JP3797764B2 - Light stabilizing composition - Google Patents
Light stabilizing composition Download PDFInfo
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- JP3797764B2 JP3797764B2 JP26874797A JP26874797A JP3797764B2 JP 3797764 B2 JP3797764 B2 JP 3797764B2 JP 26874797 A JP26874797 A JP 26874797A JP 26874797 A JP26874797 A JP 26874797A JP 3797764 B2 JP3797764 B2 JP 3797764B2
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- Prior art keywords
- acid
- donepezil
- organic
- dementia
- present
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- 239000000203 mixture Substances 0.000 title claims description 9
- 230000000087 stabilizing effect Effects 0.000 title 1
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 36
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 21
- 229960003530 donepezil Drugs 0.000 claims description 18
- 150000007524 organic acids Chemical class 0.000 claims description 12
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 12
- 229940005524 anti-dementia drug Drugs 0.000 claims description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 239000002664 nootropic agent Substances 0.000 claims description 6
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 6
- 229960004889 salicylic acid Drugs 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 235000002906 tartaric acid Nutrition 0.000 claims description 4
- 239000011975 tartaric acid Substances 0.000 claims description 4
- 230000000176 photostabilization Effects 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims 2
- 230000006641 stabilisation Effects 0.000 claims 1
- 238000011105 stabilization Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 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 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QYWRWHSGJDPODU-UHFFFAOYSA-N 2-(1-benzyl-2-methylpiperidin-4-yl)-5,6-dimethoxy-2,3-dihydroinden-1-one Chemical group O=C1C=2C=C(OC)C(OC)=CC=2CC1C(CC1C)CCN1CC1=CC=CC=C1 QYWRWHSGJDPODU-UHFFFAOYSA-N 0.000 description 1
- CWEHWZPCDBRUNO-WLHGVMLRSA-N 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1h-1-benzazepin-8-yl)propan-1-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=1C=C2CCCCNC2=CC=1C(=O)CCC(CC1)CCN1CC1=CC=CC=C1 CWEHWZPCDBRUNO-WLHGVMLRSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010012289 Dementia Diseases 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
- 229930195725 Mannitol Natural products 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960003135 donepezil hydrochloride Drugs 0.000 description 1
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
【０００１】
【産業上の利用分野】
本発明は、抗痴呆薬、特にドネペジルの光安定化組成物及びドネペジルの光安定化方法に関する。
【０００２】
【発明の背景及び従来技術】
近年、老人性痴呆症の介護等が社会的な問題となり、その治療薬の開発が盛んに行われている。中でもドネペジルは、アセチルコリンエステラーゼ阻害作用を有する、軽度から中等度のアルツハイマー痴呆症の治療剤としてその有用性が高く評価されている。ドネペジルは塩基性薬物であるため通常は塩酸塩として供されている。
一方、薬物を患者に投与する場合には、錠剤、カプセル剤、散剤、顆粒剤、軟膏剤、注射剤等の剤形が適宜選択されるが、製剤化に当たってはそれぞれの剤形に応じて種々の工夫がなされる。例えば、経口的に薬剤を投与することが困難な患者に対する投与ルートの一つとして経皮投与が知られているが、一般に、塩形の薬物は皮膚に対する透過性が悪いため経皮製剤中に薬物を配合するためには遊離型とする場合が多い。
【０００３】
【発明が解決しようとする課題】
抗痴呆薬、特にドネペジルは製剤化した場合に光に対して不安定である。そこで本発明者は光に対する安定性を増大させるべく鋭意検討した結果、以下の手段により課題を解決できることを見い出し本発明を完成した。
【０００４】
【課題を解決するための手段】
本発明は、ドネペジル及び有機酸からなる光安定化した抗痴呆薬組成物である。また、本発明は、ドネペジルに有機酸を添加することによる抗痴呆薬の光安定化方法である。本発明における抗痴呆薬の具体例としては、ドネペジルを挙げることができる。ドネペジルは、通常塩酸ドネペジルとして、軽度〜中等度のアルツハイマー症痴呆治療剤として用いられている。化学名は、１−ベンジルー４−（５，６−ジメトキシインダノンー２−イル）メチルピペリジンである。この構造式及び抗痴呆薬であるＴＡＫ−１４７、ＣＰ１１８９５４等の構造式は、以下に示すとおりである。
【０００５】
【化１】
本発明における有機酸は特に限定されず、例えばトシル酸、メシル酸、安息香酸、サリチル酸、酒石酸、クエン酸、フマル酸、マレイン酸又はステアリン酸等の高級脂肪酸等を挙げることができるが、特にメシル酸、サリチル酸及びクエン酸が好ましい。有機酸は、1種のみでも2種以上を混合して用いてもよい。
ドネペジルと有機酸の比率は、特に限定されないが、通常ドネペジル1重量部に対して有機酸0.1〜10重量部であり、好ましくは0.2〜5重量部、より好ましくは0.2〜2重量部である。
【０００７】
本発明における組成物は、錠剤、顆粒剤、散剤、軟膏剤、注射剤等の剤形として使用することができる。それそれの剤形とするには、従来知られている方法によることができる。例えば、顆粒剤の場合は、抗痴呆薬を乳糖、マンニトール、コーンスターチ、結晶セルロース等の賦形剤と混合し、ヒドロキシプロピルセルロース、ポリビニルピロリドン等の結合剤を水等の溶媒に溶解して添加、混練合し、押出し造粒機等により製造することができる。また軟膏剤の場合は、流動パラフィン、硬化油、植物油、スクワラン、高級アルコール類、高級脂肪酸、高級脂肪酸のエステル、グリセリン、水、防腐剤、色素等のいわゆる軟膏基剤とともに使用することができ、通常用いられる方法により製造することができる。
【０００８】
【発明の効果】
本発明よると、ドネペジルの光に対する安定性が顕著に増大する。以下に具体例を挙げて本発明の効果を示す。
ドネペジル濃度が1mg/mLのエタノール・水（１：１）溶液を調整し、この溶液にトシル酸、メシル酸、安息香酸、サリチル酸、酒石酸及びクエン酸をドネペジルと等モルになるように添加後、その５ｍＬを透明なガラスアンプルに封入した。ｐＨはそれぞれ、5.74、5.84、5.73、5.89、5.75及び3.28であった。なお、有機酸を添加しない場合のｐＨは、5.63であった。このガラスアンプルを室温1000Luxで1ヶ月間保存し含量を測定した。別に、冷所に1ヶ月保存したものの含量を測定し、光照射下における残存率を求めた。含量の測定は、高速液体クロマトグラフィーを用いた。結果を表１に示した。
【０００９】
【表１】
表１に示したように本発明にかかる組成物は、何も添加しない試料と比較して著しく安定性が増大した。特に、メシル酸、サリチル酸及びクエン酸はクロマトグラム上分解物のピークが認められず、ほとんど分解していないものと考えられた。
軟膏等の経皮製剤は皮膚に塗布後、光にさらされる場合が多いため、本発明に係る組成物は特に有用である。
【００１１】
【実施例】
以下に実施例を挙げて本発明を更に詳細に説明するが、本発明がこれらに限定されるわけではない。
【００１２】
実施例１
ドネペジル５ｇ、トシル酸５ｇ、乳糖１５０ｇ、マンニトール２００ｇ及び低置換度ヒドロキシプロピルセルロース２０ｇを混合し、水５０ｍｌに溶解したヒドロキシプロピルセルロース７ｇを徐々に加えながら混練合した。この練合物を押出し造粒機に投入し、顆粒剤を製造した。スクリーンは0.4mmとした。
【００１３】
実施例２
ドネペジル５００ｍｇ、クエン酸２００ｍｇ及びグルコース２０００ｍｇを注射用蒸留水に溶解し、0.1N水酸化ナトリウムによりｐＨを5.5に調整後、さらに注射用蒸留水を加えて１００ｍｌとした。アンプルに１ｍｌずつ分注し、溶閉後１２１℃で１５分間滅菌して注射剤を製造した。[0001]
[Industrial application fields]
The present invention relates to an anti-dementia drug, and in particular to donepezil photostabilization composition and donepezil photostabilization method.
[0002]
BACKGROUND OF THE INVENTION AND PRIOR ART
In recent years, care for senile dementia has become a social problem, and the development of therapeutic drugs has been actively conducted. Among them, donepezil is highly evaluated as a therapeutic agent for mild to moderate Alzheimer's dementia having an acetylcholinesterase inhibitory action. Donepezil is a basic drug and is usually provided as a hydrochloride salt.
On the other hand, when a drug is administered to a patient, dosage forms such as tablets, capsules, powders, granules, ointments, injections, etc. are appropriately selected. Is devised. For example, transdermal administration is known as one of the administration routes for patients who are difficult to administer drugs orally, but in general, salt-form drugs are poorly permeable to the skin, so they are used in transdermal formulations. In many cases, a free form is used to add a drug.
[0003]
[Problems to be solved by the invention]
Anti-dementia drugs, especially donepezil, are unstable to light when formulated. Thus, as a result of intensive studies to increase the stability to light, the present inventor has found that the problems can be solved by the following means and completed the present invention.
[0004]
[Means for Solving the Problems]
The present invention is a photostabilized anti-dementia drug composition comprising donepezil and an organic acid. The present invention is also a method for photostabilizing an anti-dementia drug by adding an organic acid to donepezil. Specific examples of the anti-dementia drug in the present invention include donepezil. Donepezil is usually used as donepezil hydrochloride as a therapeutic agent for mild to moderate dementia of Alzheimer's disease. The chemical name is 1-benzyl-4- (5,6-dimethoxyindanone-2-yl) methylpiperidine. This structural formula and structural formulas such as TAK-147 and CP118954 which are anti-dementia drugs are as follows.
[0005]
[Chemical 1]
The organic acid in the present invention is not particularly limited, and examples thereof include higher fatty acids such as tosylic acid, mesylic acid, benzoic acid, salicylic acid, tartaric acid, citric acid, fumaric acid, maleic acid and stearic acid. Acid, salicylic acid and citric acid are preferred. The organic acid may be used alone or in combination of two or more.
The ratio of donepezil and the organic acid is not particularly limited, but is usually 0.1 to 10 parts by weight, preferably 0.2 to 5 parts by weight, more preferably 0.2 to 2 parts by weight with respect to 1 part by weight of donepezil.
[0007]
The composition in this invention can be used as dosage forms, such as a tablet, a granule, a powder, an ointment, an injection. The dosage form can be obtained by a conventionally known method. For example, in the case of granules, an anti-dementia drug is mixed with excipients such as lactose, mannitol, corn starch, and crystalline cellulose, and a binder such as hydroxypropylcellulose and polyvinylpyrrolidone is dissolved in a solvent such as water and added, They can be kneaded and manufactured by an extrusion granulator or the like. In the case of an ointment, it can be used with so-called ointment bases such as liquid paraffin, hydrogenated oil, vegetable oil, squalane, higher alcohols, higher fatty acids, esters of higher fatty acids, glycerin, water, preservatives, pigments, It can be produced by a commonly used method.
[0008]
【The invention's effect】
According to the present invention, the stability of donepezil to light is significantly increased. The effect of this invention is shown by giving a specific example below.
After adjusting the ethanol / water (1: 1) solution with a donepezil concentration of 1 mg / mL, tosylic acid, mesylic acid, benzoic acid, salicylic acid, tartaric acid and citric acid were added to this solution so as to be equimolar with donepezil, 5 mL thereof was sealed in a transparent glass ampoule. The pH was 5.74, 5.84, 5.73, 5.89, 5.75 and 3.28, respectively. The pH when no organic acid was added was 5.63. The glass ampule was stored at a room temperature of 1000 Lux for 1 month and the content was measured. Separately, the content of those stored for 1 month in a cold place was measured, and the residual rate under light irradiation was determined. The content was measured using high performance liquid chromatography. The results are shown in Table 1.
[0009]
[Table 1]
As shown in Table 1, the stability of the composition according to the present invention was remarkably increased as compared with the sample to which nothing was added. In particular, mesylic acid, salicylic acid, and citric acid were considered to have almost no decomposition because no peaks of decomposition products were observed on the chromatogram.
Since transdermal preparations such as ointments are often exposed to light after being applied to the skin, the composition according to the present invention is particularly useful.
[0011]
【Example】
The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
[0012]
Example 1
Donepezil 5 g, tosylic acid 5 g, lactose 150 g, mannitol 200 g and low-substituted hydroxypropylcellulose 20 g were mixed and kneaded while gradually adding 7 g of hydroxypropylcellulose dissolved in 50 ml of water. This kneaded product was put into an extrusion granulator to produce granules. The screen was 0.4 mm.
[0013]
Example 2
Donepezil 500 mg, citric acid 200 mg, and glucose 2000 mg were dissolved in distilled water for injection, the pH was adjusted to 5.5 with 0.1N sodium hydroxide, and distilled water for injection was further added to make 100 ml. 1 ml of aliquot was dispensed into ampoules, and sterilized at 121 ° C. for 15 minutes after melt-sealing to produce an injection.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26874797A JP3797764B2 (en) | 1997-10-01 | 1997-10-01 | Light stabilizing composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26874797A JP3797764B2 (en) | 1997-10-01 | 1997-10-01 | Light stabilizing composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH11106353A JPH11106353A (en) | 1999-04-20 |
| JP3797764B2 true JP3797764B2 (en) | 2006-07-19 |
Family
ID=17462783
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP26874797A Expired - Fee Related JP3797764B2 (en) | 1997-10-01 | 1997-10-01 | Light stabilizing composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3797764B2 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2273409T3 (en) | 1997-03-28 | 2007-05-01 | Eisai Co., Ltd. | ORAL MEDICINES THAT PREVENT UNFORGETTABLE AND SIMILAR FLAVOR. |
| ATE254928T1 (en) * | 1999-03-31 | 2003-12-15 | Eisai Co Ltd | STABILIZED COMPOSITION WITH NOOTROPIC ACTIVE INGREDIENTS |
| PT1260215E (en) | 2000-03-01 | 2009-09-03 | Eisai R&D Man Co Ltd | Rapidly disintegrable tablet containing polyvinyl alcohol |
| WO2005065645A2 (en) * | 2003-12-31 | 2005-07-21 | Actavis Group Hf | Donepezil formulations |
| MX2007007836A (en) * | 2004-12-27 | 2007-08-20 | Eisai R&D Man Co Ltd | Method for stabilizing anti-dementia drug. |
| US20090208579A1 (en) * | 2004-12-27 | 2009-08-20 | Eisai R & D Management Co., Ltd. | Matrix Type Sustained-Release Preparation Containing Basic Drug or Salt Thereof, and Method for Manufacturing the Same |
| JP4953650B2 (en) * | 2005-02-09 | 2012-06-13 | ロート製薬株式会社 | Planoprofen-containing composition |
| JP5275560B2 (en) * | 2006-10-24 | 2013-08-28 | 小林化工株式会社 | Method for producing uncoated tablets containing zolpidem tartrate |
| EP2127651A4 (en) | 2007-01-19 | 2012-08-01 | Eisai R&D Man Co Ltd | Stabilized medicinal composition containing donepezil, method of producing the same and method for stabilization |
| CN101450049A (en) | 2007-12-07 | 2009-06-10 | 辉凌国际制药（瑞士）有限公司 | Pharmaceutical composition |
| PL2898886T3 (en) * | 2012-09-19 | 2017-06-30 | Taiho Pharmaceutical Co., Ltd. | Pharmaceutical composition for oral administration with improved elution and/or absorbency |
-
1997
- 1997-10-01 JP JP26874797A patent/JP3797764B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH11106353A (en) | 1999-04-20 |
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