JP2009298800A - 抗ウイルス剤組成物 - Google Patents
抗ウイルス剤組成物 Download PDFInfo
- Publication number
- JP2009298800A JP2009298800A JP2009187888A JP2009187888A JP2009298800A JP 2009298800 A JP2009298800 A JP 2009298800A JP 2009187888 A JP2009187888 A JP 2009187888A JP 2009187888 A JP2009187888 A JP 2009187888A JP 2009298800 A JP2009298800 A JP 2009298800A
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- Prior art keywords
- composition
- present
- arginine
- cancer
- zinc
- 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
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Abstract
【解決手段】治療学的有効量のクエン酸および/または亜鉛及びL−アルギニンを、薬剤学的に許容可能な担体とともに含有し、抗癌剤の強い毒性により正常細胞に深刻な損傷を被るなどの副作用がなく、優れた抗癌効果または抗ウイルス効果を示す、抗癌剤組成物、または抗ウイルス剤組成物。
【選択図】なし
Description
クエン酸(Sigma, U.S.A.)、亜鉛(Sigma, U.S.A.)およびL−アルギニン(Sigma, U.S.A.)を、下記の表2に記載の本発明の組成物による活性成分を選んで配合した後、滅菌水を100%の組成量として、それぞれの活性成分とともに混合した後、これをバイアル(100mg)に充填して本発明の組成物を製造した。
クエン酸(Sigma, U.S.A.)、亜鉛(Sigma, U.S.A.)およびL−アルギニン(Sigma, U.S.A.)を上記の表2による活性成分を選んで配合した後、ラクトース30重量%、ステアリン酸マグネシウム5重量%、グリコール酸澱粉ナトリウム10重量%、および滅菌水を100%の組成量として、それぞれの活性成分とともに混合した後、これを30〜60℃に維持しながら、1時間の間攪拌して室温で冷却させた後、通常の錠剤の製造方法により打錠して組成物350mgずつを含有する錠剤を製造した。
本発明の組成物のうち抗ウイルス剤組成物を経皮剤形に製造するために、クエン酸2重量%、亜鉛0.1重量%およびL−アルギニン5重量%を、1Lのエタノールが満たされたビーカーに溶解させた後、−20℃で24時間冷凍保管した。その後、前記ビーカーで凝固物を得て、これを経皮剤形の活性成分として用いた。前記凝固物は、約10倍の濃縮率を有する。
油相
ステアリン酸 13重量%
ステアリルアルコール 1重量%
エチルアルコール 1重量%
製造された凝固物 5重量%
水相
グリセリン 10重量%
メチルパラベン 0.1重量%
プロピルパラベン 0.05重量%
水酸化カリウム 0.9重量%
蒸留水 100%組成量
油相と水相を別途に65℃に加熱し、油相を水相に徐々に加えながら攪拌させることによって粗エマルジョンを形成した。形成されたエマルジョンを約50℃に冷却させて均質化した。均質化物が凝結するまで振盪させながら冷却させることによって、クリーム剤を得た。
ワセリン 80重量%
ステアリルアルコール 3重量%
白蝋 9重量%
コレステロール 3重量%
製造された凝固物 5重量%
ステアリルアルコール、白蝋、コレステロールおよび前記製造された凝固物をスチームバスで溶かし、ワセリンを添加した後、液体が形成するまで徐々に加熱し続けた。攪拌冷却させて凝結することにより、軟膏剤を得た。
メトセル90H.C.4000 0.8重量%
カルボポル934 0.24重量%
プロピレングリコール 16.7重量%
メチルパラベン 0.015重量%
製造された凝固物 5重量%
水酸化ナトリウム pH7調整量
蒸留水 100%組成量
メトセルを熱水(80〜90℃)に分散させ、一夜冷蔵庫で冷却させて溶液化した。カルボポル934、前記凝固物を水に分散させ、分散液に十分な量の水酸化ナトリウム溶液を添加して、pHを7.0に調節した。蒸留水を添加して容量を40mlとした。メチルパラベンをプロピレングリコール中に溶解させた。メトセル、カルボポル934およびプロピレングリコールを混合してゲルを得た。
酸化亜鉛 25重量%
澱粉 25重量%
カラミン 5重量%
製造された凝固物 5重量%
ワセリン 100%組成量
カラミンを酸化亜鉛、前記凝固物および澱粉で滴定し、乳鉢で粉末化してワセリンに均一に入れてペースト剤を得た。
クエン酸とL−アルギニンを活性成分として含有した本発明の抗癌剤組成物が、癌細胞の成長と生存に及ぼす影響を調べるために、クエン酸とL−アルギニンの含量を異にして製造した組成物(表3)を癌細胞株に処理して、細胞生存率を測定した。細胞株としては、SKOV−3(ヒト卵巣腺腫(複数)、ATCC番号:HTB−77)とU87(ヒト神経膠芽腫細胞、ATCC番号:HTB−14)を用いた。
亜鉛とL−アルギニンを活性成分として含有した本発明の抗癌剤組成物が、癌細胞の成長と生存に及ぼす影響を調べるために、亜鉛とL−アルギニンの含量を異にして製造した組成物(表4)を癌細胞株に処理して、細胞生存率を測定した。細胞株としては、SKOV−3とU87を用いた。これらの細胞の培養、前記組成物を癌細胞株に処理する方法、および細胞生存率の測定は、前記実施例4と同様の方法により行った。図2に実験の結果を示した。
クエン酸、亜鉛およびL−アルギニンを活性成分として含有した本発明の抗癌剤組成物が、癌細胞の成長と生存に及ぼす影響を調べるために、クエン酸、亜鉛およびL−アルギニンの含量を異にして製造した組成物(表5)を癌細胞株に処理して、細胞生存率を測定した。細胞株としては、SKOV−3、NIH:OVCAR−3(ヒト卵巣腺腫、ATCC番号:HTB−161)およびNOSE(ヒト卵巣表面正常上皮細胞)を用いた。これらの細胞の培養、前記組成物を癌細胞株に処理する方法、および細胞生存率の測定は、前記実施例4と同様の方法により行った。図3に実験の結果を示した。
クエン酸、亜鉛およびL−アルギニンを活性成分として含有した本発明の抗癌剤組成物が、癌細胞の成長と生存に及ぼす影響を調べるために、クエン酸、亜鉛およびL−アルギニンの含量を異にして実施例5で製造した組成物(表5)を癌細胞株に処理して、細胞生存率を測定した。細胞株としては、ヒト子宮頸部癌細胞であるCa Ski(ATCC番号:CRL−1550)、HeLa(ATCC番号:CCL−2)およびC−33 A(ATCC番号:HTB−31)を用いた。これらの細胞の培養、前記組成物を癌細胞株に処理する方法、および細胞生存率の測定は、前記実施例4と同様の方法により行った。図4に実験の結果を示した。
実施例1で製造した本発明の抗癌剤組成物が細胞内DNA分裂に及ぼす影響をフローサイトメトリーにより分析した。
前記実施例8の細胞死滅の機序を調査するためにDNAラダリング分析を行った。CaSki、HeLaおよびC−33 A細胞株をそれぞれ2×106細胞/ウェルとなるように96−ウェルプレートに入れた後、実施例1で製造した本発明の抗癌剤組成物(表1の組成物3)100mlを前記細胞株にそれぞれ処理して、6時間、12時間、24時間および48時間の間、実施例4と同様の方法で培養した後、経時的に培養したそれぞれの細胞を回収して、細胞のDNAを公知の方法により次のように変形して抽出した(Leszczynski D. et. al. Photochem. Photobiol., 1996, Vol.64, p936-.)。前記それぞれの細胞プレートを、SDS(ドデシル硫酸ナトリウム)0.5%、EDTA(エチレンジアミン四酢酸)2mM、蛋白質加水分解酵素K100mg/ml、およびトリス塩酸緩衝液50mM(pH8.0)で構成された溶解緩衝液に懸濁させた。これを55℃で3時間培養し、培養液と同量でフェノール:クロロホルム:イソアミルアルコール(25:24:1)を添加した。これに培養液の0.1体積%の酢酸アンモニウムと2.5体積%の冷たい無水エタノールを添加してDNAを沈殿させ、−20℃で一夜間保管した。前記DNAをTE(1Mトリス塩酸緩衝液のうち0.5M EDTA、pH8.0)に溶解させ、37℃でRNase A 100mg/mlを添加して1時間培養した。前記試料を臭化エチジウム0.5μg/mlが含まれた1.5%アガロスゲルで60Vで1時間の間電気泳動し、紫外線(UV)に露出させた。図8に実験の結果を示した。
癌細胞の細胞死滅の機序を調査するために、細胞死滅と関連した蛋白質であるP53とP21、および癌誘発蛋白質であるC−Mycの発現を分析した。
前記実施例8の細胞死滅の機序を調べるために、本発明の抗癌剤組成物で処理された細胞の染色された核を観察した。
本発明の抗ウイルス剤組成物が子宮癌細胞株において発現するパピローマウイルスの蛋白質を減少させるのかについて調べるために、発癌蛋白質であるヒトパピローマウイルス16型または18型のE6とE7の発現を分析した。
外陰部に尖圭コンジローマが生じた6名の女性患者を対象として実施例3で製造した軟膏剤(実施例3の経皮剤(2))1gをそれぞれの患部に塗った。その結果、これらの患者は、1日2回適用することにより、病変の大きさに応じて2〜12週間以内に治療された。これを図14に示した。
本発明の抗ウイルス剤組成物がウイルス増殖を抑制させることを証明するために、エンテロウイルスとポリオウイルスにそれぞれ感染した細胞に本発明の抗ウイルス剤組成物を処理して細胞病変を分析した。
Claims (4)
- 治療学的有効量のクエン酸および/または亜鉛およびL−アルギニンを薬剤学的に許容可能な担体とともに含有し、ウイルスの蛋白質発現の減少を誘導することを特徴とする抗ウイルス剤組成物。
- 前記抗ウイルス剤組成物が、前記組成物の総重量に対し、0.001〜20重量%のクエン酸、および/または0.0001〜5重量%の亜鉛、および0.001〜20重量%のL−アルギニンを含有することを特徴とする請求項1に記載の抗ウイルス剤組成物。
- 前記抗ウイルス剤組成物の適用対象が、パピローマウイルス;エイズウイルス;エンテロウイルス;ポリオウイルスからなる群から選択されることを特徴とする請求項1または2に記載の抗ウイルス剤組成物。
- 前記抗ウイルス剤組成物の剤形が、経口投与用抗ウイルス剤、非経口投与用抗ウイルス剤、クリーム剤、軟膏剤、ゲル剤またはペースト剤からなる群から選択されることを特徴とする請求項1乃至3のいずれか一つに記載の抗ウイルス剤組成物。
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WO2012105595A1 (ja) | 2011-02-02 | 2012-08-09 | 公益財団法人微生物化学研究会 | 血液脳関門を透過する薬物輸送体、ペプチド及びその用途 |
JP2018117617A (ja) * | 2010-12-24 | 2018-08-02 | エヌ.ブイ.・ヌートリシア | 改良型栄養タブレット |
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US7968122B2 (en) | 2003-12-10 | 2011-06-28 | Adventrx Pharmaceuticals, Inc. | Anti-viral pharmaceutical compositions |
KR100656807B1 (ko) * | 2005-02-23 | 2006-12-13 | 배석년 | 구연산, 아연 및 아르기닌으로 이루어진 팽창선조 예방 및치료용 조성물 |
WO2008111429A1 (ja) * | 2007-03-09 | 2008-09-18 | Maruishi Pharmaceutical Co., Ltd. | 消毒剤 |
KR101546802B1 (ko) * | 2013-06-12 | 2015-08-24 | 박래옥 | 붕산, 구연산, 아연, 알부민 및 비타민 c를 포함하는 파필로마 바이러스에 대한 항바이러스 피부외용제 조성물 |
WO2019000163A1 (zh) * | 2017-06-26 | 2019-01-03 | 余祖江 | 精氨酸在制备抗肿瘤药物中的用途 |
KR102664243B1 (ko) * | 2018-01-19 | 2024-05-08 | 데루타-후라이 화마 가부시키가이샤 | 암 환자의 치료에 유용한 오줌의 알칼리제 |
KR102155802B1 (ko) * | 2018-09-21 | 2020-09-14 | 박래옥 | 시트르산 및 아르기닌 포함 아연 착화합물 |
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