JPH01213228A - Aqueous suspension eye drop - Google Patents
Aqueous suspension eye dropInfo
- Publication number
- JPH01213228A JPH01213228A JP63041572A JP4157288A JPH01213228A JP H01213228 A JPH01213228 A JP H01213228A JP 63041572 A JP63041572 A JP 63041572A JP 4157288 A JP4157288 A JP 4157288A JP H01213228 A JPH01213228 A JP H01213228A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- water
- aluminum
- soluble
- eye drop
- 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 24
- 239000007900 aqueous suspension Substances 0.000 title claims abstract description 13
- 229940079593 drug Drugs 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims abstract description 11
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims abstract description 8
- OKPNYGAWTYOBFZ-UHFFFAOYSA-N Pirenoxine Chemical compound C12=NC3=CC=CC=C3OC2=CC(=O)C2=C1C(=O)C=C(C(=O)O)N2 OKPNYGAWTYOBFZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960003957 dexamethasone Drugs 0.000 claims abstract description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims abstract description 4
- 229960001048 fluorometholone Drugs 0.000 claims abstract description 4
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 claims abstract description 4
- 229960000905 indomethacin Drugs 0.000 claims abstract description 4
- 229960005071 pirenoxine Drugs 0.000 claims abstract description 4
- NCXMLFZGDNKEPB-UHFFFAOYSA-N Pimaricin Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCC(C)OC(=O)C=CC2OC2CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 NCXMLFZGDNKEPB-UHFFFAOYSA-N 0.000 claims abstract description 3
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 claims abstract description 3
- 229960001067 hydrocortisone acetate Drugs 0.000 claims abstract description 3
- 229960003255 natamycin Drugs 0.000 claims abstract description 3
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 claims abstract description 3
- FBRAWBYQGRLCEK-UHFFFAOYSA-N [17-(2-chloroacetyl)-9-fluoro-10,13,16-trimethyl-3,11-dioxo-7,8,12,14,15,16-hexahydro-6h-cyclopenta[a]phenanthren-17-yl] butanoate Chemical compound C1CC2=CC(=O)C=CC2(C)C2(F)C1C1CC(C)C(C(=O)CCl)(OC(=O)CCC)C1(C)CC2=O FBRAWBYQGRLCEK-UHFFFAOYSA-N 0.000 claims abstract 2
- 229960005465 clobetasone butyrate Drugs 0.000 claims abstract 2
- 229940012356 eye drops Drugs 0.000 claims description 11
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract description 16
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 abstract description 4
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 abstract description 3
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 abstract description 3
- 239000000872 buffer Substances 0.000 abstract description 3
- 239000006196 drop Substances 0.000 abstract description 3
- 239000003755 preservative agent Substances 0.000 abstract description 3
- 239000004094 surface-active agent Substances 0.000 abstract description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical class [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 abstract description 2
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 230000002335 preservative effect Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 18
- 238000009472 formulation Methods 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000007794 irritation Effects 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 229960000686 benzalkonium chloride Drugs 0.000 description 4
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 description 4
- 235000019800 disodium phosphate Nutrition 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 4
- 235000019799 monosodium phosphate Nutrition 0.000 description 4
- -1 polyoxyethylene Polymers 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 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 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229910021538 borax Inorganic materials 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 235000010338 boric acid Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 239000004328 sodium tetraborate Substances 0.000 description 3
- 235000010339 sodium tetraborate Nutrition 0.000 description 3
- 206010015946 Eye irritation Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 229940067596 butylparaben Drugs 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 231100000013 eye irritation Toxicity 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 231100000635 Draize test Toxicity 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229960001716 benzalkonium Drugs 0.000 description 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
「産業上の利用分野」
本発明は水溶性アルミニウム塩を配合することにより、
分散性の良い水性懸濁点眼剤を提供するものである。Detailed Description of the Invention "Industrial Application Field" The present invention provides
The present invention provides an aqueous suspension eye drop with good dispersibility.
「従来技術及び発明が解決しようとする課題」水に対す
る溶解度の低い薬物を点眼用として製剤化する場合、薬
物を懸濁させた水性点眼剤とすることが考えられる。こ
のような水性懸濁点眼剤は長時間放置すると薬物が沈降
するため、点眼時には容器を振とうし再分散して用いな
ければならない。ところが、沈降した薬物がケーキング
などの２次凝集をおこすと容易に再分散しなくなり、点
眼時に長時間振とうしなければならない。"Prior Art and Problems to be Solved by the Invention" When formulating a drug with low solubility in water as an eye drop, it is conceivable to formulate an aqueous eye drop in which the drug is suspended. If such aqueous suspension eye drops are left for a long time, the drug will settle, so the container must be shaken and redispersed before use. However, if the precipitated drug causes secondary aggregation such as caking, it cannot be easily redispersed, and the drug must be shaken for a long time when instilled into the eye.
再分散性を良くする方法の一つとして薬物の粒子サイズ
を大きくすることが考えられるが、点眼剤の場合大きな
粒子は眼に対する異物感が生じるという欠点がある。One possible method for improving redispersibility is to increase the particle size of the drug, but in the case of eye drops, large particles have the disadvantage of causing a foreign body sensation to the eyes.
このため、分散性にすぐれた水性懸濁点眼剤を検討する
必要があった。For this reason, it was necessary to consider an aqueous suspension eye drop with excellent dispersibility.
「課題を解決するための手段」
本発明者らは分散性のすぐれた水性Ｍ濁点成剤を鋭意検
討した結果、水溶性アルミニウム塩を配合することによ
り課題が解決できることを見い出した。"Means for Solving the Problems" The inventors of the present invention have conducted intensive studies on aqueous M cloud point forming agents with excellent dispersibility, and have found that the problems can be solved by incorporating a water-soluble aluminum salt.
「発明の開示」
水性懸濁点眼剤は水に対する溶解度の低い薬物を製剤化
する時に用いられる。このよう表懸濁型の点眼剤は使用
時に再分散させなければならないが、２次凝集が生じや
すい薬物では長時聞損とうしなければならなかった。薬
物の粒子サイズを大きくすれば再分散性は良くなるもの
の、眼に対する異物感が生じる欠点がある。DISCLOSURE OF THE INVENTION Aqueous suspension eye drops are used when formulating drugs with low solubility in water. Such surface suspension type eye drops must be redispersed before use, but drugs that tend to cause secondary aggregation must be left unused for a long time. Although increasing the particle size of the drug improves redispersibility, it has the drawback of causing a foreign body sensation to the eyes.
そこで、本発明者らはこの課題について鋭意検討した結
果、水溶性アルミニウム塩を配合することにより再分散
性にすぐれた水性懸濁点眼剤（以下、本発明製剤という
。）が得られることを見い出した。The inventors of the present invention conducted extensive studies on this issue and found that an aqueous suspension eye drop with excellent redispersibility (hereinafter referred to as the formulation of the present invention) can be obtained by incorporating a water-soluble aluminum salt. Ta.
本発明製剤における水溶性アルミ、ニウム塩とは塩化ア
ルミニウム、硫酸アルミニウム、硝酸アルミニウムなど
の水に溶解するアルミニウム塩を示す。アルミニウム塩
の濃度は薬物の分散性が良くなる様に設定するが、好ま
しくは０．００５〜１．０ ％である。The water-soluble aluminum and nium salts in the formulation of the present invention refer to aluminum salts that are soluble in water, such as aluminum chloride, aluminum sulfate, and aluminum nitrate. The concentration of the aluminum salt is set so as to improve the dispersibility of the drug, and is preferably 0.005 to 1.0%.
本発明製剤に用いられる薬剤は水に対する溶解度の低い
ものであれば特に制限はなく、酪酸クロベタシン、フル
オロメトロン、酢酸ハイドロコーチゾン、デキサメサゾ
ンなどのステロイドやインドメタシン、ピレノキシン、
ピマリシンなどが例としてあげられる。これらの薬物の
波度は薬物の種類、薬効などに応じて適宜選択できる。The drugs used in the preparation of the present invention are not particularly limited as long as they have low solubility in water, and include steroids such as clobetacin butyrate, fluorometholone, hydrocortisone acetate, dexamethasone, indomethacin, pirenoxine,
An example is pimaricin. The intensity of these drugs can be appropriately selected depending on the type of drug, efficacy, etc.
本発明の効果は「再分散性試験」の項で詳しく述べるが
、本発明製剤の再分散性は水溶性アルミニウム塩を配合
しないものと比較して格段にすぐれておシ、使用時に容
易に再分散できることを示している。又、「刺激性試験
」の項で述べるように本発明製剤は眼に対する刺激もな
く、安全性にも問題ないことが確認された。The effects of the present invention will be described in detail in the "Redispersibility Test" section, but the redispersibility of the formulation of the present invention is much better than that of formulations that do not contain water-soluble aluminum salts, and it can be easily redispersed during use. This shows that it can be dispersed. Furthermore, as described in the section "Irritation Test", it was confirmed that the preparation of the present invention did not cause any irritation to the eyes and had no safety problems.
本発明製剤には点眼剤として通常用いられている添加剤
を加えても良く、例えば塩化ナトリウム、マンニトール
、グリセリンなどの等張化剤、リン酸水素ナトリウム、
リン酸二水素ナトリウム、ホウ酸、ホウ砂などの緩衝剤
、 ポリソルベート８０、ポリオキシエチレン硬化ヒマ
シ油、ショ糖脂肪酸エステルなどの界面活性剤、塩化ベ
ンザルコニウム、パラオキシ安息香酸（以下パラベンと
いう）エステルなどの防腐剤、水酸化ナトリウム、塩酸
などのｐＨ調節剤などがあげられる。Additives commonly used in eye drops may be added to the formulation of the present invention, such as isotonic agents such as sodium chloride, mannitol, and glycerin, sodium hydrogen phosphate,
Buffers such as sodium dihydrogen phosphate, boric acid, borax, surfactants such as polysorbate 80, polyoxyethylene hydrogenated castor oil, sucrose fatty acid ester, benzalkonium chloride, paraoxybenzoic acid (hereinafter referred to as paraben) ester Examples include preservatives such as, pH regulators such as sodium hydroxide, and hydrochloric acid.
本発明製剤の一般的な製法としては次のものがあげられ
る。滅菌精製水に水溶性アルミニウム塩を加え、必要に
応じて等張化剤、緩衝剤、 界面活性剤、防腐剤などを
加える。必要ならば濾過滅菌した後、この溶液に薬剤を
加え、ホモジナイザーを用いて懸濁させ本発明製剤を得
る。又、ホモジナイザーのかわシに超音波を照射して懸
濁させてもよい。The following is a general method for producing the preparation of the present invention. Add a water-soluble aluminum salt to sterile purified water, and add tonicity agents, buffers, surfactants, preservatives, etc. as necessary. After sterilization by filtration if necessary, a drug is added to this solution and suspended using a homogenizer to obtain the preparation of the present invention. Alternatively, the suspension may be suspended by irradiating ultrasonic waves onto the sieve of the homogenizer.
本発明製剤のｐＨは点眼剤として通常用いられているも
のであれば良く、好ましくは４．５〜８である。The pH of the formulation of the present invention may be any pH commonly used as eye drops, preferably from 4.5 to 8.
本発明製剤は、通常１回１〜数滴、１日１〜数回投与す
ることができる。The preparation of the present invention can be administered usually one to several drops at a time, one to several times a day.
以下に実施例を示す。Examples are shown below.
「実施例」
実施例１
処方Ａ
１００Ｍ１中
酪酸クロベタシン ０．１ｙ塩化アルミニウ
ム ｏ、ｏ ｓ ｙポリソルベー）８０
０．０３ｙ塩化ナトリウム ０．
８ｙリン酸二水素ナトリウム ０．３ｙ塩化ベ
ンザルコニウム ｏ、ｏ ｏ ｓ ｐ水酸化
ナトリウム 適量
滅菌精製水 ｌ
製法
滅菌精製水８０−に塩化アルミニウム、ポリソルベート
８０、塩化ナトリウム、リン酸二水素ナトリウム、塩化
ベンザルコニウムを加えて溶解する。"Example" Example 1 Formulation A 100M clobetacin butyrate 0.1y aluminum chloride o, o sy polysorbate) 80
0.03y Sodium chloride 0.
8y Sodium dihydrogen phosphate 0.3y Benzalkonium chloride o, o o sp Sodium hydroxide Appropriate amount Sterile purified water l Manufacturing method Sterile purified water 80-, aluminum chloride, polysorbate 80, sodium chloride, sodium dihydrogen phosphate, chloride Add benzalkonium and dissolve.
水酸化ナトリウムを加えてｐＨを６に調節した後、滅菌
精製水を加えて全景を１００１ｎｌとする。この溶液に
酪酸クロベタシンを加えた後、ホモジナイザーを用いて
懸濁させ本発明の水性懸濁点眼剤を得た。After adjusting the pH to 6 by adding sodium hydroxide, sterile purified water is added to bring the total volume to 1001 nl. After adding clobetacin butyrate to this solution, the mixture was suspended using a homogenizer to obtain an aqueous suspension eye drop of the present invention.
実施例１と同様の方法で処方Ｂ−Ｅの点眼剤を得た。Eye drops of formulation BE were obtained in the same manner as in Example 1.
処方Ｂ
１ＯＯ１ａｌ中
酪酸クロベタシン ０．０５ｙ塩化アルミニ
ウム ０．０３ｙポリソルベー）８０
０．０３ｙマンニトール １．８
２グリセリン １．２ｙ
リン酸水素ナトリウム ０．３ｙメチルパラベン
０．０２６ ｐプロピルパラベン
０．０１４９希塩酸
適量
滅菌精製水
処方Ｃ
１００ｄ中
フルオロメトロン ０．１ｙ塩化アルミニ
ウム ０，１２ポリオキシエチレン硬化ヒマ
シ油 ０．０５ｙ塩化ナトリウム
０．７ｙυ／酸水素ナトリウム ０．５ｙリン酸
二水素ナトリウム 適量塩化ベンザルコニウム
ｏ、ｏｏｓｙ滅菌精製水
適量
処方Ｄ
１０〇−中
デキサメサゾン ０．１ｙ硝酸アルミニウ
ム ０．０５ｙシヨ糖脂肪酸エステル
０．０５１マンニトール ２．０ｙグ
リセリン １．２ｙ
メチルパラベン ０．０３ｙプロピルパ
ラベン ０．０１８ｙ希塩酸
適量
水酸化ナトリウム
滅菌精製水
処方Ｅ
１００ ｍｌ中
インドメタシン ０．５ｙ硫酸アルミニウ
ム ０．５９ポリソルベート８０
０．１ ｙリン酸水素ナトリウム ０．１ｙ塩
化ベンザルコニウム ０．００５ｙ希塩酸
適量
滅菌精製水
実施例２
処方Ｆ
１００ｄ中
ピレノキシン ｏ、ｏｏｓｙ塩化アルミニ
ウム ０．０２ｙホウ酸
１．４２
ホウ砂 適量
エチルパラベン ０．０２４１ブチルパラベ
ン ０．０１６ Ｆ？滅菌ｎｆＡ水
適量
製法
８０℃に熱した滅菌￥ｆＩｓ水８０ｒｎｌにエチルノ（
ラペン、ブチルパラベン、ホウ酸を溶解する。室温に冷
却した後、塩化アルミニウムを加える。ホウ砂を用いて
ｐ）Ｉを５．５に調節した後、Ｖ、画情製水を加えて全
量を１００ ｍｌとする。この溶液にビレ、ツキシンを
加え、ホモジナイザーで９濁させる。Formulation B Clobetacin butyrate 0.05y aluminum chloride 0.03y polysorbate in 1OO1al) 80
0.03y mannitol 1.8
2 Glycerin 1.2y Sodium hydrogen phosphate 0.3y Methylparaben 0.026 p Propylparaben
0.0149 dilute hydrochloric acid
Appropriate amount of sterile purified water formulation C 100d fluorometholone 0.1y aluminum chloride 0.12 polyoxyethylene hydrogenated castor oil 0.05y sodium chloride
0.7yυ/sodium hydrogen phosphate 0.5y sodium dihydrogen phosphate appropriate amount benzalkonium chloride o, oosy sterile purified water
Proper dosage prescription D 100-medium dexamethasone 0.1y aluminum nitrate 0.05y sucrose fatty acid ester
0.051 mannitol 2.0y glycerin 1.2y methylparaben 0.03y propylparaben 0.018y dilute hydrochloric acid
Appropriate amount of sodium hydroxide Sterilized purified water Formula E 100 ml Indomethacin 0.5y Aluminum sulfate 0.59 Polysorbate 80
0.1y Sodium hydrogen phosphate 0.1y Benzalkonium chloride 0.005y Dilute hydrochloric acid
Appropriate amount of sterile purified water Example 2 Prescription F 100d Pirenoxine o, oosy Aluminum chloride 0.02y Boric acid
1.42 Borax Appropriate amount Ethylparaben 0.0241 Butylparaben 0.016 F? Sterile nfA water
Appropriate amount Preparation method: Add 80 rnl of sterilized water heated to 80°C to
Dissolve Lapen, butylparaben, and boric acid. After cooling to room temperature, aluminum chloride is added. After adjusting p)I to 5.5 using borax, add V and Gejo Seisui to bring the total volume to 100 ml. Add fillet and tuxin to this solution and make it cloudy with a homogenizer.
再分散性試験
点眼容器の底に沈降した薬物の再分散性について調べる
ため次のような実験を行々つた。Redispersibility test The following experiment was conducted to investigate the redispersibility of the drug that had settled at the bottom of the eye drop container.
あらかじめ５ｄの点眼容器に本発明製剤とその処方から
アルミニウム塩を除いたものを入れておき薬物を沈降さ
せる。次に点眼容器を２Ｏｒｐｍの速度で回転させ、沈
降していた薬物が均一に分散するまでの回転数を測定し
た。その結果の一例を表に示す。The preparation of the present invention and its formulation minus the aluminum salt are placed in a 5d eye drop container in advance, and the drug is allowed to precipitate. Next, the eye drop container was rotated at a speed of 2 Orpm, and the number of rotations until the precipitated drug was uniformly dispersed was measured. An example of the results is shown in the table.
表
表に示すように本発明製剤はすみやかに再分散するがア
ルミニウム塩を含まないものはかなりの時間を要してい
る。この結果から本発明製剤の効果は明らかである。As shown in the table, the formulation of the present invention is quickly redispersed, but the formulation that does not contain aluminum salt takes a considerable amount of time. From this result, the effect of the formulation of the present invention is clear.
刺激性試験
点眼剤の眼刺激性を調べる指標として、通常ウサギの瞬
目回数の測定とドレーズ試験が行なわれる。本発明製剤
の一例として実施例１の処方Ａの水性懸濁点眼剤を用い
、生理食塩水をコントロールとして比較検討した。その
結果を下記に示す。Irritation test As an indicator for examining the eye irritation potential of eye drops, measurement of the number of blinks in rabbits and the Draize test are usually performed. A comparative study was conducted using the aqueous suspension eye drops of Formulation A of Example 1 as an example of the formulation of the present invention, and using physiological saline as a control. The results are shown below.
ウサギに１滴点眼した後の１分間の瞬目回数は両者に差
がなく、刺激は認められなかった。There was no difference in the number of blinks per minute after one drop was instilled into the eyes of rabbits, and no irritation was observed.
次に１０回点眼した後、改良ドレーズ法（福井ら、現代
の臨床、４，２７７ （１９７０）’）により採点した
ところ、本発明製剤、生理食塩液のいずれにも障害は認
められず、本発明製剤には眼刺激性がない事を示してい
る。Next, after applying the instillation 10 times, the eyes were scored using the modified Draize method (Fukui et al., Modern Clinical Practice, 4,277 (1970)'). This shows that the invented formulation does not cause eye irritation.
「発明の効果」
本発明の水性ｉ濁点成剤は再分散性が良く、更に刺激性
がないというすぐれた効果を有するものでちる。"Effects of the Invention" The aqueous cloud point forming agent of the present invention has excellent redispersibility and is free from irritation.
Claims (3)
の分散性を高めたことを特徴とする水性懸濁点眼剤。(1) An aqueous suspension eye drop characterized by having improved drug dispersibility by incorporating a water-soluble aluminum salt.
載の水性懸濁点眼剤。(2) The aqueous suspension eye drops according to claim 1, wherein the drug is sparingly soluble in water.
酸ハイドロコーチゾン、デキサメサゾン、インドメタシ
ン、ピレノキシンまたはピマリシンである特許請求の範
囲第１項記載の水性懸濁点眼剤。(3) The aqueous suspension eye drops according to claim 1, wherein the drug is clobetasone butyrate, fluorometholone, hydrocortisone acetate, dexamethasone, indomethacin, pirenoxine, or pimaricin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63041572A JPH0796495B2 (en) | 1988-02-23 | 1988-02-23 | Aqueous suspension eye drops |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63041572A JPH0796495B2 (en) | 1988-02-23 | 1988-02-23 | Aqueous suspension eye drops |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01213228A true JPH01213228A (en) | 1989-08-28 |
| JPH0796495B2 JPH0796495B2 (en) | 1995-10-18 |
Family
ID=12612157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63041572A Expired - Fee Related JPH0796495B2 (en) | 1988-02-23 | 1988-02-23 | Aqueous suspension eye drops |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0796495B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037286A1 (en) * | 1998-01-22 | 1999-07-29 | Santen Pharmaceutical Co., Ltd. | Fluorometholone suspension eye drops |
| WO2008123396A1 (en) * | 2007-03-29 | 2008-10-16 | Santen Pharmaceutical Co., Ltd. | Suspension-type eye drop preparation comprising fluorometholone |
| US8746047B2 (en) | 2008-07-16 | 2014-06-10 | Pokka Corporation | Dispersion analysis method and device |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5136323A (en) * | 1974-07-26 | 1976-03-27 | Ai Ranpaato Shuromo | Shigekinitaisuru taishoshano hannoo sokuteisuru sochinarabini hoho |
-
1988
- 1988-02-23 JP JP63041572A patent/JPH0796495B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5136323A (en) * | 1974-07-26 | 1976-03-27 | Ai Ranpaato Shuromo | Shigekinitaisuru taishoshano hannoo sokuteisuru sochinarabini hoho |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037286A1 (en) * | 1998-01-22 | 1999-07-29 | Santen Pharmaceutical Co., Ltd. | Fluorometholone suspension eye drops |
| US6288049B1 (en) | 1998-01-22 | 2001-09-11 | Santen Pharmaceutical Co., Ltd. | Fluorometholone ophthalmic suspension |
| WO2008123396A1 (en) * | 2007-03-29 | 2008-10-16 | Santen Pharmaceutical Co., Ltd. | Suspension-type eye drop preparation comprising fluorometholone |
| US8746047B2 (en) | 2008-07-16 | 2014-06-10 | Pokka Corporation | Dispersion analysis method and device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0796495B2 (en) | 1995-10-18 |
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