CN101822677A - Eye drops for cataracts - Google Patents
Eye drops for cataracts Download PDFInfo
- Publication number
- CN101822677A CN101822677A CN200910126350A CN200910126350A CN101822677A CN 101822677 A CN101822677 A CN 101822677A CN 200910126350 A CN200910126350 A CN 200910126350A CN 200910126350 A CN200910126350 A CN 200910126350A CN 101822677 A CN101822677 A CN 101822677A
- Authority
- CN
- China
- Prior art keywords
- solvent
- sodium
- eye drop
- solid
- bernetine
- 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
- 239000003889 eye drop Substances 0.000 title claims abstract description 47
- 229940012356 eye drops Drugs 0.000 title claims abstract 5
- 208000002177 Cataract Diseases 0.000 title abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 75
- 239000003814 drug Substances 0.000 claims abstract description 43
- 229940079593 drug Drugs 0.000 claims abstract description 39
- 239000000243 solution Substances 0.000 claims abstract description 18
- 239000006185 dispersion Substances 0.000 claims abstract description 14
- 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 claims description 64
- 229910052708 sodium Inorganic materials 0.000 claims description 64
- 239000011734 sodium Substances 0.000 claims description 64
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 239000008215 water for injection Substances 0.000 claims description 26
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 20
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 20
- 239000004327 boric acid Substances 0.000 claims description 20
- 239000002671 adjuvant Substances 0.000 claims description 16
- 229960003080 taurine Drugs 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 12
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 12
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 10
- 230000000996 additive effect Effects 0.000 claims description 10
- 239000001103 potassium chloride Substances 0.000 claims description 10
- 235000011164 potassium chloride Nutrition 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 8
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 8
- 229910021538 borax Inorganic materials 0.000 claims description 8
- 239000004328 sodium tetraborate Substances 0.000 claims description 8
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 8
- 229960004926 chlorobutanol Drugs 0.000 claims description 6
- 230000002421 anti-septic effect Effects 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 5
- 230000003078 antioxidant effect Effects 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229960003943 hypromellose Drugs 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 4
- 230000003204 osmotic effect Effects 0.000 claims description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 4
- 229960003415 propylparaben Drugs 0.000 claims description 4
- 235000010338 boric acid Nutrition 0.000 claims description 3
- 238000004806 packaging method and process Methods 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 claims description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- RVKOHSCTEHZRRT-SECBINFHSA-N (2r)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C[C@@H](N)CC2=C1C=CC=C2OC RVKOHSCTEHZRRT-SECBINFHSA-N 0.000 abstract description 9
- 239000007787 solid Substances 0.000 abstract description 9
- 239000004480 active ingredient Substances 0.000 abstract 1
- 239000002243 precursor Substances 0.000 description 29
- 239000008187 granular material Substances 0.000 description 18
- 238000002156 mixing Methods 0.000 description 14
- 238000012856 packing Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 229960000935 dehydrated alcohol Drugs 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000001954 sterilising effect Effects 0.000 description 9
- 238000004659 sterilization and disinfection Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229920003023 plastic Polymers 0.000 description 7
- 239000004033 plastic Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 210000000695 crystalline len Anatomy 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 150000004053 quinones Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 201000004569 Blindness Diseases 0.000 description 2
- 206010007749 Cataract diabetic Diseases 0.000 description 2
- 201000007025 diabetic cataract Diseases 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 201000008525 senile cataract Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 206010036346 Posterior capsule opacification Diseases 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to eye drops for cataracts, which comprise a solid drug packaged independently and a solvent used for dissolving or dispersing the solid drug. The solid drug contains active ingredients and pharmaceutically acceptable assistants, wherein the pH value of solution or dispersion obtained by dissolving or dispersing 0.045-0.060mg of solid drug anhydrous pirenoxine sodium in per milliliter of solvent is more than 4 and less than 4.5. Since the pH value of the solution or dispersion obtained by dissolving or dispersing 0.045-0.060mg of solid drug anhydrous pirenoxine sodium in per milliliter of solvent is more than 4 and less than 4.5, the invention significantly improves the stability of the eye drops,, and the content of the eye drops after being kept for 20 days at the room temperature is above 90 percent, thereby prolonging the effective duration after first use.
Description
Technical field
The present invention relates to a kind of cataractous eye drop that is used for.
Background technology
Cataract is the primary diseases causing blindness of China, and it accounts for the diseases causing blindness component ratio and has surpassed 40%.
Studies show that one of reason that cataract forms is because the interior soluble protein of crystalline lens is subjected to the quinones substance effect, becomes due to the insoluble protein gradually.Quinones substance system is by critical function aminoacid in the body--the abnormal metabolism of-tryptophan is formed.This kind quinones substance can be by the Bernetine Sodium competitive inhibition to the effect of crystalline lens soluble protein.In addition, Bernetine Sodium also can resist radical pair crystalline lens infringement and the cataract that causes.Therefore, Bernetine Sodium has certain inhibition effect to cataractous development.Zoopery shows, Bernetine Sodium can reduce the incidence rate of posterior capsule opacification after the ECCE.The Bernetine Sodium eye drop is mainly treated initial stage senile cataract, slight diabetic cataract or complicated cataract etc. clinically.
Because Bernetine Sodium is unstable in aqueous solution, easily degraded, so, this kind of having gone on the market is both at home and abroad all taked the separately mode of packing at present, be about to Bernetine Sodium and add that adjuvant makes tablet or granule, be equipped with aseptic dedicated solvent again, before using tablet dropped in the dedicated solvent, re-use after waiting medicine to dissolve fully.Its useful life is 20 days or 35 days, yet, there is not both at home and abroad Bernetine Sodium eye drop that document shows this kind packaged form stability after Bernetine Sodium sheet or granule are dissolved in dedicated solvent at present.
The Bernetine Sodium eye drop of two the 4th regulations of China's medicine ministry standard is only measured the content of Bernetine Sodium tablet, and the content that tablet is dissolved in behind the dedicated solvent is not controlled.And in fact,, just can play the effect of treatment initial stage senile cataract, slight diabetic cataract or complicated cataract etc. because Bernetine Sodium has only the content of Bernetine Sodium to reach finite concentration after being dissolved in dedicated solvent.
The present inventor has carried out following test: the method on the Bernetine Sodium eye drop by specification that will buy from the market is dissolved in dedicated solvent separately with tablet, measure content with high-efficient liquid phase technique, as 0 day content, again sample is placed 25 ℃ of constant temperature ovens, measure its content in the 5th day reuse high-efficient liquid phase technique, the result shows, sells the Bernetine Sodium eye drop on the market and places 5 days its content descend and just all surpassed 10% under 25 ℃ of conditions.If press the common content span of control 90～110% of medicine, by 100% production that feeds intake, then its effect duration is no more than 5 days.Do not reach 20 days of defined in the description at all.
Summary of the invention
The objective of the invention is provides a kind of Bernetine Sodium eye drop that can prolong the effect duration after using first in order to overcome the short shortcoming of effect duration after existing Bernetine Sodium eye drop uses first.
The present inventor finds, when existing Bernetine Sodium eye drop used, to contain the pH value of the eye drop that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg be more than 4.5 for dissolving or disperse in every milliliter of dedicated solvent.Simultaneously, the present inventor also is surprised to find that, the pH value that dissolving or disperse contains the eye drop that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg in every milliliter of dedicated solvent is for greater than 4 to less than 4.5 o'clock, eye drop stable very good.
Based on above discovery, the invention provides a kind of cataractous eye drop that is used for, wherein, this eye drop comprises the solid-state drug of independent packaging and is used to dissolve or disperse the solvent of this solid-state drug, described solid-state drug contains active component and pharmacy acceptable auxiliary, described active component is a Bernetine Sodium, wherein, in every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg or the pH value of dispersion liquid for greater than 4 to less than 4.5.
According to eye drop provided by the invention, in every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg or the pH value of dispersion liquid for greater than 4 to less than 4.5, significantly improved the stability of eye drop, the content that room temperature is placed after 20 days down is more than 90%, thereby has prolonged the effect duration after using first.
The specific embodiment
Provided by the inventionly be used for cataractous eye drop and comprise the solid-state drug of independent packaging and be used to dissolve or disperse the solvent of this solid-state drug, described solid-state drug contains active component and pharmacy acceptable auxiliary, described active component is a Bernetine Sodium, wherein, in every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg or the pH value of dispersion liquid for greater than 4 to less than 4.5.
The form of described solid-state drug can be various solid dosages, is preferably tablet, granule.
Described pharmacy acceptable auxiliary can be used to prepare the adjuvant of the solid-state drug of eye drop for routine various.Under the preferable case, described adjuvant is at least a in taurine, boric acid and the Borax.The weight ratio of active component and adjuvant can change within a large range, can select suitable ratio according to actual needs, and for example, the weight ratio of active component and adjuvant can be 1: 60-180 is preferably 1: 90-120.
Described solid-state drug can adopt conventional the whole bag of tricks to make, for example, adjuvant can be mixed with active component, and the adding binding agent, granulation, drying is sieved, tabletting or make granule.
In a preferred embodiment of the invention, every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.053mg or the pH value of dispersion liquid for greater than 4 to less than 4.5.
According to another preferred implementation of the present invention, dissolving or disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.053mg or the pH value of dispersion liquid is 4.05-4.45 in every milliliter of solvent.According to this preferred implementation, can further improve the stability of eye drop.
Described solvent can be being specifically designed to dissolving or disperseing the solvent of this solid-state drug of routine, if the pH value of solvent can make dissolving in every milliliter of solvent or disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.053mg or the pH value of dispersion liquid within the scope of the invention.
For example, described solvent can contain water for injection, pH regulator agent and additive.Described additive can be the additive that is used for described solvent of routine, and those skilled in the art can select the kind and the content of suitable additive as required.For example, described additive can be selected from least a in antiseptic, surfactant, viscosity modifier and the antioxidant, and content of additive can be the 10-26 grams per liter, is preferably the 20-22 grams per liter.The solution that the content of pH regulator agent obtains after making the solid-state drug dissolving or being distributed in the solvent or the pH of dispersion liquid are within the scope of the invention.
The preparation method of described solvent can for example, join additive and pH regulator agent in the water for injection according to the preparation method of routine, and heat sterilization gets final product after the dissolving, and different is to determine the consumption of pH regulator agent as follows:
Additive is joined in the water for injection, heat sterilization after the dissolving, note is solvent precursor A.To contain the solid-state drug dissolving of the anhydrous Bernetine Sodium of 0.675-0.9mg (preferred 0.8mg) or be distributed among the 15ml solvent precursor A, use the pH regulator agent that the solution that obtains or the pH value of dispersion liquid are adjusted the consumption of pH regulator agent when record transfers to pH value in the scope of the present invention.The pH regulator agent of record amount is joined among the 1ml solvent precursor A, can obtain being applicable to solvent of the present invention.And the like, can correspondingly determine the consumption of pH regulator agent according to the volume of solvent precursor A, because the consumption of pH regulator agent is directly proportional with the volume of solvent precursor A.
Described osmotic pressure regulator can be the various osmotic pressure regulators that are applicable to eye drop of routine, for example, can be selected from least a in glycerol, potassium chloride, sodium chloride, boric acid, Borax, mannitol or the sorbitol.
Described pH regulator agent can for example can be hydrochloric acid or sodium hydroxide for the various pH regulator agent that are applicable to eye drop of routine.
Described antiseptic can be the various antiseptic that are applicable to eye drop of routine, for example, can be selected from least a in benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate and the chlorobutanol.
Described surfactant can for example, can select polyoxyethylene sorbitan monoleate for the various surfactants that are applicable to eye drop of routine.
Described viscosity modifier can be the various viscosity modifiers that are applicable to eye drop of routine, for example, can be selected from least a in hypromellose, polyvinyl alcohol and the hyaluronic acid sodium.
Described antioxidant can for example, can select disodium edetate for the various antioxidant that are applicable to eye drop of routine.
Described solid-state drug and solvent can also contain other acceptable adjuvant of pharmacy that can not influence eye drop character.
Make after solid-state drug and the solvent, solid-state drug and solvent are packed independently.In use, individual packages is separately opened, solid-state drug is joined in the solvent dissolving fully or be uniformly dispersed and get final product.There is no particular limitation for the consumption of solid-state drug and solvent, as long as make the amount of active component contained in the eye drop that obtains reach requirement, for example contains 0.053 milligram of active component in every milliliter of eye drop.
Below by embodiment the present invention is described in more detail.
The present invention shows through the medicine stability experimentation, and is more stable at normal temperatures.
Following each embodiment only is used for illustrating the present invention.
Embodiment 1
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.8g
Taurine 75g
Boric acid 12g
Dehydrated alcohol 40ml
??????????????????????????
The dedicated solvent prescription:
Glycerol 21.0g
Disodium edetate 0.010g
Polyoxyethylene sorbitan monoleate 0.050g
Benzalkonium bromide 0.050g
Water for injection adds to 1000ml
??????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; drying, granulate is measured the pirenoxine sodium content; the calculating sheet is heavy; make every to contain anhydrous Bernetine Sodium 0.8mg, tabletting, aluminum-plastic packaged.
(2) get water for injection, add glycerol, disodium edetate, polyoxyethylene sorbitan monoleate, benzalkonium bromide, stir and make dissolving, heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 in the tablet that makes in the step (1), jolting is dissolved it fully, and with dilute hydrochloric acid adjust pH to 4.05, the consumption of record dilute hydrochloric acid is a.In remaining solvent precursor, add the dilute hydrochloric acid of 10.1a, stir evenly, cross 0.45 μ m film, by every 15ml packing.
Embodiment 2
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.85g
Taurine 65g
Borax 8g
Dehydrated alcohol 40ml
?????????????????????????
The dedicated solvent prescription:
Potassium chloride 1.5g
Boric acid 13g
Ethyl hydroxybenzoate 0.3g
Water for injection adds to 1000ml
???????????????????????????????????
Preparation method:
(1) gets taurine and Borax, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; dry; granulate is measured the pirenoxine sodium content, calculates single packed weight; make every single packing contain anhydrous Bernetine Sodium 0.85mg, aluminum-plastic packaged packing.
(2) get water for injection, add ethyl hydroxybenzoate, heated and stirred makes dissolving, adds potassium chloride and boric acid again, and heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 single packing solid drugs that make in the step (1), jolting is dissolved it fully, and with dilute hydrochloric acid adjust pH to 4.2, the consumption of record hydrochloric acid is b.In remaining solvent precursor, add 10.1b hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Embodiment 3
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.85g
Taurine 70g
Boric acid 12g
Hypromellose 2.0
????????????????????
The dedicated solvent prescription:
Potassium chloride 1.6g
Boric acid 12g
Borax 0.08g
Methyl hydroxybenzoate 0.2g
Propyl hydroxybenzoate 0.1g
Water for injection adds to 1000ml
??????????????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing, other gets hypromellose, makes 1% solution with the water for injection dissolving; add in the said mixture, granulate drying; granulate is measured the pirenoxine sodium content, and it is heavy to calculate sheet; make every to contain anhydrous Bernetine Sodium 0.8mg, tabletting, aluminum-plastic packaged.
(2) get water for injection, add potassium chloride, boric acid, Borax, methyl hydroxybenzoate, propyl hydroxybenzoate, heated and stirred makes dissolving, and heat sterilization is chilled to room temperature, adds water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 single packing solid drugs that make in the step (1), jolting is dissolved it fully, and with dilute hydrochloric acid adjust pH to 4.3, the consumption of record hydrochloric acid is c.In remaining solvent precursor, add 10.1c hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Embodiment 4
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.8g
Taurine 72g
Boric acid 13g
Dehydrated alcohol 40ml
????????????????????????????
The dedicated solvent prescription:
Potassium chloride 9.25g
Disodium edetate 0.010g
Polyoxyethylene sorbitan monoleate 0.050g
Chlorobutanol 1g
Water for injection adds to 1000ml
??????????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; drying, granulate is measured the pirenoxine sodium content; the calculating sheet is heavy; make the every anhydrous Bernetine Sodium 0.8mg that contains, tabletting, aluminum-plastic packaged.
(2) get water for injection, add potassium chloride, disodium edetate, chlorobutanol, polyoxyethylene sorbitan monoleate, heating is then stirred and is made dissolving, and heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90mml solvent precursor, toward wherein adding 6 in the tablet and the jolting that make in the step (1) it is dissolved fully, with dilute hydrochloric acid adjust pH to 4.4, the consumption of record dilute hydrochloric acid is d.In remaining solvent precursor, add the 10.1d dilute hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Embodiment 5
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.8g
Taurine 72g
Boric acid 13g
Dehydrated alcohol 40ml
???????????????????????
The dedicated solvent prescription:
Potassium chloride 9.25g
Disodium edetate 0.010g
Polyoxyethylene sorbitan monoleate 0.050g
Chlorobutanol 1g
Water for injection adds to 1000ml
????????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; drying, granulate is measured the pirenoxine sodium content; the calculating sheet is heavy; make the every anhydrous Bernetine Sodium 0.8mg that contains, tabletting, aluminum-plastic packaged.
(2) get water for injection, add potassium chloride, disodium edetate, polyoxyethylene sorbitan monoleate, chlorobutanol, heating is stirred and is made dissolving, and heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 joltings of tablet that make in the step (1) it is dissolved fully, with dilute hydrochloric acid adjust pH to 4.45, the consumption of record dilute hydrochloric acid is e.In remaining solvent precursor, add the 10.1e dilute hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Embodiment 6
Make eye drop according to the method identical with embodiment 5, different is, the pH of solvent precursor is adjusted to 4.02.
Embodiment 7
Make eye drop according to the method identical with embodiment 5, different is, the pH of solvent precursor is adjusted to 4.48.
Comparative Examples 1
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.8g
Taurine 75g
Boric acid 12g
Dehydrated alcohol 40ml
??????????????????????
The dedicated solvent prescription:
Glycerol 21.0g
Disodium edetate 0.010g
Polyoxyethylene sorbitan monoleate 0.050g
Benzalkonium bromide 0.050g
Water for injection adds to 1000ml
???????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; drying, granulate is measured the pirenoxine sodium content; the calculating sheet is heavy; make every to contain anhydrous Bernetine Sodium 0.8mg, tabletting, aluminum-plastic packaged.
(2) get water for injection, add glycerol, disodium edetate, polyoxyethylene sorbitan monoleate, benzalkonium bromide, stir and make dissolving, heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 in the tablet and the jolting that make in the step (1) it is dissolved fully, with dilute hydrochloric acid adjust pH to 5.0, the consumption of record dilute hydrochloric acid is f.In remaining solvent precursor, add the 10.1f dilute hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Comparative Examples 2
The Bernetine Sodium slice prescription:
Bernetine Sodium 0.8g
Taurine 75g
Boric acid 12g
Dehydrated alcohol 40ml
????????????????????????
The dedicated solvent prescription:
Glycerol 21.0g
Disodium edetate 0.010g
Polyoxyethylene sorbitan monoleate 0.050g
Benzalkonium bromide 0.050g
Water for injection adds to 1000ml
??????????????????????????
Preparation method:
(1) gets taurine and boric acid, pulverize, cross 80 mesh sieves; mixing is crossed Bernetine Sodium 120 mesh sieves again, adds in the above-mentioned adjuvant; mixing adds dehydrated alcohol again, granulates; drying, granulate is measured the pirenoxine sodium content; the calculating sheet is heavy; make the every anhydrous Bernetine Sodium 0.8mg that contains, tabletting, aluminum-plastic packaged.
(2) get water for injection, add glycerol, disodium edetate, polyoxyethylene sorbitan monoleate, benzalkonium bromide, stir and make dissolving, heat sterilization is added water for injection to 1000ml, makes 1000ml solvent precursor.Get 90ml solvent precursor, toward wherein adding 6 in the tablet and the jolting that make in the step (1) it is dissolved fully, with dilute hydrochloric acid adjust pH to 6.0, the consumption of record dilute hydrochloric acid is g.In remaining solvent precursor, add the 10.1g dilute hydrochloric acid, cross 0.45 μ m film, by every 15ml packing.
Comparative Examples 3
Make eye drop according to the method identical with Comparative Examples 2, different is, the pH of solvent precursor is adjusted to 3.9.
Performance test
Get the solvent each 10 (every 15ml) that obtains among embodiment 1-7 and the Comparative Examples 1-3, in every, add the corresponding embodiment of 1 or one single packing and the Bernetine Sodium solid drugs that Comparative Examples makes then, after the dissolving, after placing 5 days, 10 days and 20 days under 25 ℃, respectively survey the content of a Bernetine Sodium fully with high-efficient liquid phase technique.
Chromatographic condition: with octyl group silane group silica gel is filler, is mobile phase with 0.1mol/L sodium dihydrogen phosphate (regulating pH value to 6.0 with a sodium hydroxide test solution) methanol one acetonitrile (70: 30: 10); The detection wavelength is 433nm.
The algoscopy precision is measured this product 2ml, puts in the 20ml measuring bottle, is diluted to scale with mobile phase, shakes up, as need testing solution; In addition precision takes by weighing the about 28mg of Bernetine Sodium reference substance (raw material), dissolves and is diluted to 5.6 μ g/ml, product solution in contrast with mobile phase.Measure each 20 μ l of above-mentioned two kinds of solution, inject chromatograph of liquid respectively, the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The result is as shown in table 1.
Table 1
| 0 day content | 5 days content | 10 days content | 20 days content | |
| Embodiment 1 | ??97.4％ | ??97.2％ | ??96.5％ | ??95.2％ |
| Embodiment 2 | ??103.2％ | ??100.5％ | ??97.1％ | ??93.4％ |
| Embodiment 3 | ??105.2％ | ??102.8％ | ??99.1％ | ??95.5％ |
| Embodiment 4 | ??100.3％ | ??97.1％ | ??94.3％ | ??91.2％ |
| Embodiment 5 | ??98.7％ | ??95.5％ | ??92.9％ | ??90.8％ |
| Embodiment 6 | ??98.7％ | ??95.3％ | ??92.4％ | ??90.2％ |
| Embodiment 7 | ??98.7％ | ??95.2％ | ??92.1％ | ??90.1％ |
| Comparative Examples 1 | ??99.4％ | ??89.1％ | ??76.2％ | ??62.3％ |
| Comparative Examples 2 | ??100.1％ | ??88.2％ | ??74.6％ | ??61.8％ |
| Comparative Examples 3 | ??100.1％ | ??88.7％ | ??74.9％ | ??62.1％ |
From the result shown in the table 1 as can be seen, the content that eye drop room temperature provided by the invention is placed after 20 days down is more than 90%, thereby has prolonged the effect duration after using first, and the content that the eye drop room temperature of Comparative Examples 1-2 is placed after 20 days down only is 65 following %.
Claims (8)
1. one kind is used for cataractous eye drop, it is characterized in that, this eye drop comprises the solid-state drug of independent packaging and is used to dissolve or disperse the solvent of this solid-state drug, described solid-state drug contains active component and pharmacy acceptable auxiliary, described active component is a Bernetine Sodium, wherein, in every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.045-0.060mg or the pH value of dispersion liquid for greater than 4 to less than 4.5.
2. eye drop according to claim 1, wherein, described adjuvant is at least a in taurine, boric acid and the Borax, the weight ratio of active component and adjuvant is 1: 60-180.
3. eye drop according to claim 1, wherein, the pH value of described solution or dispersion liquid is 4.05-4.45.
4. eye drop according to claim 1, wherein, dissolving or disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.053mmg or the pH value of dispersion liquid is 4.05-4.45 in every milliliter of solvent.
5. according to claim 1,3 or 4 described eye drops, wherein, described solvent contains water for injection and pH regulator agent, the content of pH regulator agent make in every milliliter of solvent dissolving disperse to contain the solution that obtains after the solid-state drug of the anhydrous Bernetine Sodium of 0.053mg or the pH value of dispersion liquid in claim 1,3 or 4 scope.
6. eye drop according to claim 5, wherein, described pH regulator agent is hydrochloric acid or sodium hydroxide.
7. eye drop according to claim 5, wherein, described solvent also contains additive, and additive is selected from least a in osmotic pressure regulator, antiseptic, surfactant, viscosity modifier and the antioxidant.
8. eye drop according to claim 7, wherein, described osmotic pressure regulator is selected from least a in glycerol, potassium chloride, sodium chloride, boric acid, Borax, mannitol or the sorbitol; Antiseptic is selected from least a in benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate and the chlorobutanol; Surfactant is selected from polyoxyethylene sorbitan monoleate; Viscosity modifier is selected from least a in hypromellose, polyvinyl alcohol and the hyaluronic acid sodium; Antioxidant is selected from disodium edetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101263501A CN101822677B (en) | 2009-03-03 | 2009-03-03 | Eye drops for cataract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101263501A CN101822677B (en) | 2009-03-03 | 2009-03-03 | Eye drops for cataract |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101822677A true CN101822677A (en) | 2010-09-08 |
| CN101822677B CN101822677B (en) | 2012-05-30 |
Family
ID=42686981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101263501A Expired - Fee Related CN101822677B (en) | 2009-03-03 | 2009-03-03 | Eye drops for cataract |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101822677B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211754A (en) * | 2012-01-19 | 2013-07-24 | 武汉诺安药业有限公司 | Production method of sterile stable pirenoxine sodium eye drops |
| 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 |
| CN109481434A (en) * | 2018-12-18 | 2019-03-19 | 湖北远大天天明制药有限公司 | Eye drops, and the preparation method and application thereof |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
| CN112823784A (en) * | 2019-11-20 | 2021-05-21 | 湖北远大天天明制药有限公司 | Prenoxinate sodium eye drops and solution for ocular administration |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100998863A (en) * | 2006-01-12 | 2007-07-18 | 上海新药研究开发中心 | N-acetyl carnosine eye drops for preventing and treating cataract and its preparation method |
| CN1895218A (en) * | 2006-06-22 | 2007-01-17 | 武汉远大制药集团有限公司 | Pyrrolechrisxi and its sodium-salt eye-gel preparation and its making method |
| CN101336923A (en) * | 2007-07-06 | 2009-01-07 | 肖正连 | Eye in-situ gel of pirenoxine sodium |
-
2009
- 2009-03-03 CN CN2009101263501A patent/CN101822677B/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211754A (en) * | 2012-01-19 | 2013-07-24 | 武汉诺安药业有限公司 | Production method of sterile stable pirenoxine sodium eye drops |
| 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 |
| CN109481434A (en) * | 2018-12-18 | 2019-03-19 | 湖北远大天天明制药有限公司 | Eye drops, and the preparation method and application thereof |
| CN109481434B (en) * | 2018-12-18 | 2020-11-10 | 湖北远大天天明制药有限公司 | Eye drops, preparation method and application thereof |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
| CN112823784A (en) * | 2019-11-20 | 2021-05-21 | 湖北远大天天明制药有限公司 | Prenoxinate sodium eye drops and solution for ocular administration |
| CN112823784B (en) * | 2019-11-20 | 2022-09-16 | 湖北远大天天明制药有限公司 | Prenoxinate sodium eye drops and solution for ocular administration |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101822677B (en) | 2012-05-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101822677B (en) | Eye drops for cataract | |
| CN102861106B (en) | Preparation method of compound paracetamol and amantadine pellets | |
| WO1995013794A1 (en) | Process for producing stable medicinal composition, and pharmaceutical preparation | |
| CN105213322A (en) | Pharmaceutical composition prepared by a kind of dry granulation process | |
| CN103127024B (en) | Stable disodium adenosine triphosphate tablet | |
| CN102716102B (en) | Mecobalamin tablet and preparation method thereof | |
| CN106606476A (en) | Ibuprofen suspension drops and preparation method thereof | |
| CN112022826A (en) | Mecobalamin tablet and preparation method thereof | |
| CN103610658B (en) | Immunomodulator slow-release preparation and preparation method thereof | |
| CN101623278A (en) | Medicinal composition containing levodopa and benserazide hydrochloride | |
| CN102228423A (en) | Tolvaptan oral solid medicinal composition and preparation method thereof | |
| CN108261397B (en) | High-content amoxicillin soluble powder and preparation method thereof | |
| CN103110602B (en) | Disodium adenosine triphosphate troche medical composition | |
| CN104173370A (en) | Calcium-containing effervescent tablet and preparation method and application | |
| CN106727396A (en) | A kind of II crystal linezolid piece and preparation method thereof | |
| CN104188928B (en) | A kind of Valaciclovir hydrochloride tablet and preparation method thereof | |
| CN116406257A (en) | Pharmaceutical compositions and methods for enhancing the solubility of poorly soluble active pharmaceutical ingredients | |
| CN110354090B (en) | Metformin hydrochloride sustained release tablet and preparation method thereof | |
| CN100415230C (en) | Dispersion tablets of penicillin V potassium, and its preparing method | |
| TW202002996A (en) | Peptide-containing formulations | |
| CN107753438A (en) | A kind of children's calcium carbonate D3Particle | |
| CN102846572A (en) | Diclofenac sodium sustained release tablet and preparation method thereof | |
| CN107890462A (en) | A kind of pazopanib tablet composition | |
| Lodha et al. | Formulation and evaluation of transparent ibuprofen soft gelatin capsule | |
| CN103127108A (en) | Telmisartan amlodipine tablet, and preparation method and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wu Wenyao Inventor after: Cai Kui Inventor before: Wu Wenyao Inventor before: Cai Gui |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: WU WENYAO CAI GUI TO: WU WENYAO CAI KUI |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120530 Termination date: 20140303 |