CN109481434A - Eye drops, and the preparation method and application thereof - Google Patents
Eye drops, and the preparation method and application thereof Download PDFInfo
- Publication number
- CN109481434A CN109481434A CN201811550047.XA CN201811550047A CN109481434A CN 109481434 A CN109481434 A CN 109481434A CN 201811550047 A CN201811550047 A CN 201811550047A CN 109481434 A CN109481434 A CN 109481434A
- Authority
- CN
- China
- Prior art keywords
- eye drops
- taurine
- eye
- adjusting agent
- solubilizer
- 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.)
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- 239000003889 eye drop Substances 0.000 title claims abstract description 89
- 229940012356 eye drops Drugs 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 74
- 229960003080 taurine Drugs 0.000 claims abstract description 37
- 229960005149 bendazac Drugs 0.000 claims abstract description 34
- BYFMCKSPFYVMOU-UHFFFAOYSA-N bendazac Chemical compound C12=CC=CC=C2C(OCC(=O)O)=NN1CC1=CC=CC=C1 BYFMCKSPFYVMOU-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003002 pH adjusting agent Substances 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 15
- 230000003204 osmotic effect Effects 0.000 claims abstract description 15
- 208000002177 Cataract Diseases 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 9
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 9
- 229960003943 hypromellose Drugs 0.000 claims description 9
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 4
- 206010015946 Eye irritation Diseases 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 239000008215 water for injection Substances 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000003841 chloride salts Chemical group 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 239000002736 nonionic surfactant Substances 0.000 claims 1
- NFIYTPYOYDDLGO-UHFFFAOYSA-N phosphoric acid;sodium Chemical compound [Na].OP(O)(O)=O NFIYTPYOYDDLGO-UHFFFAOYSA-N 0.000 claims 1
- 230000028327 secretion Effects 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 11
- 230000001225 therapeutic effect Effects 0.000 abstract description 7
- 230000002195 synergetic effect Effects 0.000 abstract description 6
- 206010030113 Oedema Diseases 0.000 abstract description 4
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000000470 constituent Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 210000000695 crystalline len Anatomy 0.000 description 7
- 230000007794 irritation Effects 0.000 description 7
- 230000000857 drug effect Effects 0.000 description 6
- 229920000136 polysorbate Polymers 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 5
- 235000019799 monosodium phosphate Nutrition 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 229960000686 benzalkonium chloride Drugs 0.000 description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical group [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 102000016912 Aldehyde Reductase Human genes 0.000 description 2
- 108010053754 Aldehyde reductase Proteins 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 210000000795 conjunctiva Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001408 fungistatic effect Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- SEGLCEQVOFDUPX-UHFFFAOYSA-N di-(2-ethylhexyl)phosphoric acid Chemical compound CCCCC(CC)COP(O)(=O)OCC(CC)CCCC SEGLCEQVOFDUPX-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
-
- 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
- A61P27/12—Ophthalmic agents for cataracts
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to eye-drops preparations fields, and in particular to a kind of eye drops, and the preparation method and application thereof.It include 0.05-0.1g bendazac lysine, 3-7g taurine, 0.05-0.1g pH adjusting agent, 1.0-3.0g osmotic pressure regulator, 0.05-0.15g solubilizer and 0.1-0.3g tackifier in every 1000 milliliters of eye drops.It is shared by taurine and bendazac lysine; it is synergistic; promote its therapeutic effect to cataract; taurine and bendazac lysine share the side effect that can be substantially reduced eye drops simultaneously; reduce eye secretion after applying drug; probability of happening is substantially reduced phenomena such as redness, oedema simultaneously, promotes the experience sense of patient medication.
Description
Technical field
The present invention relates to eye-drops preparations fields, and in particular to a kind of eye drops, and the preparation method and application thereof.
Background technique
Benzydalysine eye drop is aldose reductase inhibitor, aldose reductase can promote the lenticular glucose of people and
Galactolipin is reduced into the alcohols for being difficult to penetrate into cell membrane, and absorbs cell membrane free surface moisture and enter crystalline lens, keeps crystallin fine
Dimension expansion, changes translucency to form cataract at structure disturbance.Benzydalysine eye drop can enter eye by Local eye drop
Tissue and aqueous humor, and assemble in crystalline lens, effectively inhibit the activity of intraocular aldose reductase, delay cataract development into
Journey achievees the purpose that prevention or treatment cataract.But bendazac lysine has larger irritation to eye, and it is intraocular to easily lead to patient
Red and swollen, secretion increases, and adverse reaction rate increases, so that patient's poor compliance,
Summary of the invention
The purpose of the present invention is to provide a kind of eye drops, which has therapeutic effect well for cataract, together
When can reduce stimulation of the eye drops to eye, reduce patient medication pain, promoted patient compliance medication experience, promoted
The drug effect of drug.
Another object of the present invention is to provide a kind of preparation methods of eye drops, and the technique is simple, quality controllable, can
Eye drops is quickly prepared.
Another object of the present invention is to provide a kind of applications of eye drops, can expand the application range of eye drops.
The present invention solves its technical problem and adopts the following technical solutions to realize:
The present invention proposes a kind of eye drops, includes 0.05-0.1g bendazac lysine, 3- in every 1000 milliliters of eye drops
7g taurine, 0.05-0.1gpH regulator, 1.0-3.0g osmotic pressure regulator, 0.05-0.15g solubilizer and 0.1-0.3g increase
Stick.
The present invention proposes a kind of preparation method of eye drops, comprising the following steps: by bendazac lysine, taurine, pH tune
Section agent, osmotic pressure regulator, solubilizer and tackifier are mixed to form eye drops.
The present invention proposes that a kind of eye drops treats cataract medicine in preparation and reduces the application in irritation eye medicinal.
Eye drops of the present invention, and the preparation method and application thereof beneficial effect be: eye drops passes through taurine and benzyl Dalai
Propylhomoserin shares, synergistic, promotes its therapeutic effect to cataract, while share can be obvious for taurine and bendazac lysine
The side effect of eye drops is reduced, reduces eye secretion after applying drug, while probability of happening obviously drops phenomena such as redness, oedema
It is low, promote the experience sense of patient medication.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
In the description of the present invention, it should be noted that term " first ", " second " etc. are only used for distinguishing description, without
It can be interpreted as indication or suggestion relative importance.
The eye drops of the embodiment of the present invention, preparation method and its application are specifically described below.
A kind of eye drops provided in an embodiment of the present invention, interior every 1000 milliliters of eye drops include that 0.05-0.1g benzyl reaches
Lysine, 3-7g taurine, 0.05-0.1g pH adjusting agent, 1.0-3.0g osmotic pressure regulator, 0.05-0.15g solubilizer and
0.1-0.3g tackifier.It or include bendazac lysine, 5-6g institute described in 0.07-0.09g in every 1000 milliliters of eye drops
State solubilizer described in pH adjusting agent described in taurine, 0.06-0.08g, osmotic pressure regulator, 0.08-0.12g described in 1.5-2g and
Tackifier described in 0.2-0.25g.
Cataract can be alleviated or be treated to Benzydalysine eye drop in the prior art, but its in practical application is treated
Effect is general, and Benzydalysine eye drop is big to Ocular irritation, is easy to cause patient intraocularly red and swollen after dropwise addition, and increases tear
The secretion such as water, and tear is easy the Benzydalysine eye drop containing active constituent going out eyes, then further decreases
The therapeutic effect of Benzydalysine eye drop.The present embodiment passes through the association of taurine and bendazac lysine by addition taurine
Same synergistic effect promotes the therapeutic effect of eye drops, while Papillary can also reduce stimulation of the eye drops to eyes of patients,
The pain of patient medication is reduced, secretion is reduced, avoids secretion to the dilution of active constituent and wash away, is then further promoted
Eye to active constituent absorbs, and promotes drug effect.
It can either further ensure that the two plays well additionally by the ratio of control taurine and bendazac lysine
Synergistic function, meanwhile, it is capable to further decrease the side effect of eye drops.It is gone back by taurine and sharing for bendazac lysine
Fungistatic effect well can be played, no longer needs to additionally add other bacteriostatic agents.
And the type of the auxiliary materials such as pH adjusting agent, osmotic pressure regulator, solubilizer and tackifier is further controlled, it can either protect
The stability and drug effect for demonstrate,proving eye drops, prevent auxiliary material from having an impact to the drug effect of eye drops, while guaranteeing human body in eye drops
Absorb to active constituent.And the dosage of auxiliary material in eye drops is further controlled, it can further guarantee the drug effect of eye drops, drop
Its low side effect.
Further, pH adjusting agent is phosphate；Preferably, sodium dihydrogen phosphate and/or disodium hydrogen phosphate.Using above-mentioned object
Matter guarantees the stability of eye drops as pH adjusting agent, prevent the rotten of eye drops, the pH adjusting agent and osmotic pressure regulator and
Solubilizer shares, and human body can be promoted to active constituent low absorption.
Further, osmotic pressure regulator is chloride, preferably sodium chloride.It can with promote human body to taurine,
It absorbs to bendazac lysine, and eye drops can be further decreased to human body to stimulate.
Further, tackifier are cellulose substances, preferably hypromellose.It can be protected using above-mentioned substance
Demonstrate,prove eye drops stability, settle with preventing active constituent, further protection can only eye drops drug effect.
Further, solubilizer is surfactant, preferably nonionic surface active agent, more preferably Tween 80.
The solubility of drug and the stability of eye drops can further be promoted using above-mentioned solubilizer, promote the curative effect of eye drops, and
Reduce the side effect of eye drops.
Further, further include 0.01-0.03g preservative in 1000mL eye drops, be additionally further added by preservative, Neng Goujin
One step promotes the fungistatic effect of eye drops, extends its shelf-life.And preservative is benzalkonium chloride, uses the reagent for preservative energy
It is enough to sterilize well.
Further, its surplus is water for injection in 1000mL eye drops.
Further, the embodiment of the present invention also provides a kind of preparation method of eye drops, comprising the following steps:
Firstly, according to the dosage of each substance of recipe calculation, after then mixing pH adjusting agent raw material with water for injection
To pH adjusting agent liquid.
Bendazac lysine and solubilizer and appropriately injection water are mixed to get the first mixed liquor, first by bendazac lysine and
Solubilizer carries out mixed dissolution, is able to ascend the dissolution degree of raw material, then promotes active constituent ground content in eye drops.
Taurine and appropriately injection water are subjected to mixed dissolution, guarantee that each material can be uniformly mixed, and guarantees ox
Sulfonic acid can be sufficiently mixed with bendazac lysine, guarantee the synergistic effect of the two.
Suitable injection water is added in reactor, and is warming up to 90-100 DEG C, injection water is heated, each substance is promoted
Solubility, and it is uniform to be conducive to each material mixing.Then successively with tackifier, pH adjusting agent, osmotic pressure regulator, first
Mixed solution, taurine are mixed to get medical fluid.
Then medical fluid is cooled down after persistently stirring 25-40 minutes at 90-100 DEG C, keeps constant temperature stirring more advantageous
Each raw material is uniformly mixed in eye drops.Constant volume is filtered and carried out after cooling, so that each raw material meets regulation.
The present invention proposes that a kind of eye drops treats cataract medicine in preparation and reduces the application in irritation eye medicinal.
Feature and performance of the invention are described in further detail with reference to embodiments.
Embodiment 1
The present embodiment provides a kind of eye drops (1000mL) comprising 0.05g bendazac lysine, 3g taurine, 0.05g
PH adjusting agent, 1.0g sodium chloride, 0.05g Tween 80,0.1g hypromellose, surplus are water.Wherein, pH adjusting agent is
The mixture of sodium dihydrogen phosphate and disodium hydrogen phosphate.
The present embodiment also provides a kind of preparation method of eye drops:
PH adjusting agent solution is obtained to sodium dihydrogen phosphate and disodium hydrogen phosphate to be dissolved in injection water；
Tween 80 and bendazac lysine are dissolved in injection water and obtain the first mixed solution；
Taurine is dissolved in injection water and obtains taurine solution；
Will appropriate injection water be added reactor in be warming up to 90 DEG C, then successively with hypromellose, pH adjusting agent
Solution, osmotic pressure regulator, the first mixed liquor and taurine solution mixing, then keep 90 DEG C, stir 40 minutes, then cold
But, and injection water constant volume is added.
Embodiment 2-6
The eye drops that embodiment 2-6 is provided is identical as the eye drops raw material that embodiment 1 provides, and difference is specific dosage not
Together；The preparation method for the eye drops that embodiment 2-6 is provided and the preparation method for the eye drops that embodiment 1 provides are essentially identical, area
It is not operating condition difference.
Embodiment 2
Eye drops (1000mL) include 0.1g bendazac lysine, 7g taurine, 0.1g pH adjusting agent, 3.0g sodium chloride,
0.15g Tween 80,0.3g hypromellose, surplus are water.Wherein, pH adjusting agent is sodium dihydrogen phosphate.The temperature of heating
Degree is 100 DEG C, and the time persistently stirred is 40 minutes.
Embodiment 3
Eye drops (1000mL) include 0.07g bendazac lysine, 6g taurine, 0.08g pH adjusting agent, 1.5g sodium chloride,
0.12g Tween 80,0.2g hypromellose, surplus are water.Wherein, pH adjusting agent is disodium hydrogen phosphate.The temperature of heating
Degree is 95 DEG C, and the time persistently stirred is 30 minutes.
Embodiment 4
Eye drops (1000mL) include 0.09g bendazac lysine, 5g taurine, 0.06g pH adjusting agent, 2g sodium chloride,
0.08g Tween 80,0.25g hypromellose, surplus are water.Wherein, pH adjusting agent is disodium hydrogen phosphate and di(2-ethylhexyl)phosphate
The mixture of hydrogen sodium.The temperature of heating is 97 DEG C, and the time persistently stirred is 35 minutes.
Embodiment 5
Eye drops (1000mL) includes 0.08g bendazac lysine, 5.5g taurine, 0.07g pH adjusting agent, 1.8g chlorination
Sodium, 0.09g Tween 80,0.22g hypromellose, 0.01g benzalkonium chloride, surplus are water.Wherein, pH adjusting agent is phosphorus
Sour disodium hydrogen.The temperature of heating is 92 DEG C, and the time persistently stirred is 37 minutes.
Embodiment 6
Eye drops (1000mL) includes 0.06g bendazac lysine, 4.5g taurine, 0.09g pH adjusting agent, 1.5g chlorination
Sodium, 0.07g Tween 80,0.15g hypromellose, 0.03g benzalkonium chloride, surplus are water.Wherein, pH adjusting agent is phosphorus
The mixture of sour disodium hydrogen and sodium dihydrogen phosphate.The temperature of heating is 94 DEG C, and the time persistently stirred is 32 minutes.
Comparative example 1: eye drops is prepared according to the preparation method that embodiment 1 provides, difference is that content of taurine is 3g, no
Containing bendazac lysine, remaining constituent content is constant.
Comparative example 2: eye drops is prepared according to the preparation method that embodiment 1 provides, difference is that bendazac lysine content is
0.05g, is free of taurine, remaining constituent content is constant.
Zoopery:
Select Wistar rat, then low dose of (4mg/Kg) sodium selenite of rat skin lower injection, the next day it is primary, continuous 3
It is secondary.Then modeling successfully rat 50, weight 80-120g, half male and half female are taken, and is only grouped according to every group 10 at random,
Wherein one group is control group, and injection water is added dropwise, and remaining 4 groups are successively added dropwise embodiment 1, embodiment 5,1 and of comparative example for experimental group
The eye drops of comparative example 2.Experimental group dripping quantity is 0.5mg/Kg, and same amount of injection water is added dropwise in control group.It is administered daily 2
It is secondary, successive administration 15 days.After 15 days after one 1% atropine mydriasis of groups of animals, is surveyed and recorded crystalline with slit-lamp microscopy
Body muddiness situation, evaluation criterion referring to Song Nianyi, Gao Qiuhua " zinc supplementation to LDH in cataract rat blood and crystalline lens and
The influence of CuZn-SOD " research of ophthalmology, 2005,23 (1): 40-42.Wherein, "-" indicates that crystalline lens is transparent；"+" indicates crystalline
Body core is muddy, but cortex portion is still limpid；" * " indicates that lens nucleus and cortex are muddy.Concrete outcome is referring to table 1.
1 testing result of table
| Crystalline lens | - | + | * | |
| Control group | 20 | 0 | 1 | 19 |
| Embodiment 1 | 20 | 19 | 1 | 0 |
| Embodiment 5 | 20 | 18 | 2 | 0 |
| Comparative example 1 | 20 | 0 | 5 | 15 |
| Comparative example 2 | 20 | 11 | 8 | 1 |
According to table 1, eye drops of the invention generates synergistic effect to crystalline lens by taurine and bendazac lysine
The effect that clarity is restored is preferable, has therapeutic effect well to cataract.
25 eyes are taken to detect undamaged rat (cornea is without muddy, conjunctiva without congested, oedema and secretion), it is random equal
It is divided into 5 groups, every group 5, wherein one group is control group, is added dropwise injection water, remaining 4 groups is successively added dropwise embodiment 1, real for experimental group
Apply the eye drops of example 5, comparative example 1 and comparative example 2；Dripping quantity is 50ul (1-2 drop), continuous dropwise addition 15 days, 3 times a day.
Mice eye secretion is then collected after first day, the 7th day and the 15th day medical fluid for the first time is added dropwise, record is every
Maximal secretory capacity and the amount of every group of average secretion is calculated in group animal, and in secretion maximum and total secretion in every group
The content of bendazac lysine and taurine is detected by high performance liquid chromatography, and testing result is referring to table 2- table 4.
2 first days testing results of table
The 7th day testing result of table 3
The 15th day testing result of table 4
According to table 2- table 4 it is found that bendazac lysine pair can be effectively relieved in the eye drops of the bendazac lysine containing taurine
The irritation of eye avoids its spilling, to increase the absorption in ocular of drug.
It 5 minutes, 30 minutes and direct naked-eye observation or is seen after sixty minutes with magnifying glass before each administration and after administration
Whether angle measurement film, iris, conjunctiva are irritant, and score irritation, and standards of grading are referring to table 5
(CN102670494.B), total mark then is calculated according to standards of grading, and irritation, criterion ginseng is determined according to total mark
6 are shown in Table, is calculated average mark (=total mark/5), evaluation result participates in table 7.
5 evaluation criterion of table
The evaluation of 6 irritation of table
| Score value | 0-3 | 4-8 | 9-12 | 13-16 |
| Evaluation | It is non-stimulated | Slight stimulation | Moderate stimulation | Intensity stimulation |
7 testing result of table
According to table 7 it is found that facilitating the eye drops pair for being used to treat cataract containing bendazac lysine after addition taurine
The irritation of eye is substantially reduced.
In conclusion the eye drops that 1-6 of the embodiment of the present invention is provided shares collaboration by taurine and bendazac lysine and increases
Effect, promotes its therapeutic effect to cataract, while taurine and bendazac lysine share the pair that can be substantially reduced eye drops
Effect reduces eye secretion after applying drug, while probability of happening is substantially reduced phenomena such as redness, oedema, is promoted patient and is used
The experience sense of medicine.
Embodiments described above is a part of the embodiment of the present invention, instead of all the embodiments.Reality of the invention
The detailed description for applying example is not intended to limit the range of claimed invention, but is merely representative of selected implementation of the invention
Example.Based on the embodiments of the present invention, obtained by those of ordinary skill in the art without making creative efforts
Every other embodiment, shall fall within the protection scope of the present invention.
Claims (10)
1. a kind of eye drops, which is characterized in that include 0.05-0.1g bendazac lysine, 3- in every 1000 milliliters of eye drops
7g taurine, 0.05-0.1g pH adjusting agent, 1.0-3.0g osmotic pressure regulator, 0.05-0.15g solubilizer and 0.1-0.3g increase
Stick.
2. eye drops according to claim 1, which is characterized in that include 0.07- in every 1000 milliliters of eye drops
Taurine described in bendazac lysine, 5-6g described in 0.09g, osmotic pressure tune described in pH adjusting agent, 1.5-2g described in 0.06-0.08g
Save tackifier described in solubilizer described in agent, 0.08-0.12g and 0.2-0.25g.
3. eye drops according to claim 1 or 2, which is characterized in that the pH adjusting agent is phosphate；Preferably phosphoric acid
Sodium dihydrogen and/or disodium hydrogen phosphate.
4. eye drops according to claim 1 or 2, which is characterized in that the osmotic pressure regulator is chloride, preferably
Sodium chloride.
5. eye drops according to claim 1 or 2, which is characterized in that the tackifier are cellulose substances, preferably
Hypromellose.
6. eye drops according to claim 1 or 2, which is characterized in that the solubilizer is surfactant, preferably non-
Ionic surfactant, more preferably Tween 80.
7. a kind of preparation method of eye drops described in claim 1, which comprises the following steps: by benzyl Dalai's ammonia
Acid, taurine, pH adjusting agent, osmotic pressure regulator, solubilizer and tackifier are mixed to form eye drops.
8. preparation method according to claim 7, which is characterized in that the eye drops is that water for injection is warming up to 90-
After successively being mixed again with tackifier, pH adjusting agent, osmotic pressure regulator, bendazac lysine, solubilizer and taurine after 100 DEG C
The medical fluid arrived.
9. a kind of application of eye drops described in claim 1 in preparation treatment cataract medicine.
10. a kind of eye drops described in claim 1 reduces the application in irritation eye medicinal in preparation.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4451477A (en) * | 1981-11-27 | 1984-05-29 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Bendazac treatment of cataract |
| CN101564374A (en) * | 2008-04-25 | 2009-10-28 | 北京和润创新医药科技发展有限公司 | Medicinal in situ forming eye gel |
| CN101822677A (en) * | 2009-03-03 | 2010-09-08 | 吴文耀 | Eye drops for cataracts |
| CN103690558A (en) * | 2013-11-26 | 2014-04-02 | 安徽三超药业有限公司 | Eye drop for treating cataract and preparation method thereof |
| CN105687129A (en) * | 2016-03-11 | 2016-06-22 | 广东伊茗药业有限公司 | BDZL (bendazac lysine) eye drops |
| CN105884715A (en) * | 2016-04-23 | 2016-08-24 | 陈斌 | Bendazac lysine pharmaceutical composition and medical application thereof |
| CN105935443A (en) * | 2016-01-08 | 2016-09-14 | 新昌县大成生物科技有限公司 | Pharmaceutical composition for treating diabetic cataract |
-
2018
- 2018-12-18 CN CN201811550047.XA patent/CN109481434B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4451477A (en) * | 1981-11-27 | 1984-05-29 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Bendazac treatment of cataract |
| CN101564374A (en) * | 2008-04-25 | 2009-10-28 | 北京和润创新医药科技发展有限公司 | Medicinal in situ forming eye gel |
| CN101822677A (en) * | 2009-03-03 | 2010-09-08 | 吴文耀 | Eye drops for cataracts |
| CN103690558A (en) * | 2013-11-26 | 2014-04-02 | 安徽三超药业有限公司 | Eye drop for treating cataract and preparation method thereof |
| CN105935443A (en) * | 2016-01-08 | 2016-09-14 | 新昌县大成生物科技有限公司 | Pharmaceutical composition for treating diabetic cataract |
| CN105687129A (en) * | 2016-03-11 | 2016-06-22 | 广东伊茗药业有限公司 | BDZL (bendazac lysine) eye drops |
| CN105884715A (en) * | 2016-04-23 | 2016-08-24 | 陈斌 | Bendazac lysine pharmaceutical composition and medical application thereof |
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