promptly.The perchloric acid titration liquid (0.1mol/L) of every 1ml is equivalent to the Isocorydine hydrochloride (C of 37.75mg
20H
23NO
4HCl).Assay the results are shown in Table 1.
Table 1 Determination of Total Alkaloid is total alkaloid content as a result
The every 1ml of this product contains total alkaloids with Isocorydine hydrochloride (C
20H
23NO
4HCl) meter should be 4.5～5.5mg.
(2) pharmacological evaluation
1, to the influence of lactic acid dehydrogenase activity in the lagophthalmos I-CB flesh: 20 rabbit, divide 4 groups at random, every group of 5 animals, 10 eyes.Grouping gives normal saline, with medicament for the eyes gel of the present invention and ZHENSHIMING DIYANYE, equal every 0.1ml, eye drip 3 times/day, 2 weeks of successive administration.30min after the last administration puts to death animal, wins I-CB flesh, surveys lactic acid dehydrogenase (LDH) activity in the I-CB flesh by microcolorimetry.The results are shown in Table 2.
The influence of lactic acid dehydrogenase activity in the table 2 pair lagophthalmos I-CB flesh
Statistical result shows that gel for eye use of the present invention can significantly improve lactic acid dehydrogenase activity in the lagophthalmos I-CB flesh (P＜0.01), and curative effect obviously is better than matched group.
2, to the influence of zinc microelement content in the lagophthalmos tissue: 15 rabbit are divided into 3 groups at random.Give normal saline (5), ZHENSHIMING DIYANYE (5) and gel for eye use of the present invention (5) respectively, equal every 0.1ml, eye drip 3 times/day, in 2 weeks of successive administration, 30min puts to death animal after the last administration, wins eyeball and with normal saline flushing.Extract aqueous humor, cut open and get cornea, I-CB flesh and crystal.Measure the content (μ g/g tissue) of zinc element in the above-mentioned tissue with plasma emission spectrometry.The results are shown in Table 3.
Table 3 pair lagophthalmos is organized the influence (μ g/g tissue) of zinc element content
Annotate: compare with the normal saline group: ※ P＜0.05 ※ ※ P＜0.01
Lactic acid dehydrogenase is one of important enzyme of human body, is distributed widely among the various tissues, and its major function is the anerobic glycolysis of involved in sugar, produces ATP.ATP and can expand peripheral vessel except that energy is provided, blood circulation promoting, thus improve the function of retina and optic nerve.All useful both at home and abroad in recent years ATP treats bathomorphic report.Gel for eye use of the present invention can improve lactic acid dehydrogenase activity in the ocular tissue.Element zinc is participated in the activity of a series of important meals enzymes, and it is exactly a kind of zinc enzyme that aqueous humor is had the carbonic anhydrase of material impact, and the inhibitor of this enzyme can reduce the formation of 50～60% aqueous humors.Zinc also participates in the activity of ethanol dehydrogenase and retinol reductase in the retina, makes retinal regeneration, and directly acts on amphiblestroid neurocyte.
(3) clinical experiment
1, clinical case: 40 examples are organized in treatment, and 74, male 21 examples, women 19 examples, 17～68 years old age, right eye 4 examples, left eye 2 examples, all the other are the eyes patient; Matched group 30 examples, 58, male I3 example, women 17 examples, 18～66 years old age, right eye 1 example, left eye 1 example surplusly is the eyes patient.
2, Therapeutic Method: test group, usage: eye drip, one time 1～2,3 times on the one; Or one time 1～2, close order after dripping and had a rest 5 minutes, drip continuous five times again.When vision restoration to 1.0 is above, can reduce 30 days courses of treatment as one feels fit.Matched group: ZHENSHIMING DIYANYE usage: every day 4～6 times, each 1～2,30 days courses of treatment.
3, clinical treatment result
(1) curative effect determinate standard
1. cure: can adhere to reading or watching fine work attentively more than 1 hour, eyes symptom and General Symptoms disappearance person.2. produce effects: can adhere to reading or watched fine work attentively 30 minutes～60 minutes (moderate and slight disease are lost for transience visual deterioration person, vision restoration after serious symptom is closed order and had a rest 10 minutes), eye symptom and General Symptoms respectively have 2 obvious improvers.3. effective: as to read or watch fine work attentively and prolong (transience visual deterioration person more than 10 minutes before the treatment, vision restoration after serious symptom is closed order and had a rest 20 minutes, vision restoration after moderate disease is closed order and had a rest 10 minutes, light disease disappears), eye symptom and General Symptoms respectively have 2 improvement, or 1 obvious improver is respectively arranged.4. invalid: eye symptom and General Symptoms all do not have the improver before and after the treatment.
(2) therapeutic outcome
74 of treatment groups, effective 63, effective percentage 85.1%; 58 of matched groups, effective 30, effective percentage 51.7%.Two groups of difference significances (P＜0.01).The results are shown in Table 4.
Table 4 treatment group and matched group curative effect statistical analysis
Model case: the king * *, man, 33 years old, office worker, video terminal worker, sensation blurred vision 2 days.Acid is expanded uncomfortable, and twinge is not sometimes desired to open eyes unbearably, and whole body is with agitation, sleeplessness, dizziness, bitter taste.Western medicine diagnose: on inspection, eye conjunctiva mild hyperaemia, eye is blushed swollen, gets rid of other ophthalmic, is diagnosed as asthenopia.Give this preparation eye drip, every day 4～6 times, each 1～2.Treat after 1 month, conscious eye is dry and astringent, scorching hot, order expands, and symptoms such as pain, agitation, sleeplessness, dizziness disappear clinical cure substantially.
(4) specific embodiment
Embodiment one
A kind of preparation method for the treatment of asthenopic Chinese medicine preparation, to make 1000ml is that example is that the 5g Radix dactylicapni (Radix Dactylicapnotis) total alkaloids, 3g ophthalmic gel base carbomer and an amount of water for injection are mixed, stir into gel, with the sodium hydroxide adjust pH to 4-9, add the injection water to 1000ml, sterilization, packing is finished product.
Embodiment two
A kind of preparation method for the treatment of asthenopic Chinese medicine preparation, 1000ml is an example with preparation, be that Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 5g, ophthalmic gel base carbomer 10g and an amount of water for injection are mixed, stir into gel, to 4-9, add the injection water to 1000ml, sterilization with 10% hydrochloric acid solution or sodium hydroxide solution adjust pH, packing is finished product.
Embodiment three
A kind of preparation method for the treatment of asthenopic Chinese medicine preparation, 1000ml is an example with preparation, is Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 5g, ophthalmic gel base carbomer 18g and an amount of water for injection are mixed, stir into gel, adjust pH adds the injection water to 1000ml to 4-9, sterilization, packing is finished product.
Embodiment four
Get Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder 500g or 1000g, with 60%, 80%, 90% ethanol is made solvent, floods to carry out the gradient percolation after 24 hours, and the liquid color is light to filtering.The liquid of filtering is evaporated to thick paste (1.1～1.3,70 ℃ of surveys), and reuse chloroform-ethanol (8: 1) extracts refining total alkaloids.
Embodiment five
Get Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder 500g or 1000g, add 8 times of amounts 60%, 80%, the acid ethanol solution reflux, extract, of 90% pH2～5 3 times, each 2.0 hours, merge extractive liquid, filtered, filtrate is adjusted to pH value 6～8 with aqueous slkali, decompression recycling ethanol also is condensed into thick paste, adds 20～30 times of saturated calcium hydroxide aqueous solutions of amount, stirs, regulate pH2～4 with dilute sulfuric acid, standing over night is filtered, and filtrate is regulated pH value 10～12 with aqueous slkali, being concentrated into relative density is 1.10～1.20 when surveying for 70 ℃, filter, after the aqueous hydrochloric acid solution dissolving of precipitation with pH2～5, filter, filtrate is crossed macroporous adsorbent resin H absorption, wash with water to effluent closely colourlessly earlier, 3～6 times of column volume 50～90% ethanol elutions of reuse are collected ethanol elution, decompression recycling ethanol obtains Radix dactylicapni (Radix Dactylicapnotis) total alkaloids extract.
Embodiment six:
Arbitrary total alkaloids in the various embodiments described above is extracted medicine, add Borax 2.8g, boric acid 10.5g, heating for dissolving was boiled 5～15 minutes, put coldly, filtered with microporous filter membrane (0.22mm), added the injection water to 1000ml, was eye drop of the present invention.
Embodiment seven: arbitrary total alkaloids in the various embodiments described above is extracted medicine, add injection water 800ml dissolving; Add the about 8.5g of sodium chloride, the osmotic pressure of regulator solution is regulated the pH value of medicinal liquid between 4.0～7.0 with 10% hydrochloric acid solution or sodium hydroxide solution; Add benzalkonium chloride, consumption is 0.005%; Add hydroxypropyl emthylcellulose 0.2g, add the injection water to 1000ml, packing promptly gets gel for eye use.
Embodiment eight:
Get carbomer 2.0g, add an amount of water for injection, add antiseptic, antioxidant and isotonic agent again, heating makes it dissolving, and the reuse sodium hydroxide is regulated pH to 6.0～7.0, gets carbomer colloidal sol.Stir in the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids that adds above-mentioned steps, regulates pH value to 6.0～8.0, adds water for injection to 1000ml, heat sterilization, and cooling, packing promptly gets gel for eye use.
Claims (6)
1, the asthenopic Chinese medicine preparation of a kind of treatment, it is characterized in that with 1000ml being example, mainly be to mix by Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 1-10g, ophthalmic gel base 0.1-20g and suitable quantity of water, stir, with pH regulator agent adjust pH to 4-9, add the injection water to 1000ml, stirring is prepared into gel promptly.
2, the asthenopic Chinese medicine preparation of a kind of treatment according to claim 1, the preparation method that it is characterized in that the described Radix dactylicapni (Radix Dactylicapnotis) total alkaloids is to get the Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder, make solvent with 30%～90% ethanol, flood and carry out percolation or reflux, extract, after 12～24 hours, filtrate decompression is concentrated into thick paste, relative density is 1.1～1.3 70 ℃ of surveys, and is refining in order to the chloroform-ethanol extraction of charge ratio preparation in 8: 1～1: 8, gets the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids.
3, the asthenopic Chinese medicine preparation of a kind of treatment according to claim 1, the preparation method that it is characterized in that the described Radix dactylicapni (Radix Dactylicapnotis) total alkaloids is to get the Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder, the acid ethanol solution reflux, extract, 2～3 times that adds 8 times of amount pH2～5 of 40%～90%, each 2～3 hours, merge extractive liquid,, filter, filtrate is adjusted to pH value 6～8 with aqueous slkali, and decompression recycling ethanol also is condensed into thick paste, add 20～30 times of saturated calcium hydroxide aqueous solutions of amount, stir, regulate pH2～4, standing over night with dilute sulfuric acid, filter, filtrate is regulated pH value 10～12 with aqueous slkali, and being concentrated into relative density is 1.10～1.20 when surveying for 70 ℃, filters, after the aqueous hydrochloric acid solution dissolving of precipitation with pH2～5, filter, filtrate is crossed macroporous adsorbent resin H absorption, washes with water to effluent closely colourless earlier, 3～6 times of column volume 50%～90% ethanol elutions of reuse, collect ethanol elution, decompression recycling ethanol obtains Radix dactylicapni (Radix Dactylicapnotis) total alkaloids extract.
4, the asthenopic Chinese medicine preparation of a kind of treatment according to claim 1 is characterized in that described ophthalmic gel base is selected from carbomer, methylcellulose, hydroxy methocel, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, crospolyvinylpyrrolidone, poly-ethanol, Polyethylene Glycol.
5, a kind of preparation method for the treatment of asthenopic Chinese medicine preparation according to claim 1, it is characterized in that, 1000ml is an example with preparation, the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids 5.0 ± 4.0g, ophthalmic gel base 18g and an amount of water for injection are mixed, stir, transfer pH value to 4-9, add the injection water to 1000ml, sterilization, packing is finished product.
6, the asthenopic Chinese medicine preparation of a kind of treatment according to claim 2, it is characterized in that getting Radix dactylicapni (Radix Dactylicapnotis) medicinal material coarse powder 500g or 1000g, with 60%, 80%, 90% ethanol is made solvent, flood and carry out the gradient percolation after 24 hours, the liquid color is light to filtering, and the liquid of filtering is evaporated to thick paste, and recording relative density under 70 ℃ is 1.1～1.3, chloroform-ethanol extraction in order to charge ratio preparation in 8: 1～1: 8 is refining, gets the Radix dactylicapni (Radix Dactylicapnotis) total alkaloids.
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| CN200610046146A CN100577187C (en) | 2006-03-23 | 2006-03-23 | Chinese medicine preparation for treating eye fatigue and its preparing process |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104688931A (en) * | 2015-04-02 | 2015-06-10 | 张玉雯 | Medicine composition for relieving eyestrain and preparation method of medicine composition |
| CN114504425A (en) * | 2020-11-16 | 2022-05-17 | 湖北舒邦药业有限公司 | Cold compress patch preparation method, cold compress patch and application method thereof |
| CN114712418A (en) * | 2022-04-08 | 2022-07-08 | 西安军科视光科技研究院有限责任公司 | Ophthalmic gel for treating myopia |
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2006
- 2006-03-23 CN CN200610046146A patent/CN100577187C/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 异可利定治疗假性近视疗效分析. 曾令柏，程玉霞，毛选文，邢陇平，樊兴全.昆明医学院学报，第3卷第4期. 1982 |
| 异可利定治疗假性近视疗效分析. 曾令柏，程玉霞，毛选文，邢陇平，樊兴全.昆明医学院学报，第3卷第4期. 1982 * |
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Effective date of registration: 20120118 Address after: Hi Tech road Shenyang city Liaoning province 110179 Hunnan New District No. 15 Patentee after: Shenyang Shuangding Technology Co., Ltd. Address before: Hi Tech road Shenyang city Liaoning province 110179 Hunnan New District No. 15 Patentee before: Shuangding Pharmaceutical Co., Ltd, Shenyang |
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Address after: Hi Tech road Shenyang city Liaoning province 110179 Hunnan New District No. 15 Patentee after: Shuangding Pharmaceutical Co., Ltd, Shenyang Address before: Hi Tech road Shenyang city Liaoning province 110179 Hunnan New District No. 15 Patentee before: Shenyang Shuangding Technology Co., Ltd. |
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