CN108542883A - A kind of spray that eye is applied outside - Google Patents
A kind of spray that eye is applied outside Download PDFInfo
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- CN108542883A CN108542883A CN201810390025.5A CN201810390025A CN108542883A CN 108542883 A CN108542883 A CN 108542883A CN 201810390025 A CN201810390025 A CN 201810390025A CN 108542883 A CN108542883 A CN 108542883A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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Abstract
The present invention provides and applies spray outside a kind of eye containing phosphatide and trehalose, and wherein content of phospholipid is 1 100mg/ml, and content of trehalose is 1 100mg/ml；Preferably, content of phospholipid is 1 20mg/ml, and content of trehalose is 1 50mg/ml；Further preferably, content of phospholipid is 5 15mg/ml, and content of trehalose is 10 30mg/ml.Spray is applied outside eye provided by the invention, can not only be penetrated eye part skin barrier, safely and effectively be treated xerophthalmia, and can extend the time of action, improve the comfort level of patient.Also, spray is applied outside the eye of the present invention as the carrier with pharmacology or beautifying active substance, the permeable membrane uptake of active material can be improved, improve bioavilability, while irritation is not generated to eye.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, and in particular to a kind of spray that eye is applied outside.
Background technology
Xerophthalmia is a kind of common ophthalmology disease, is to cause lacrimal secretion to reduce or evaporate too strong, tear by many reasons
Membrane stability reduces, and then leads to the general name for one group of disease that ocular surface injury is characterized.The common sympton of xerophthalmia is eye part
Stimulation, photophobia, pain, eye-blurred, fatiguability etc..If xerophthalmia cannot be treated effectively, cornea, conjunctiva may be formed
Keratinization, ulcer, so as to cause eyesight degradation.As video display terminal such as computer, TV and mobile phone etc. are in people
Extensive infiltration and contact lens in life are widely used, since frequency of twinkling for a long time reduces, the exposure of ocular tissue
Increase etc. causes xerophthalmia crowd more and more.It is mainly at present artificial tears for the treatment of xerophthalmia and various types of
Eyedrops.No matter artificial tears or eyedrops are required for directly instilling intraocular when in use, and the compliance of patient is poor.
Patent CN1456167A provides a kind of artificial tears containing phosphatide, and patent CN1634123A provides one kind and contains
There are the ophthalmic drug delivery system of phosphatide and sodium hyaluronate, patent CN1651090A to provide a kind of eye containing trehalose and Hyaluronic Acid
Portion's medication transmission system.The above-mentioned ophthalmic remedy mentioned in the prior art is that the direct intraocular that instills uses, for the patient
Compliance is poor.It is domestic at present to only have the preparation for instilling intraocular and using for xerophthalmia.
In order to improve the compliance of patient, Britain Reckitt Benckiser have listed a company a kind of ophthalmically acceptable spraying, commodity
Entitled Optrex, main component include soybean lecithin, VitAVitE, which can be by way of applying outside eye
Alleviate xerophthalmia.But due to the barrier action of skin, the use feeling of patient shorter for the alleviation duration of xerophthalmia
By bad.
Spray belongs to the higher dosage form of safety of current skin or mucosal drug delivery, using also more convenient.But it sprays
Mist agent mainly has there is also some disadvantages：1) due to the barrier action of skin, spray is only applicable to that dosage is small, pharmacological action
Strong drug；2) to skin irritant and anaphylaxis；3) metabolism of skin is acted on storage cavern.Skin and mucous layer are human bodies
To a kind of barrier of drug absorption, amphipathic poor or big molecular weight drug is difficult to enter deep layer through skin and mucous membrane tissue
Tissue and blood circulation play therapeutic effect.Drug is promoted to penetrate skin at present, the method for mucous membrane relies primarily on chemical absorbing rush
Increase the absorption of drug into agent.Although these chemical promoters can improve drug penetrance, most to chemically assist in
Agent can damage or stimulate to skin, mucous membrane.
In order to overcome the deficiencies of existing technologies, it is desirable to provide a kind of spray that eye is applied outside can not only penetrate eye
Skin barrier safely and effectively treats xerophthalmia, and can extend the time of action, improves the comfort level of patient.It is unexpected
, spray is applied as the carrier with pharmacology or beautifying active substance outside eye of the invention, can improve active material
Permeable membrane uptake, improve bioavilability, while irritation do not generated to eye.
Invention content
The present invention provides a kind of spray that eye is applied outside, can penetrate skin barrier and treat xerophthalmia, can obviously prolong
Long onset time substantially increases the level of comfort of user, and can be as the load with pharmacology or beautifying active substance
Body promotes the absorption of active material, improves its bioavilability.
Technical scheme is as follows：
Spray is applied outside a kind of eye of present invention offer, including phosphatide and trehalose.
It is applied in spray outside above-mentioned eye, also includes conventional eye-drops preparations auxiliary material and purified water.
It is applied in spray outside above-mentioned eye, content of phospholipid 1-100mg/ml, content of trehalose 1-100mg/ml.
It is applied in spray outside above-mentioned eye, content of phospholipid 1-20mg/ml, content of trehalose 1-50mg/ml.
It is applied in spray outside above-mentioned eye, content of phospholipid 5-15mg/ml, content of trehalose 10-30mg/ml.
It is applied in spray outside above-mentioned eye, also includes volatile solvent, selected from ethyl alcohol, volatile silicone oils.
It is applied in spray outside above-mentioned eye, also includes preservative, chlorine peace, Phenoxyethanol, oxybenzene are pricked selected from benzalkonium bromide, benzene
Methyl esters, ethyl hydroxy benzoate, butyl hydroxybenzoate, Nipasol, Phenoxyethanol, Butylated Hydroxytoluene, sodium benzoate, potassium sorbate, benzoic acid, chlorine
The sweet ether of benzene, EDTA.
It is applied in spray outside above-mentioned eye, also includes moisturizer, selected from serine, Sodium Hyaluronate, propylene glycol, fourth two
Alcohol, glycerine, dipropylene glycol, acetylation Sodium Hyaluronate, carambola leaf extract, 1,2- pentanediols, panthenol.
It is applied in spray outside above-mentioned eye, also includes antioxidant, selected from vitamin E adenosine, retinol, tocopheryl acetate
Ester, tocopheryl nicotinate, Matrixyl -4, glutathione, aspartic acid.
It applies in spray outside above-mentioned eye, also includes pH adjusting agent, it is slow to, carbonic acid to, borate buffer selected from phosphoric acid buffer
Punching to, hydrochloric acid, sodium hydroxide, sodium citrate, potassium hydroxide, tromethamine.
It is applied in spray outside above-mentioned eye, also includes isotonic regulator, selected from sodium chloride, mannitol, glucose etc..
It is applied in spray outside above-mentioned eye, also includes natural extracts, extracted selected from ginkgo biloba extract, banaba
Object, ginseng root extract, retinyl acetate, Rosmarinus officinalis extract, safflower extract, Portugal leaf extract, Abelmoschus esculentus fruit
Extract, oriental cherry leaf extract, Rosa roxburghii Tratt berry extract, houttuynia extract, Wild soybean seed extract, Fructus Hordei Vulgaris extract, wheat
Germ extracts, yeast extract, radix scutellariae root extract, chicken mulberry root extract, lactobacillus fermentation product, algae extract, Fu
Siberian cocklebur sclerotium extract, Echinacea angustifolia extract, Roman chamomile caul-fat, it is phytosphingosine, Japanese birch bark/leaf extract, big
Any of several broadleaf plants berry extract, oat extract, silk tree bark extract, lemon thyme flower/leaf extract.
The present invention provides the preparation method that spray is applied outside a kind of above-mentioned eye, comprises the steps of：
(1) trehalose is added in purified water, high speed shear；
(2) phosphatide is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Spray is applied outside above-mentioned eye to be used as carrier that pharmacological activity or cosmetic active agent is added.
Trehalose of the invention signified refers to the trehalose in any source, including animal vegetable tissue extraction is isolated, is micro-
What biofermentation or genetic engineering were prepared etc..
Signified phosphatide of the invention refers to the phosphatide in any source, including the phosphatide extracted in yolk or soybean, and with
The phosphatide that synthesis or semisynthesis obtain, or a combination thereof.
Specific implementation mode
Comparative example 1
Preparation method：
(1) Sodium Hyaluronate, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Comparative example 2
Preparation method：
(1) trehalose, Sodium Hyaluronate, sodium chloride are added in purified water, are stirred evenly；
(2) it filters, it is filling.
Comparative example 3
Preparation method：
(1) chloramphenicol, Sodium Hyaluronate, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Comparative example 4
Preparation method：
(1) chloramphenicol, trehalose, Sodium Hyaluronate, sodium chloride are added in purified water, are stirred evenly；(2) it filters, fills
Dress.
Comparative example 5
The ophthalmically acceptable sprayings of Optrex include soybean lecithin 10mg, VITAMIN A PALMITATE 0.25mg, vitamin per 1ml
E0.02mg, Phenoxyethanol 5mg, ethyl alcohol 8mg, sodium chloride 8mg, remaining is purified water.
Embodiment 1
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 2
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 3
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 4
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 5
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 6
Preparation method：
(1) trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 7
Preparation method：
(1) chloramphenicol, trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 8
Preparation method：
(1) chloramphenicol, trehalose, sodium chloride are added in purified water, high speed shear；
(2) egg yolk lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
Embodiment 9
Preparation method：
(1) trehalose, sodium chloride, ethyl alcohol, Phenoxyethanol are added in purified water, high speed shear；
(2) soybean lecithin is added while step (1) high speed shear；
(3) it homogenizes mixture is high-pressure homogeneous obtained by step (2)；
(4) it filters, it is filling.
1 rabbit xerophthalmia model testing experiment of test case
Experimental animal and material healthy rabbits 72, weight 2.5-3.0kg, age 4-5 month.Surgical removal rabbit right eye tear
After gland, Harder glands and instant embrane, is smeared away from bulbar conjunctiva other than corneal limbus 3mm with 50% trichloroacetic acid, rabbit dry eye model, art is made
Start to observe within the 3rd week afterwards.72 rabbit are randomly divided into 9 groups, every group 8.
Administration：One group is control group, gives the blank spray containing only sodium chloride and purified water, remaining eight groups of experiment component
It does not give and applies spray outside the eye of comparative example 1-2, embodiment 1-6.Every rabbit right eye is given 3 times daily, and two sprays, is used in conjunction every time
10 days, check within every two days that 1 right eye angle conjunctiva Schirmer I tests wet length and Rose bengal stain situation, after treatment 10 days
Data evaluation curative effect.
As a result shown in following Tables 1 and 2：
1 different times Schirmer I of table tests wet long relatively
The average tiger of 2 different times angle conjunctiva of table it is red points compare
According to the comparison of embodiment 1 and embodiment 2 and comparative example 1-2 it can be found that phosphatide provided by the invention and seaweed
Sugar combination when eye external spraying is applied effect be far superior to comparative example 1 (phosphatide+Sodium Hyaluronate), comparative example 2 (trehalose+
Sodium Hyaluronate).
According to above-mentioned experimental data it can be found that the eye prepared by 1-6 of the embodiment of the present invention applies spraying for rabbit outside
Xerophthalmia model has good therapeutic effect, the effect of embodiment 3 and embodiment 4 more excellent.
2 permeable membrane aptitude tests of test case are tested
Application spraying outside the eye containing chloramphenicol obtained by embodiment 7-8 and comparative example 3-4 is measured using chicken element cyst membrane
Agent penetrates the ability of biomembrane.
The processing of chicken element cyst membrane：New freshly-slaughtered poultry element capsule is taken, is cleaned, fat deposit is removed, is soaked in spare in physiological saline.
Through biofilm experiments：Using Transdermal diffusion cell, chicken element cyst membrane is taken to be cut into suitable size, be fixed on supply chamber with
Between receiving chamber, saline injection makes probe tube liquid level be slightly above film in receiving chamber, records the liquid measure of addition.Open magnetic force
Blender and constant temperature oil bath keep constant speed stirring, and 37 DEG C of constant temperature, 200 μ L spray solutions of spray are in the chicken element cyst membrane face of supply chamber
On, in 5min, 10min, 30min draws receiving chamber solution 1ml from sample tap and is measured, and supplements fresh life in receiving chamber
Brine 1ml is managed, acquired sample will be measured three times and use Syrups by HPLC drug transmitance.Performance liquid chromatographic column：With
Octadecylsilane chemically bonded silica is filler；Mobile phase A is that 0.01mol/L sodium heptanesulfonate buffer solutions (take biphosphate
Potassium 6.8g dissolves and is diluted to 1000ml with 0.01mol/L heptanesulfonic acid ammonium salt solutions, then adds triethylamine 5ml, and mixing uses phosphoric acid
PH value is adjusted to 2.5), Mobile phase B is methanol；Detection wavelength is 277nm, and according to the form below carries out linear gradient elution.Sampling volume：
10μl。
Test result is as shown in table 3 below：
3 permeable membrane aptitude tests result of table
According to the above results it can be found that compared with comparative example 4-5, the chlorine prepared by the embodiment of the present invention 7 and embodiment 8
Mycin eye external spraying agent is significantly relatively strong through biomembrane ability, and transmitance is more than 75% in 10min, contribute to drug rapidly into
Enter eye and plays curative effect.
3 bioavailability study of test case
Use the eye external spraying agent containing chloramphenicol of comparative example 3-4 and embodiment 7-8, every time two spray.With reference to hairs such as Nie's achievements
The document of table《HPLC methods measure mass concentration of the chloramphenicol ophthalmic solution in rabbit aqueous humor》In detection method, investigate it and be in
Bioavilability in rabbit aqueous humor, as a result see the table below 4.
Pharmacokinetic parameter in 4 rabbit aqueous humor of table
| Group | Cmax(μg/ml) | AUC0-180(min·μg/ml) |
| Comparative example 3 | 0.13 | 10.42 |
| Comparative example 4 | 0.15 | 11.24 |
| Embodiment 7 | 0.29 | 22.24 |
| Embodiment 8 | 0.32 | 24.35 |
According to the above results it can be found that the eye external spraying agent containing chloramphenicol prepared by the present invention, has higher biology
Availability.
The action perdurabgility research of test case 4
Experimental animal and material healthy rabbits 18, weight 2.5-3.0kg, age 4-5 month.Surgical removal rabbit right eye tear
After gland, Harder glands and instant embrane, is smeared away from bulbar conjunctiva other than corneal limbus 3mm with 50% trichloroacetic acid, rabbit dry eye model, art is made
Start to observe within the 3rd week afterwards.18 rabbit are randomly divided into 3 groups, every group 6.
Administration：One group is control group, gives the blank spray containing only sodium chloride and purified water, remaining two groups of experiment component
Comparative example 5, the spray of embodiment 9 are not given.After every rabbit right eye gives two sprays, right eye is checked in 0.5h, 1h, 2h, 3h, 4h
Cornea Schirmer I tests wet length (data that every rabbit measures before administration are 0h data), and log see the table below 5.
Table 5
According to listing test result it can be found that the ophthalmically acceptable spraying of the embodiment of the present invention 9 can hold the alleviation of xerophthalmia
Continue to 4h, and the ophthalmically acceptable spraying of comparative example 5 is only capable of the alleviation of xerophthalmia to continue 2h.
Embodiment 10
Embodiment 11
Using spray is applied outside the eye prepared by embodiment 10-11, xerophthalmia can be effectively treated, and pharmacology is being added
Or permeability and bioavilability can be improved when beautifying active substance.
The preferred embodiment of the present invention is described in detail in the above.But the present invention is not limited to above-mentioned embodiment party
Detail in formula can carry out a variety of simple changes to technical scheme of the present invention within the scope of the technical concept of the present invention
Type, these simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case of shield, it can be combined in any manner.In order to avoid unnecessary repetition, the present invention is to various possible groups
Conjunction mode no longer separately illustrates.
In addition, various embodiments of the present invention can be combined randomly, without departing from this hair
Bright thought, it should also be regarded as the disclosure of the present invention.
Claims (10)
1. applying spray outside a kind of eye, which is characterized in that include phosphatide and trehalose.
2. applying spray outside eye according to claim 1, which is characterized in that also include conventional eye-drops preparations auxiliary material and pure
Change water.
3. applying spray outside eye according to claim 1, which is characterized in that the content of phospholipid is 1-100mg/
Ml, content of trehalose 1-100mg/ml.
4. applying spray outside eye according to claim 3, which is characterized in that the content of phospholipid is 1-20mg/ml,
Content of trehalose is 1-50mg/ml.
5. applying spray outside eye according to claim 4, which is characterized in that the content of phospholipid is 5-15mg/ml,
Content of trehalose is 10-30mg/ml.
6. applying spray outside eye according to claim 1, which is characterized in that also include preservative, selected from benzalkonium bromide,
Benzene pricks chlorine peace, Phenoxyethanol, methyl hydroxybenzoate, ethyl hydroxy benzoate, butyl hydroxybenzoate, Nipasol, Phenoxyethanol, Butylated Hydroxytoluene, benzene first
Sour sodium, potassium sorbate, benzoic acid, Chlorphenesin, EDTA.
7. applying spray outside eye according to claim 1, which is characterized in that also include antioxidant, selected from vitamin E,
Adenosine, retinol, tocopherol acetate, tocopheryl nicotinate, Matrixyl -4, glutathione, aspartic acid.
8. applying spray outside eye according to claim 1, which is characterized in that also include pH adjusting agent, it is slow selected from phosphoric acid
Punching to, borate buffer to, carbonic acid buffering to, hydrochloric acid, sodium hydroxide, sodium citrate, potassium hydroxide, tromethamine.
9. according to the preparation method for applying spray outside any eyes of claim 1-8, comprise the steps of：
（1）Trehalose is added in purified water, high speed shear；
（2）In step（1）Phosphatide is added while high speed shear；
（3）By step（2）Gained mixture is high-pressure homogeneous to be homogenized；
（4）Filtering, it is filling.
10. applying spray outside the eye according to claim 1-8, which is characterized in that can using spray outside the eye
Pharmacological activity or cosmetic active agent is added as carrier.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810390025.5A CN108542883A (en) | 2018-04-26 | 2018-04-26 | A kind of spray that eye is applied outside |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810390025.5A CN108542883A (en) | 2018-04-26 | 2018-04-26 | A kind of spray that eye is applied outside |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111544468A (en) * | 2020-06-24 | 2020-08-18 | 福州华为医药技术开发有限公司 | Eye washing liquid for eye care |
| CN114096165A (en) * | 2020-04-10 | 2022-02-25 | 上海利统生化制品有限公司 | Edible composition for relieving visual fatigue |
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| CN1456167A (en) * | 2003-03-31 | 2003-11-19 | 凌沛学 | Artificial tear containing phosphatide and preparing method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114096165A (en) * | 2020-04-10 | 2022-02-25 | 上海利统生化制品有限公司 | Edible composition for relieving visual fatigue |
| CN114096165B (en) * | 2020-04-10 | 2023-09-19 | 上海利统生化制品有限公司 | Edible composition for relieving asthenopia |
| CN111544468A (en) * | 2020-06-24 | 2020-08-18 | 福州华为医药技术开发有限公司 | Eye washing liquid for eye care |
| CN111544468B (en) * | 2020-06-24 | 2021-10-08 | 福州华为医药技术开发有限公司 | Eye washing liquid for eye care |
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Application publication date: 20180918 |