CN105012404A - Eye drop for treating xerophthalmus and preparation method of eye drop - Google Patents
Eye drop for treating xerophthalmus and preparation method of eye drop Download PDFInfo
- Publication number
- CN105012404A CN105012404A CN201410165886.5A CN201410165886A CN105012404A CN 105012404 A CN105012404 A CN 105012404A CN 201410165886 A CN201410165886 A CN 201410165886A CN 105012404 A CN105012404 A CN 105012404A
- Authority
- CN
- China
- Prior art keywords
- parts
- water
- add
- extract
- times amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an eye drop for treating xerophthalmus and a preparation method. The eye drop is prepared from the following raw materials and auxiliary materials in parts by weight: 130-170 parts of an extract containing bear gall powder, 1.5-3.3 parts of borneol, 1-2 parts of a bacteriostatic agent, 6-10 parts of a solubilizer, 40 parts of sodium borate and 10 parts of boric acid. According to the physical and chemical properties of chemical components contained in the medicinal material in the formula, use of volatile oil is removed; the dosage of the borneol and the bear gall powder is adjusted; the borneol and the bear gall powder are added in different manners; muddy opalescence and the like caused by a conventional bear gall powder adding method are reduced; the medicinal composition is ensured; meanwhile, the preparation directly acts on the medication part; the dosage is greatly reduced; the onset time of the medicine is quickened; and the curative effect is improved.
Description
Technical field
The invention belongs to field of traditional Chinese, be specifically related to a kind of eye drop and the preparation method that are used for the treatment of xerophthalmia.
Background technology
Basis-reinforcing eyesight-improving granule is oral formulations, be made up of Flos Carthami, Fructus Chebulae, Corydalis impatiens (Pall.) Fisch., Flos Caryophylli, Borneolum Syntheticum, Fel Ursi powder 6 taste medical material and sucrose, have and regulate gas of bursting, function of improving eyesight, for the fuzzy viewing that routed gas causes, conjunctival congestion is dry and astringent waits disease, and clinical efficacy is definite, its applied code is WS-10485 (ZD-0485)-2002, side in Flos Carthami and Corydalis impatiens (Pall.) Fisch. promoting blood circulation to remove blood stasis, heat clearing away resolving depression, stimulate the menstrual flow promoting the circulation of QI; The spleen invigorating of Flos Caryophylli regulating QI and lowering the adverseness; Borneolum Syntheticum is sensible, resolving depression, removing nebula, improving eyesight; Fel Ursi liver heat removing and eyesight improving; Fructus Chebulae balances the property of medicine, and pathogenic fire reducing profit liver, wherein the Main Function of Flos Caryophylli is regulating QI and lowering the adverseness spleen invigorating.
Patent document " a kind of basis-reinforcing eyesight-improving dropping pill for the treatment of oculopathy and preparation method thereof " (CN1709419, hereinafter referred to as " basis-reinforcing eyesight-improving dropping pill application ") discloses basis-reinforcing eyesight-improving dropping pill, by Borneolum Syntheticum, Fel Ursi powder dissolve with ethanol; Flos Caryophylli, Flos Carthami extract volatile oil; Drying and crushing after Fructus Chebulae, the purple water extract-alcohol precipitation in the north to the Great Wall, obtains extract after spraying into the volatile oil containing the ethanol of Borneolum Syntheticum, Fel Ursi powder, extraction; Make basis-reinforcing eyesight-improving dropping pill after adding the substrate of drop pill, define the usage ratio of principal agent and adjuvant simultaneously.
Basis-reinforcing eyesight-improving formula is mainly used in ocular disease; and basis-reinforcing eyesight-improving granule or basis-reinforcing eyesight-improving dropping pill are oral formulations; eye focus could be arrived through steps such as gastrointestinal absorption and play a role; first pass effect makes agent disrupts serious and whole body distribution after drug absorption; eye focus blood drug level is on the low side; therefore basis-reinforcing eyesight-improving formula is made eye drop local application, be more conducive to medicine and play curative effect.In addition, first to Flos Carthami vapor extraction volatile oil in basis-reinforcing eyesight-improving granule and basis-reinforcing eyesight-improving dropping pill application, then extract flavonoid, through long high temperature, the effective ingredient flavonoid loss in Flos Carthami is very large.
Compositions in basis-reinforcing eyesight-improving granule or basis-reinforcing eyesight-improving dropping pill application is made eye drop, not only needs adjustment osmotic pressure, pH value to appropriate numerical value, also need to solve adding and extract zest problem of Fel Ursi powder.Eye drop made by medicine containing Fel Ursi powder, and customary preparation methods adds in the solution prepared after Fel Ursi powder is dissolved in ethanol again, but obtained eye drop easily appears cloudy precipitate; Further, the raw material of basis-reinforcing eyesight-improving granule or drop pill is without process, and zest is excessively strong, is not suitable for eyes local application.
In addition, the consumption of eye drop is far smaller than the dosage of oral formulations, also needs suitably to adjust for raw material.
Basis-reinforcing eyesight-improving preparation is made eye drop, not yet finds precedent or bibliographical information at present.
Summary of the invention
For overcoming the deficiencies in the prior art, the invention provides a kind of eye drop being used for the treatment of xerophthalmia; Present invention also offers the preparation method of this eye drop.
For achieving the above object, the present invention adopts following technical proposals:
Be used for the treatment of an eye drop for xerophthalmia, the weight portion of supplementary material is composed as follows:
Containing extract 130-170 part of Fel Ursi powder
Borneolum Syntheticum 1.5-3.3 part
Antibacterial 1-2 part
Solubilizing agent 6-10 part
Borax 40 parts
Boric acid 10 parts
Volumetric concentration 80-95% ethanol 6-10 part
Water for injection is appropriate
Make 5000 times amount volumes altogether
Extract wherein containing Fel Ursi powder is prepared from by the following method:
Get Flos Carthami 340-400 part, Fructus Chebulae 340-400 part, Corydalis impatiens (Pall.) Fisch. 110-130 part by weight, add volume ratio 65-95% ethanol to extract 2-4 time in 45-80 DEG C, add medical material weight 6-10 times amount volume at every turn, each extraction time 1-4 hour, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 3-5 times amount volume, obtain alcohol aqueous suspension; Get Fel Ursi powder 8-12 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 10-30 minute, leave standstill 12-48 hour, filter, filtrate reduced in volume, spraying dry, must containing the extract of Fel Ursi powder.
The present invention is preferred, a kind of eye drop being used for the treatment of xerophthalmia, and the extract wherein containing Fel Ursi powder is prepared from by the following method:
Get 364 parts, Flos Carthami, Fructus Chebulae 364 parts, Corydalis impatiens (Pall.) Fisch. 121 parts by weight, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 8 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 4 times amount volumes, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, must containing the extract of Fel Ursi powder.
The present invention is preferred, a kind of eye drop being used for the treatment of xerophthalmia, and the weight portion of supplementary material is composed as follows:
Containing the extract 146 parts of Fel Ursi powder
Borneolum Syntheticum 2.5 parts
Antibacterial 1.5 parts
Solubilizing agent 7.5 parts
Borax 40 parts
Boric acid 10 parts.
Volumetric concentration 80-95% ethanol 7.5 parts
Water for injection is appropriate
Make 5000 times amount volumes altogether
A kind of eye drop being used for the treatment of xerophthalmia of the present invention, wherein antibacterial is selected from one or both in benzene Zha Lvte, benzene bundle bromine spy, is preferably benzene Zha Lvte; Solubilizing agent be selected from PEG400, Macrogol 600 one or both, be preferably Macrogol 600; Ethanol contend concentration is preferably 95%.
Supplementary material of the present invention is bought without the market that is of special instruction.
Be used for the treatment of a preparation method for the eye drop of xerophthalmia, step is as follows:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 340-400 part, Fructus Chebulae 340-400 part, Corydalis impatiens (Pall.) Fisch. 110-130 part by weight, add volume ratio 65-95% ethanol to extract 2-4 time in 45-80 DEG C, add medical material weight 6-10 times amount volume at every turn, each extraction time 1-4 hour, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add 3-5 times amount volume water, obtain alcohol aqueous suspension; Get Fel Ursi powder 8-12 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 10-30 minute, leave standstill 12-48 hour, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: get 1.5-3.3 part Borneolum Syntheticum by weight, add 6-10 part volumetric concentration 80-95% ethanol and make dissolving, then add the solubilizing agent of 6-10 part, filter to obtain Borneolum Syntheticum solution for standby; Join in the water for injection of 200-4500 times amount volume by the extract containing Fel Ursi powder of 130-170 weight portion, stirring and dissolving, filters to obtain water precipitating thing solution; Getting above-mentioned Borneolum Syntheticum solution joins in water precipitating thing solution, and limit edged stirs, then adds the water for injection of 100-4400 times amount volume, add 40 parts of Boraxs, 10 parts of boric acid and 1-2 part antibacterial again, be stirred to dissolve, inject water to 5000 times amount volumes, mixing, filters, to obtain final product.
The present invention is preferred, a kind of preparation method being used for the treatment of the eye drop of xerophthalmia, and step is as follows:
1) preparation is containing the extract of Fel Ursi powder: get 364 parts, Flos Carthami, Fructus Chebulae 364 parts, Corydalis impatiens (Pall.) Fisch. 121 parts by weight, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 8 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 4 times amount volumes, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: get 2.5 parts of Borneolum Syntheticums by weight, add 7.5 parts of volume ratio 95% ethanol and make dissolving, then add 7.5 parts of solubilizing agents, filter to obtain Borneolum Syntheticum solution for standby; Join in the water for injection of 2500 times amount volumes by the extract containing Fel Ursi powder of 146 weight portions, stirring and dissolving, filters to obtain water precipitating thing solution; Getting above-mentioned Borneolum Syntheticum solution joins in water precipitating thing solution, and limit edged stirs, then adds the water for injection of 2000 times amount volumes, in solution, add 40 parts of Boraxs, 10 parts of boric acid and 1.5 parts of antibacterial again, be stirred to dissolve, inject water to 5000 times amount volumes, mixing, filters, to obtain final product.
Times amount volume of the present invention refers to the corresponding relation of weight and volume, and unit is ml/g or L/kg.
Compared with prior art, advantage is as follows in the present invention:
1. the present invention finds, in basis-reinforcing eyesight-improving oral formulations, volatile oil composition directly acts on eyes local time, zest is too large, do not affect the treatment after removal, thus, invention removes the Flos Caryophylli in prescription, abandoned the extraction to Flos Caryophylli, Flos Carthami volatile oil and use, decrease the destruction to safflower flavonoids simultaneously.
2. in the former side of basis-reinforcing eyesight-improving, the use amount of Borneolum Syntheticum is oral formulations, and be not suitable for eye drop, the present invention have adjusted the consumption of Borneolum Syntheticum.In addition, the present invention also improves the feed postition of wherein Fel Ursi powder, adds the consumption of Fel Ursi powder to offset refining losses, and eliminates the problem that easily appears cloudy precipitate that eye drop uses Fel Ursi powder to cause.
3. the present invention have selected Borax-boric acid system through great many of experiments is adjuvant, both as osmotic pressure regulator, doubles as pH adjusting agent again, and the present invention also have selected and examines antibacterial and solubilizing agent.After testing, eye drop of the present invention meets the every regulation of pharmacopeia to eye drop.
4. the eye drop preparation prepared of the present invention is compared with oral formulations, not only greatly reduces drug dose, and directly acts on lesions position due to medicine, accelerates onset time, improves curative effect.
Detailed description of the invention
Following embodiment and experimental example are used for further illustrating but are not limited to the present invention.
Experimental example 1, extraction process are tested
The mode that this experiment adopts single factor test and orthogonal test to combine, (be called for short: HSYA) with S-A Hydroxysafflor yellow A, the weighted average coefficients of total alkaloids is inspection target, to the kind (water of solvent, ethanol), solvent concentration (65-95%), consumption (6-10 doubly), extraction time (1-4h), number of times (2-4 time), temperature controls factors such as (45-90 DEG C) and is in optimized selection, find Extracting temperature, solvent consumption and extraction time are larger to extraction Influence on test result, thus screening determines optimum extraction process and is: medical material adds 90% ethanol extraction 2 times, first time adds 8 times amount, extract 3 hours, second time adds 8 times amount, extract 2 hours, Extracting temperature controls at 60 DEG C, the yield that technique is extract obtained is according to this 14.3%.
Experimental example 2: water precipitating technological experiment
Take Flos Carthami 91g, Fructus Chebulae 91g, Corydalis impatiens (Pall.) Fisch. 30.25g, add 90% ethanol extraction 2 times, first time adds 8 times amount volumes, extracts 3 hours, second time adds 8 times amount volumes, extract 2 hours, filter, filtrate recycling ethanol, when reconcentration to relative density is 1.25 (50 DEG C of surveys), be divided into 3 parts, first part adds 3 times of water gagings, and second part adds 4 times of water gagings, 3rd part adds 5 times of water gagings, join in above-mentioned alcohol aqueous suspension respectively, stir, leave standstill 48 hours, filter, concentrating under reduced pressure, measures content, calculates the gallic acid rate of transform.
Table 1 water precipitating industrial analysis table
Result shows, and add 3 times amount volume water, content is slightly low, and more difficult when filtering, 4 times and 5 times amount volume water, and content difference is little, and when considering to add 5 times amount volume water, concentration time will extend, and therefore select the water adding 4 times amount volumes to carry out water precipitating.
Experimental example 3, Fel Ursi powder processing mode are tested
Fel Ursi powder is water soluble ingredient, after conventional method and documents and materials method are and add a certain amount of water dissolution, directly carries out next step operation.
The present invention adopts said method to find, carries out next step preparation, unavoidably become turbid after Fel Ursi powder water dissolution, adopts high speed centrifugation mode also cannot avoid.
The present invention found through experiments, and to join in ethanol extraction aqueous precipitation again after Fel Ursi powder water dissolution, and after filtering, reconcentration is to dry, with water dissolution, then adds corresponding adjuvant, makes eye drop preparation, can solve the problem, specific experiment and result as follows:
Mother solution: add suitable quantity of water after alcohol extracting-water precipitating thing drying prepared by experimental example 2 and dissolve.
Technique one: get Fel Ursi powder aqueous solution (1ml is containing getting Fel Ursi powder 0.05g) 4ml and join in 80ml mother solution, mixing, shakes up, adds water and supply 100ml, places 48h, observes solution character and detects the amount retained of wherein Fel Ursi powder.
Technique two: get Fel Ursi powder aqueous solution (1ml is containing getting Fel Ursi powder 0.05g) 4ml, add 2ml Macrogol 600 (PEG600) 4ml, mix homogeneously, join in 80ml mother solution, mixing, shakes up, adds water and supply 100ml, place 48h, observe solution character and detect the amount retained of wherein Fel Ursi powder.
Technique three: getting Fel Ursi powder aqueous solution (1ml is containing getting Fel Ursi powder 0.05g) 4ml, adding 2ml Tween 80 2ml, mix homogeneously, join in 80ml mother solution, mixing, shakes up, add water and supply 100ml, place 48h, observe solution character and detect the amount retained of wherein Fel Ursi powder.
Technique four: get Fel Ursi powder 0.5g and first add 2ml water dissolution, adds in 80ml alcohol aqueous suspension (i.e. experimental example 2 obtained), stirs, place 48h, observes solution character and detects the amount retained of wherein Fel Ursi powder.
Table 2 Fel Ursi powder processing mode is screened
Contained Fel Ursi amount/theoretical Fel Ursi content * 100% in medicinal liquid after 2d amount retained (%)=2 day
Conclusion: experimental result shows, be dissolved in water by Fel Ursi powder and join different extraction in solution again, there is turbid phenomenon in technique one and technique three, technique two occurs turbid phenomenon after placing 48h at once; And after Fel Ursi powder and ethanol extract being merged, carrying out water precipitating process again, gained solution is placed and is not occurred deposited phenomenon more than 48h, and does not add any adjuvant (Polyethylene Glycol, Tween 80), for later stage preparation process provides convenient.In 48h amount retained, the result of technique four reaches more than 90%.Meanwhile, in view of Fel Ursi powder is lost (about 10%) in the process, so the present invention's amount of Fel Ursi powder on formula brings up to 110% of former side amount.
Experimental example 4, eye drop preparation technological experiment
(1) the adding of Borneolum Syntheticum
According to the physicochemical property of Borneolum Syntheticum, select ethanol as carrier solvent, and investigate the volumetric concentration that have selected ethanol.
Found that, the ethanol of 80-95% concentration is good for the solute effect of Borneolum Syntheticum, the especially ethanol of 95%, and Borneolum Syntheticum dissolves rapidly, and without separating out, therefore the feed postition of Borneolum Syntheticum is preferably: add after using the dissolve with ethanol of 95% to form solution again.
(2) selection of carrier solvent
According to the physicochemical property of said extracted raw material, select water as carrier solvent, and adjust the use amount of Borneolum Syntheticum.Carry out following test:
Take 1g Borneolum Syntheticum, add 3g95% ethanol and make dissolving, then add 3g Macrogol 600, filter for subsequent use.
Take the extract 3.2g containing Fel Ursi powder, add 50ml water for injection, stirring and dissolving, getting 0.35g Borneolum Syntheticum solution joins in alcohol aqueous suspension, limit edged stirs, and injects and makes into 100ml with water, obtains brown color supernatant liquid (surveying medicinal liquid pH value is 3.43), let cool rear clarity good, 4 DEG C of low temperature place and spend the night after clarity good.Determine the solvent using water as this product.(3) selection of pH adjusting agent
The pH value of normal eye tolerance is 5.0 ~ 9.0, and when pH value 6.0 ~ 8.0, eyes are without sense of discomfort, and eye is more responsive to alkalescence, and comparatively strong acid more can make ocular injury.By determining prescription preparating liquid, recording pH value is about 3.4, does not set in a liquid pH value range (6.0 ~ 8.0) at us, so about tentatively determining to regulate medicinal liquid pH value to 6.5 with Borax and boric acid.
Table 3 observes pH value synopsis in three months
As seen from the experiment, during by boric acid-Borax buffer salt system adjust ph, the pH value of system remains unchanged substantially, and this pH value is applicable to eye drop.
(4) selection of antibacterial
The antibacterial that eye drop is conventional is benzalkonium chloride and benzalkonium bromide, the two character, act on similar.The concentration that the present invention investigates antibacterial for benzalkonium chloride is selected.Adopt not commensurability benzalkonium chloride to carry out the preparation of sample, by three months study on the stability, observe its fungistatic effect quality, determine antibacterial consumption.
The selection of table 4 antibacterial consumption
Experimental result shows, and adopts the benzalkonium chloride of concentration more than 0.02% as antibacterial, does not occur mildew phenomena, consider the safety of stability of drug products and patient medication, determine the optimum consumption selecting the benzalkonium chloride of 0.03% as antibacterial within 3 months.
(5) selection of solubilizing agent
Tween 80 and PEG400, PEG600 has been investigated on the impact of Borneolum Syntheticum solubilizing effect in experimentation, when result adds Tween 80, solution neutrality carves existing turbid phenomenon, and solution clarification when doing solubilizing agent with PEG400 or PEG600, so select PEG400 or PEG600 as solubilizing agent, the solution configured is added PEG400 or PEG600 according to following table consumption, observes solubilizing effect.
Table 5PEG400 and PEG600 solubilizing effect contrast table
Result shows, and when PEG400 or PEG600 consumption accounts for more than 0.1% of total amount of liquid, solution is clarified, and deposit-free, therefore select PEG400 or PEG600 to be solubilizing agent, optimum consumption is 0.15%.
(6) selection of osmotic pressure regulator
The adaptable osmolarity ranges of eyeball is equivalent to the sodium chloride solution of 0.6%-1.5%, just has obvious discomfort more than 2%.Hypisotonic solution should be adjusted to isosmotic solution with suitable material.The present invention maintains pH value with Borax-boric acid (volume ratio 4:1) buffer salt system, and for reducing supplementary product consumption, the present invention continues to select Borax-boric acid (4:1) buffer salt system to regulate osmotic pressure.
Table 6 osmotic pressure reconciliation statement
Conclusion: can be obtained by test data, when the consumption of Borax-boric acid (4:1) is 1.0%, the osmotic pressure of the osmotic pressure of gained finished product relatively human eye tear, so the consumption selecting Borax-boric acid (4:1) is 1.0%.
(7) stability experiment
Get the sample prepared by the formulation and technology determined appropriate, set high temperature (60 DEG C) respectively, low temperature (4 DEG C) and lower 10 days of high light (4500Lx) condition, detect respectively at sampling in 0,5,10 day, investigate the stability of sample,
Table 7 influence factor result of the test
Conclusion: this product is placed after 10 days respectively under high temperature (60 DEG C), low temperature (4 DEG C) and illumination (4500lx) condition, every quality index is without significant change, illustrate that the sample quality prepared by this formulation and technology is stablized, therefore determine that this formulation and technology is final formulation and technology.
Experimental example 5, lagophthalmos irritation test
One, test material:
1, medicine: 10% Sodium fluorescein, brownish red clear liquid, specification 5ml:500mg, lot number 210486, cardinalhealth manufacturing services BV produces.
2, tested material preparation:
Without medicine adjuvant: get benzalkonium chloride 1.5g, PEG6007.5g, 95% ethanol 7.5g, Borax 40g, boric acid 10g, water for injection in right amount, make 5000ml, to obtain final product.
Containing volatile oil eye drop: prepare volatile oil by basis-reinforcing eyesight-improving dropping pill application, obtain 5.5ml, use β-cdinclusion in conventional manner, separately get containing extract 146g, the Borneolum Syntheticum 2.5g of Fel Ursi powder, benzalkonium chloride 1.5g, PEG6007.5g, 95% ethanol 7.5g, Borax 40g, boric acid 10g, water for injection appropriate, make 5000ml, to obtain final product.
Non-volatile oily eye drop: prepared by embodiment 1.
3, animal: new zealand rabbit 25, male and female dual-purpose, female person is without pregnant, and body weight 2.5-3.0kg, the anti-Pharmaceutical Group in Shandong, Shandong provides, the quality certification number: Shandong kinoplaszm word D20120922.
Instrument: slit lamp microscope, model YT-02, instrument platform: Suzhou Medical Instruments Factory produces.
Two, experimental technique
1, animal preliminary election: perusal: cornea is without muddiness.Conjunctiva is without hyperemia, edema and secretions, and pupil is circular, and both sides etc. are large, good to luminous reflectance.Slit lamp examination: corneal transparency, without nebula, speckle nebula; Iris texture is clear, without congestion and edema.Fluorescent staining: l0% Sodium fluorescein, faces the used time with normal saline dilution 5 times.It is clean with normal saline flushing after every lagophthalmos drips.Observing the non-tinter of cornea is that cornea is normal.Through above-mentioned select anophthalmia disease in advance and healthy rabbits 25 only for this test.
2, eye irritation test
2.1 short-term multiple dosings are to Eye irritation: select adult healthy new zealand rabbit 10, male and female dual-purpose, body weight 2.5 ~ 3.0kg, are divided into volatilization line of oils and experimental group 2 groups at random, cut off by every treated animal eyelash.Tested material (0.1ml/ eye) is all dripped in eye conjunctival sac on the left of volatilization line of oils every animal.Dripping without medicine adjuvant in the eye conjunctival sac of right side is contrast; Tested material (0.1ml/ eye) is all dripped in eye conjunctival sac on the left of experimental group every animal.Dripping without medicine adjuvant in the eye conjunctival sac of right side is contrast; Oppress nasolacrimal duct during each administration, and make the passive closed 5 ~ l0s of eye.Each group of all every 15min eye dripping once.Successive administration 2h.The local excitation response situation of 6h, 24h, 48h, 72h to 7d eye after record administration.
2.2 long term administration eye irritant tests: select adult healthy new zealand rabbit 10, male and female dual-purpose, body weight 2.5 ~ 3.0kg, are divided into volatilization line of oils and experimental group 2 groups at random, are cut off by every treated animal eyelash.Tested material (0.1ml/ eye) is all dripped in eye conjunctival sac on the left of volatilization line of oils every animal.Dripping without medicine adjuvant in the eye conjunctival sac of right side is contrast; Tested material (0.1ml/ eye) is all dripped in eye conjunctival sac on the left of experimental group every animal.Dripping without medicine adjuvant in the eye conjunctival sac of right side is contrast.Oppress nasolacrimal duct during each administration, and make the passive closed 5 ~ l0s of eye.Every day 5 times, successive administration is observed weekly and is recorded to off-test for 4 weeks after on-test.
3, number of winks measures: get preliminary election healthy animal 5.Male and female dual-purpose.Every treated animal eyelash is cut off.Tested material (0.1ml/ eye) is all dripped in eye conjunctival sac on the left of every animal.Dripping without medicine adjuvant in the eye conjunctival sac of right side is contrast.Nasolacrimal duct is oppressed during each administration. and make the passive closed 5 ~ 10s of eye, immediately record number of winks in l0min.Calculate 5 animal images of left and right eyes average blink number of times respectively.Evaluate medicine to the zest (number of winks at most zest is large) of eye.
Three, result
1, eye irritation test: be namely added by the score value of every horn film, iris and conjunctiva irritant reaction is the total mark that an animal subject Eye irritation reacts.The total mark of the irritant reaction of each animal subject divided by number of animals, be exactly the last score value of this tested material to eye irritation.Integration 0 ~ 3 is nonirritant, and integration 4-8 is slight zest, and integration 9-12 is moderate zest, and integration is greater than 13 for strong and stimulating.The results are shown in Table 8.
Table 8 irritation test result
| Without medicine adjuvant n=5 | Volatilization line of oils n=5 | Experimental group n=5 | |
| Cornea | 0 | 2.2±0.84 | 0 |
| Iris | 0 | 2.8±0.84 | 0 |
| Conjunctiva | 0 | 5.8±1.92 | 0.8±0.84 |
| Total mark | 0 | 10.8±2.59 | 0.8±0.84 |
| P value | —— | ＜0.01 | ＞0.05 |
Note: experimental group with compared with medicine adjuvant, P>0.05, statistics zero difference; Volatilization line of oils with compared with medicine adjuvant, P < 0.01, pole significant difference.
By table 8 finding, be shown as moderate zest containing volatile oil eye drop irritant test, especially stronger to conjunctiva zest; Experimental group and without medicine adjuvant group then to lagophthalmos vacuum response.
2, animal number of winks measures: record each treated animal put drops in one's eyes after number of winks in l0min, check through statistical procedures t.The results are shown in Table 9.
Table 9 pair rabbit number of winks measurement result
| Number of winks/10min, n=5 | P value | |
| Without medicine adjuvant group | 7.6±1.14 | —— |
| Experimental group | 7.8±1.10 | ＞0.05 |
Note: experimental group with compared with medicine adjuvant, P>0.05, statistics zero difference.
Result shows: experimental group compares there was no significant difference (P>0.05) with without medicine adjuvant, and eye drops on rabbit nonirritant of the present invention is described.
Four, conclusion
Experiment finds, volatile oil component in basis-reinforcing eyesight-improving is stronger to lagophthalmos zest, for moderate zest, remove the eye drop short-term after volatile oil component repeatedly and long term administration irritant test lagophthalmos is all had no significant effect (P > 0.05), with without medicine adjuvant, no significant difference (P>0.05) is compared to rabbit number of winks.After laboratory animal uses eye drop of the present invention, cornea of both eyes is transparent, and without muddy, iris texture is clear, conjunctiva without hyperemia, without edema, without secretions.
Experimental example 6, to treatment xerophthalmia clinical observation
1, clinical data
With reference to antiperspirant, thanks for your advice awards the diagnostic analysis standard of suggestion in diagnostic criteria, comprises foreign body sensation, sensation of dryness, gargalesthesia, photophobia, furious, not resistance to flue dust etc.(list of references: antiperspirant holds, Zhou Zulian, Zhao Chengrong, the research [J] of score etc. xerophthalmia classification and artificial tear therapeutic evaluation. ophthalmology is studied, and 1994,12 (1): 25-27)
Selected patient 108 example, wherein man 53 example, female 55 example; 25 ~ 75 years old age, average (50.4 ± 7.8) year.Adopt the method for random packet that patient is divided into three groups, treatment group and contrast 1 group, contrast 2 groups of each 36 examples.Between three groups of cases, the data such as sex, age, the course of disease and state of an illness is through statistical procedures, and equal not statistically significant, has comparability.
TCM syndrome standards of grading: adopt symptom integral method
Table 10 xerophthalmia clinical symptoms classification score standard
(list of references: Xie Like, Zhu Zhirong, Zhang Mingming. the clinical research [J] of XIAOYAO POWDER associating SHENGMAI SAN treatment xerophthalmia. Chinese TCM Ophthalmology magazine, 2009,1 (2): 71-73)
2, experimental technique
2.1 Therapeutic Method: treatment group experimenter gives embodiment 1 obtained basis-reinforcing eyesight-improving eye drop, every day 6 times, contrast 1 group of oral former technique basis-reinforcing eyesight-improving granule of experimenter, every day 3 times, each 5g, contrasts 2 groups of oral drop pill prepared according to basis-reinforcing eyesight-improving dropping pill application of experimenter, every day 3 times, each 5g, is used in conjunction 4 weeks.Duration of test is forbidden adding the Pharmaceuticals with close with trial drug effect, if any the complication relevant with disease, all can anti symptom treatment, but test group and the harmony of matched group in drug combination kind and dosage will be noted.
2.2 efficacy determinations: syndrome integral × 100% before therapeutic index=(before treatment the rear syndrome integral of syndrome integral-treatment)/treatment.Effective: clinical symptom relief, syndrome integral reduces >=30%; Invalid: clinical symptoms is not improved, even increase the weight of, syndrome integral reduces <30%.
3, result
Period in a medicine, treatment group and contrast 2 groups respectively have 1 case to lose, and contrasting 1 group has 2 cases to lose.
Clinical efficacy comparison: treatment group total effective rate 92%, compares between matched group total effective rate 82%, two groups and has significant difference (P<0.05).
Table 11 Clinical efficacy comparison
Wherein, with contrast 1 group and compare, * * P < 0.01; With contrast 2 groups and compare, #P < 0.05
Result shows, the basis-reinforcing eyesight-improving eye drop that extractive composition of the present invention obtains has good curative effect for treatment xerophthalmia, effect is extremely significantly better than former technique basis-reinforcing eyesight-improving granule (P < 0.01), is significantly better than the basis-reinforcing eyesight-improving dropping pill (P < 0.05) of drop pill application.
Dose comparison used by table 12 day
As can be seen from above-mentioned daily dose comparison data, the daily medical material doses of eye drop preparation is far smaller than granule group and drop pill group, and the use amount of granule, drop pill is equivalent to 52 times of eye drop of the present invention.
Research finds, the eye drop eliminating volatile oil not only zest reduces greatly, and curative effect slightly promotes, and greatly reduces use amount simultaneously.
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment 1, a kind of eye drop being used for the treatment of xerophthalmia, supplementary material is composed as follows:
Make 5000ml
Its preparation method is:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 364g, Fructus Chebulae 364g, Corydalis impatiens (Pall.) Fisch. 121g, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 8 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 4 times amount volumes, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5g, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: take 2.5g Borneolum Syntheticum, add 95% ethanol 7.5g and make dissolving, then add the PEG600 of 7.5g, filter for subsequent use; Join in 2500ml water for injection by the extract containing Fel Ursi powder, stirring and dissolving, filter, get above-mentioned Borneolum Syntheticum solution and join in water precipitating thing solution, limit edged stirs, then adds 2000ml water for injection; In solution, add 40g Borax, 10g boric acid and 1.5g benzene Zha Lvte again, be stirred to dissolve, inject water to 5000ml, mixing, filter, to obtain final product.
Embodiment 2, a kind of eye drop being used for the treatment of xerophthalmia, supplementary material is composed as follows:
Make 5000ml
Its preparation method is:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 340g, Fructus Chebulae 340g, Corydalis impatiens (Pall.) Fisch. 110g, extract 2 times at adding 65% ethanol 45 DEG C, first time adds 6 times amount ethanol, extract 1 hour, second time adds 6 times amount ethanol, extract 1 hour, filter, filtrate recycling ethanol, being evaporated to relative density is again 1.20-1.25 (50 DEG C of surveys), add the water of 3 times of concentrated solution weight, get Fel Ursi powder 8g, add suitable quantity of water to dissolve, Fel Ursi powder aqueous solution is joined in alcohol aqueous suspension, stir 10min, Cryoprecipitation 12 hours, filter, filtrate is concentrating under reduced pressure again, spraying dry, obtain,
2) prepare eye drop: take 1.5g Borneolum Syntheticum, add 6g80% ethanol and make dissolving, then add 6gPEG400, filter for subsequent use; Join in 200ml water for injection by the extract containing Fel Ursi powder, stirring and dissolving, filter, get above-mentioned Borneolum Syntheticum solution and join in water precipitating thing solution, limit edged stirs, then adds 4400ml water for injection; In solution, add 40g Borax, 10g boric acid and 1g benzene Zha Lvte again, be stirred to dissolve, inject water to 5000ml, mixing, filter, to obtain final product.
Embodiment 3, a kind of eye drop being used for the treatment of xerophthalmia, supplementary material is composed as follows:
Make 5000ml
Its preparation method is:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 400g, Fructus Chebulae 400g, Corydalis impatiens (Pall.) Fisch. 130g, add 95% ethanol 80 DEG C at extract 4 times, add 10 times amount ethanol at every turn, extract 4 hours, filter, filtrate recycling ethanol, being evaporated to relative density is again 1.20-1.25 (50 DEG C of surveys), adds the water of 5 times of concentrated solution weight, gets Fel Ursi powder 12g, add suitable quantity of water to dissolve, Fel Ursi powder aqueous solution is joined in alcohol aqueous suspension, stirs 30min, Cryoprecipitation 48 hours, filter, filtrate is concentrating under reduced pressure again, spraying dry, to obtain final product;
2) prepare eye drop: take 3.3g Borneolum Syntheticum, add 10g90% ethanol and make dissolving, then add 10gPEG600, filter for subsequent use; Join in 4500ml water for injection by the extract containing Fel Ursi powder, stirring and dissolving, filter, get above-mentioned Borneolum Syntheticum solution and join in water precipitating thing solution, limit edged stirs, then adds 100ml water for injection; In solution, add 40g Borax, 10g boric acid and 2g benzene Zha Xiute again, be stirred to dissolve, inject water to 5000ml, mixing, filter, to obtain final product.
Embodiment 4, a kind of eye drop being used for the treatment of xerophthalmia, supplementary material is composed as follows:
Make 5000ml
Its preparation method is:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 364g, Fructus Chebulae 364g, Corydalis impatiens (Pall.) Fisch. 121g, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 10 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add 4 times of water gagings, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5g, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: take 3.3g Borneolum Syntheticum, add 10g95% ethanol and make dissolving, then add 10gPEG600, filter for subsequent use; Join in 2500ml water for injection by the extract containing Fel Ursi powder, stirring and dissolving, filter, get above-mentioned Borneolum Syntheticum solution and join in water precipitating thing solution, limit edged stirs, then adds 2000ml water for injection; In solution, add 40g Borax, 10g boric acid and 2g benzene Zha Lvte again, be stirred to dissolve, inject water to 5000ml, mixing, filter, to obtain final product.
Claims (8)
1. be used for the treatment of an eye drop for xerophthalmia, be characterised in that, the weight portion of its supplementary material is composed as follows:
Containing extract 130-170 part of Fel Ursi powder
Borneolum Syntheticum 1.5-3.3 part
Antibacterial 1-2 part
Solubilizing agent 6-10 part
Borax 40 parts
Boric acid 10 parts
Volumetric concentration 80-95% ethanol 6-10 part
Water for injection is appropriate
Make 5000 times amount volumes altogether;
Extract wherein containing Fel Ursi powder is prepared from by the following method:
Get Flos Carthami 340-400 part, Fructus Chebulae 340-400 part, Corydalis impatiens (Pall.) Fisch. 110-130 part by weight, add volume ratio 65-95% ethanol to extract 2-4 time in 45-80 DEG C, add medical material weight 6-10 times amount volume at every turn, each extraction time 1-4 hour, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 3-5 times amount volume, obtain alcohol aqueous suspension; Get Fel Ursi powder 8-12 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 10-30 minute, leave standstill 12-48 hour, filter, filtrate reduced in volume, spraying dry, must containing the extract of Fel Ursi powder.
2. eye drop according to claim 1, is characterised in that, the extract containing Fel Ursi powder is prepared from by the following method:
Get 364 parts, Flos Carthami, Fructus Chebulae 364 parts, Corydalis impatiens (Pall.) Fisch. 121 parts by weight, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 8 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 4 times amount volumes, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, must containing the extract of Fel Ursi powder.
3. eye drop according to claim 1 and 2, is characterised in that, the weight portion of its supplementary material is composed as follows:
Containing the extract 146 parts of Fel Ursi powder
Borneolum Syntheticum 2.5 parts
Antibacterial 1.5 parts
Solubilizing agent 7.5 parts
Borax 40 parts
Boric acid 10 parts
Volumetric concentration 80-95% ethanol 7.5 parts
Water for injection is appropriate
Make 5000 times amount volumes altogether.
4. according to the arbitrary described eye drop of claim 1-3, be characterised in that, described antibacterial be selected from benzene Zha Lvte, benzene is pricked in bromine spy one or both; Described solubilizing agent be selected from PEG400, Macrogol 600 one or both.
5. eye drop according to claim 4, is characterised in that, described antibacterial is benzene Zha Lvte, and described solubilizing agent is Macrogol 600.
6., according to the arbitrary described eye drop of claim 1-5, be characterised in that, the volumetric concentration of described ethanol is 95%.
7. the preparation method of eye drop according to claim 1, is characterised in that, step is as follows:
1) preparation is containing the extract of Fel Ursi powder: get Flos Carthami 340-400 part, Fructus Chebulae 340-400 part, Corydalis impatiens (Pall.) Fisch. 110-130 part by weight, add volume ratio 65-95% ethanol to extract 2-4 time in 45-80 DEG C, add medical material weight 6-10 times amount volume at every turn, each extraction time 1-4 hour, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add 3-5 times amount volume water, obtain alcohol aqueous suspension; Get Fel Ursi powder 8-12 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 10-30 minute, leave standstill 12-48 hour, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: get 1.5-3.3 part Borneolum Syntheticum by weight, add 6-10 part volumetric concentration 80-95% ethanol and make dissolving, then add the solubilizing agent of 6-10 part, filter to obtain Borneolum Syntheticum solution for standby; Join in the water for injection of 200-4500 times amount volume by the extract containing Fel Ursi powder of 130-170 weight portion, stirring and dissolving, filters to obtain water precipitating thing solution; Getting above-mentioned Borneolum Syntheticum solution joins in water precipitating thing solution, and limit edged stirs, then adds the water for injection of 100-4400 times amount volume, add 40 parts of Boraxs, 10 parts of boric acid and 1-2 part antibacterial again, be stirred to dissolve, inject water to 5000 times amount volumes, mixing, filters, to obtain final product.
8. the preparation method of eye drop according to claim 7, is characterised in that, step is as follows:
1) preparation is containing the extract of Fel Ursi powder: get 364 parts, Flos Carthami, Fructus Chebulae 364 parts, Corydalis impatiens (Pall.) Fisch. 121 parts by weight, add volume ratio 90% ethanol to extract 2 times in 60 DEG C, first time adds 8 times amount volumes, extract 3 hours, second time adds 8 times amount volumes, extracts 2 hours, filter, be evaporated to 50 DEG C after filtrate recycling ethanol again and survey relative density 1.20-1.25, add the water of 4 times amount volumes, obtain alcohol aqueous suspension; Get Fel Ursi powder 10.5 weight portion, join in aforementioned alcohol aqueous suspension after being dissolved in water, stir 25 minutes, leave standstill 24 hours, filter, filtrate reduced in volume, spraying dry, to obtain final product;
2) prepare eye drop: get 2.5 parts of Borneolum Syntheticums by weight, add 7.5 parts of volume ratio 95% ethanol and make dissolving, then add 7.5 parts of solubilizing agents, filter to obtain Borneolum Syntheticum solution for standby; Join in the water for injection of 2500 times amount volumes by the extract containing Fel Ursi powder of 146 weight portions, stirring and dissolving, filters to obtain water precipitating thing solution; Getting above-mentioned Borneolum Syntheticum solution joins in water precipitating thing solution, and limit edged stirs, then adds the water for injection of 2000 times amount volumes, in solution, add 40 parts of Boraxs, 10 parts of boric acid and 1.5 parts of antibacterial again, be stirred to dissolve, inject water to 5000 times amount volumes, mixing, filters, to obtain final product;
Described times amount volume refers to the corresponding relation of weight and volume, and unit is ml/g or L/kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410165886.5A CN105012404B (en) | 2014-04-23 | 2014-04-23 | It is a kind of to be used to treat eye drops of scheroma and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410165886.5A CN105012404B (en) | 2014-04-23 | 2014-04-23 | It is a kind of to be used to treat eye drops of scheroma and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105012404A true CN105012404A (en) | 2015-11-04 |
| CN105012404B CN105012404B (en) | 2018-02-23 |
Family
ID=54402949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410165886.5A Active CN105012404B (en) | 2014-04-23 | 2014-04-23 | It is a kind of to be used to treat eye drops of scheroma and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105012404B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108904568A (en) * | 2018-08-01 | 2018-11-30 | 青海大学 | A kind of preparation method and eyesight improving liquid of eyesight improving liquid |
| US11058736B2 (en) * | 2018-08-24 | 2021-07-13 | Korea Institute Of Science And Technology | Method of treating dry eye syndrome using pharmaceutical composition having extract of Terminalia chebula or fraction thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709419A (en) * | 2005-06-13 | 2005-12-21 | 北京正大绿洲医药科技有限公司 | Basis-reinforcing eyesight-improving dropping pill for treating eye disease and its preparing method |
| CN103185768A (en) * | 2011-12-31 | 2013-07-03 | 山东阿如拉药物研究开发有限公司 | Quality detection method for traditional Chinese medicine preparation for strengthening foundation and improving eyesight |
-
2014
- 2014-04-23 CN CN201410165886.5A patent/CN105012404B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709419A (en) * | 2005-06-13 | 2005-12-21 | 北京正大绿洲医药科技有限公司 | Basis-reinforcing eyesight-improving dropping pill for treating eye disease and its preparing method |
| CN103185768A (en) * | 2011-12-31 | 2013-07-03 | 山东阿如拉药物研究开发有限公司 | Quality detection method for traditional Chinese medicine preparation for strengthening foundation and improving eyesight |
Non-Patent Citations (3)
| Title |
|---|
| 倪健: "《中药药剂学》", 31 July 2013, 中国医药科技出版社 * |
| 刘天强等: "SS熊胆眼药水刺激性研究", 《亚太传统医药》 * |
| 梁安鹏等: "《药物集成.5，中成药及民族药制剂》", 30 June 2008, 中国医药科技出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108904568A (en) * | 2018-08-01 | 2018-11-30 | 青海大学 | A kind of preparation method and eyesight improving liquid of eyesight improving liquid |
| US11058736B2 (en) * | 2018-08-24 | 2021-07-13 | Korea Institute Of Science And Technology | Method of treating dry eye syndrome using pharmaceutical composition having extract of Terminalia chebula or fraction thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105012404B (en) | 2018-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Holzchuh et al. | Clinical treatment of ocular Demodex folliculorum by systemic ivermectin | |
| CN101843662B (en) | Chinese medicinal composition for preventing and treating asthenopia | |
| CN101716214B (en) | Medical composition containing dandelion extract as well as novel application and preparation method thereof | |
| CN108567910A (en) | The Chinese medicine composition of eye strain is alleviated in a kind of external application | |
| CN102145126B (en) | Pharmaceutical composition for treating xerophthalmia | |
| CN101564375A (en) | Chinese medicinal in situ forming eye gel | |
| CN103040888A (en) | Ophthalmologic external preparation, as well as preparation method and application thereof | |
| CN107898816A (en) | Eye medicinal preparation and its application | |
| CN107951955A (en) | A kind of compound for alleviating asthenopia | |
| CN102362924A (en) | Medicinal composition for treating ophthalmic diseases and preparation method thereof | |
| CN113813315A (en) | Traditional Chinese medicine composition for relieving asthenopia and xerophthalmia, application thereof and prepared eye mask | |
| CN106581446A (en) | Application of herba dendrobii extractives for preparing medicine capable of treating xerophthalmia, and medicine | |
| CN105012404B (en) | It is a kind of to be used to treat eye drops of scheroma and preparation method thereof | |
| CN104095982B (en) | A kind of natural plant extracts compound formulation and its production and use | |
| CN103040986B (en) | Ophthalmic gel for treating uveitis and preparation method of ophthalmic gel | |
| CN100569218C (en) | Benzydalysine eye drop and preparation method thereof | |
| CN104906220A (en) | Traditional Chinese medicine for treating herpes zoster and herpes simplex viral keratitis | |
| CN1899339B (en) | Medicinal composition for treating acute and chronic conjunctivitis for eye and its preparing method | |
| CN100563628C (en) | A kind of Bendalysine eye gel preparation and preparation method thereof | |
| CN100577187C (en) | Chinese medicine preparation for treating eye fatigue and its preparing process | |
| CN102988278A (en) | Bromfenac sodium hydrate eye drops and preparation method thereof | |
| CN1311842C (en) | Medicine for treating chronic conjunctivitis | |
| CN102512362B (en) | Formula and preparation method of compound ciprofloxacin eye drops | |
| CN102078287B (en) | Ophthalmic gel of artificial musk and preparation method thereof | |
| CN108114021A (en) | A kind of pharmaceutical composition for being used to treat virus infected herpes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: No. 322, No. 501-506, Shun Feng Road, Ji'nan high tech Zone (calendar), Shandong Province Applicant after: Shandong Jin He drug development research company limited Address before: No. 322, No. 501-506, Shun Feng Road, Ji'nan high tech Zone (calendar), Shandong Province Applicant before: Shandong ARURA Pharmaceutical Research & Development Co., Ltd. |
|
| CB02 | Change of applicant information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Niu Yulian Inventor after: Zhang Yizhi Inventor after: Li Huaiping Inventor after: Ji Tao Inventor after: Wei Yongyi Inventor after: Peng Kun Inventor before: Zhang Yizhi Inventor before: Li Huaiping Inventor before: Ji Tao Inventor before: Wei Yongyi Inventor before: Peng Kun |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 250101 Shandong Province Jinan Hi-tech Zone Comprehensive Bonded Zone No. 1 North Section of Gangxing No. 3 Road Jinan Yaogu R&D Platform Area No. 3 Floor 8001 Patentee after: Jinhe Tibetan Medicine (Shandong) Health Industry Co.,Ltd. Address before: Room 501-506, 322 Shunfeng Road, high tech Zone, Jinan City, Shandong Province, 250101 Patentee before: SHANDONG JINHE DRUG RESEARCH DEVELOPMENT Co.,Ltd. |
|
| CP03 | Change of name, title or address |