JP5138345B2 - 抗アレルギー剤 - Google Patents
抗アレルギー剤 Download PDFInfo
- Publication number
- JP5138345B2 JP5138345B2 JP2007298732A JP2007298732A JP5138345B2 JP 5138345 B2 JP5138345 B2 JP 5138345B2 JP 2007298732 A JP2007298732 A JP 2007298732A JP 2007298732 A JP2007298732 A JP 2007298732A JP 5138345 B2 JP5138345 B2 JP 5138345B2
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- JP
- Japan
- Prior art keywords
- compound
- formulation
- antiallergic agent
- antiallergic
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
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- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
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- 229940054441 o-phthalaldehyde Drugs 0.000 description 1
- 229940073665 octyldodecyl myristate Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 201000004338 pollen allergy Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
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- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 235000019423 pullulan Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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- 235000009566 rice Nutrition 0.000 description 1
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- OVVGHDNPYGTYIT-BNXXONSGSA-N rutinose Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 OVVGHDNPYGTYIT-BNXXONSGSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
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Landscapes
- Saccharide Compounds (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
化合物(2)はオリーブ葉熱水抽出物(オピエース タマ生化学社製)から精製した。すなわち、オリーブ葉熱水抽出物1.5kgをイオン交換水10Lに懸濁し、2L×5回の酢酸エチルを用いて分配し、酢酸エチル層を凍結乾燥することで酢酸エチル画分を得た。該酢酸エチル画分を30%(v/v)メタノールに溶解し、sephadex LH−20(Pharmacia Biotech社製)を充填したカラムに添加し、60%(v/v)メタノールにて溶出し、LH−20分画物を得た。該分画物を、該凍結乾燥品をオクタデシル化シリカゲルにより精製し、濃縮乾固した後、凍結乾燥して化合物(2)316mgを得た。
化合物(2)100mgを水100mLに溶解し、0.1N水酸化ナトリウムを5mL添加した後、凍結乾燥してナトリウム塩87mgを得た。
処方 配合量(%)
1.化合物(2)(製造例1) 2.0
2.砂糖 78.8
3.グルコース 19.0
4.ショ糖脂肪酸エステル 0.2
<製法>
成分1〜3に70%エタノールを適量加えて練和し、押出し造粒した後に乾燥して顆粒を得る。成分4を加えて打錠成形し、1gの錠菓を得る。当該錠菓を1日4錠摂取することで、化合物(2)を80mg/日摂取できる。
処方 配合量(%)
1.化合物(2)(製造例1) 1.0
2.マルチトール 70.0
3.デンプン糖化物 29.0
<製法>
成分1〜3を120〜170℃で加熱溶解し、金型にて固化させ、3gの飴を得る。当該飴を1日3個摂取することで、化合物(2)を90mg/日摂取できる。
処方例2において化合物(2)(製造例1)をデンプン糖化物に置き換えたものを従来のキャンディーとした。
処方 配合量(%)
1.化合物(2)(製造例1) 4.0
2.乳糖 81.0
3.セルロース 15.0
<製法>
成分1〜3に70%エタノールを適量加えて練和して押出し造粒し、乾燥して顆粒剤を得る。当該顆粒剤は、1回1gずつ1日3回摂取することで、化合物(2)のナトリウム塩を120mg/日摂取できる。
処方 配合量(%)
1.化合物(2)(製造例1) 0.2
2.ショ糖 6.0
3.クエン酸 0.75
4.香料 適量
5.精製水にて全量を100とする。
<製法>
成分5に成分1〜4を加え、撹拌溶解して濾過し、加熱殺菌して100gとし、これを50gガラス瓶に充填する。当該飲料は、1日1本摂取することで化合物(2)を100mg/日摂取できる。
処方 配合量(%)
1. 化合物(2)(製造例1) 0.1
2. 1,3−ブチレングリコール 8.0
3. グリセリン 2.0
4. キサンタンガム 0.02
5. クエン酸 0.01
6. クエン酸ナトリウム 0.1
7. エタノール 5.0
8. パラオキシ安息香酸メチル 0.1
9. ポリオキシエチレン硬化ヒマシ油(40E.O.) 0.1
10.香料 適量
11.精製水にて全量を100とする
<製法>
成分1〜6及び11と、成分7〜10をそれぞれ均一に溶解し、両者を混合し、濾過して製品とする。
処方例5において化合物(2)(製造例1)を精製水に置き換えたものを従来の化粧水とした。
処方 配合量(%)
1. 化合物(2)(製造例1) 0.05
2. スクワラン 5.5
3. オリーブ油 3.0
4. ステアリン酸 2.0
5. ミツロウ 2.0
6. ミリスチン酸オクチルドデシル 3.5
7. ポリオキシエチレンセチルエーテル(20E.O.) 3.0
8. ベヘニルアルコール 1.5
9. モノステアリン酸グリセリン 2.5
10.香料 適量
11.パラオキシ安息香酸メチル 0.2
12.パラオキシ安息香酸エチル 0.05
13.1,3−ブチレングリコール 8.5
14.精製水にて全量を100とする
<製法>
成分2〜9を加熱溶解して混合し、70℃に保ち油相とする。成分1及び11〜14を加熱溶解して混合し、75℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、45℃で成分10を加え、更に30℃まで冷却して製品とする。
処方 配合量(%)
1. 化合物(2)(製造例1) 0.5
2. スクワラン 5.0
3. オリーブ油 5.0
4. ホホバ油 5.0
5. セタノール 1.5
6. モノステアリン酸グリセリン 2.0
7. ポリオキシエチレンセチルエーテル(20E.O.) 3.0
8. ポリオキシエチレンソルビタンモノオレエート
(20E.O.) 2.0
9. 香料 適量
10.プロピレングリコール 1.0
11.グリセリン 2.0
12.パラオキシ安息香酸メチル 0.2
13.精製水にて全量を100とする
<製法>
成分2〜8を加熱溶解して混合し、70℃に保ち油相とする。成分1および10〜13を加熱溶解して混合し、75℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、45℃で成分9を加え、さらに30℃まで冷却して製品とする。
処方 配合量(%)
1. 化合物(2)(製造例1) 1.0
2. エタノール 5.0
3. パラオキシ安息香酸メチル 0.1
4. ポリオキシエチレン硬化ヒマシ油(60E.O.) 0.1
5. 香料 適量
6. 1,3−ブチレングリコール 5.0
7. グリセリン 5.0
8. キサンタンガム 0.1
9. カルボキシビニルポリマー 0.2
10.水酸化カリウム 0.2
11.精製水にて全量を100とする
<製法>
成分2〜5と、成分1及び6〜11をそれぞれ均一に溶解し、両者を混合して製品とする。
処方 配合量(%)
1. 化合物(2)(製造例1) 1.0
2. ステアリン酸 2.4
3. ポリオキシエチレンソルビタンモノステアレート
(20E.O.) 1.0
4. ポリオキシエチレンセチルエーテル(20E.O.) 2.0
5. セタノール 1.0
6. 液状ラノリン 2.0
7. 流動パラフィン 3.0
8. ミリスチン酸イソプロピル 6.5
9. カルボキシメチルセルロースナトリウム 0.1
10.ベントナイト 0.5
11.プロピレングリコール 4.0
12.トリエタノールアミン 1.1
13.パラオキシ安息香酸メチル 0.2
14.二酸化チタン 8.0
15.タルク 4.0
16.ベンガラ 1.0
17.黄酸化鉄 2.0
18.香料 適量
19.精製水にて全量を100とする
<製法>
成分2〜8を加熱溶解し、80℃に保ち油相とする。成分19に成分9をよく膨潤させ、続いて、成分1及び10〜13を加えて均一に混合する。これに粉砕機で粉砕混合した成分14〜17を加え、ホモミキサーで撹拌し75℃に保ち水相とする。この水相に油相をかき混ぜながら加え、冷却し、45℃で成分18を加え、かき混ぜながら30℃まで冷却して製品とする。
処方 配合量(%)
1.化合物(2)(製造例1) 1.0
2.エタノール 63.0
3.グリセリン 2.0
4.精製水にて全量を100とする
<製法>
成分1〜3を成分4に溶解し、製品とする。
処方 配合量(%)
1.化合物(2)のナトリウム塩(製造例2) 1.0
2.炭酸水素ナトリウム 50.0
3.黄色202号(1) 適量
4.香料 適量
5.硫酸ナトリウムにて全量を100とする
<製法>
成分1〜5を均一に混合し、製品とする。
Wister系雄性ラット(8週齢)腹腔から採取した肥満細胞浮遊液を2×105個/mLとなるように調整し、その650μLにIgE抗体を含むラット血清の8倍希釈液320μLを加え、37℃で30分インキュベートした。次に、化合物(2)(製造例1)を1.0mg/mLとなるように加え、37℃で10分間インキュベートした。さらに、卵白アルブミン20μg及びフォスファチジルセリン30μgを加え、37℃で20分間インキュベートして抗原刺激を行った後、肥満細胞浮遊液を4℃に冷却し、反応を停止させた。十分に冷却した後、3,000回転で5分間遠心分離し、遊離したヒスタミンを含む上清を回収した。
上清のヒスタミンは、n−ヘプタン中で塩酸を加えてヒスタミン塩酸塩とした後、o−フタルアルデヒド法により、蛍光強度を測定することにより定量した。
花粉症の自覚症状を持つ被験者30名に、処方例2に記載のキャンディーを1日当たり3個、1ヶ月にわたり摂取させ、摂取前後の花粉症の症状についてアンケートを実施し、改善効果を検討した。なお、比較処方例1記載の従来のキャンディーについてもプラセボ群として上記の被験者30名のうち15名に試験を実施した。
アトピー性皮膚炎の自覚症状を持つ被験者20名に、処方例5記載の化粧水を1日当たり3回、1ヶ月にわたり塗布させ、塗布前後のアトピー性皮膚炎の症状についてアンケートを実施し、改善効果を検討した。なお、比較処方例2記載の従来の化粧水についてもプラセボ群として上記の被験者20名のうち10名に試験を実施した。
Claims (5)
- 抗アレルギー効果がヒスタミン遊離抑制効果であることを特徴とする請求項1記載の抗アレルギー剤。
- 請求項1又は2記載の抗アレルギー剤を含有し、1日の投与量が体重1kg当たり一般式(2)で表される化合物として0.01mg〜10mgであることを特徴とする花粉症改善剤。
- 請求項1又は2記載の抗アレルギー剤を含有し、1日の投与量が体重1kg当たり一般式(2)で表される化合物として0.01mg〜10mgであることを特徴とするアトピー性皮膚炎改善剤。
- 請求項1又は2いずれか記載の抗アレルギー剤を0.01〜10重量%含有することを特徴とする化粧品。
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