JPH11508606A - 経口用ペプチド薬剤 - Google Patents
経口用ペプチド薬剤Info
- Publication number
- JPH11508606A JPH11508606A JP9532859A JP53285997A JPH11508606A JP H11508606 A JPH11508606 A JP H11508606A JP 9532859 A JP9532859 A JP 9532859A JP 53285997 A JP53285997 A JP 53285997A JP H11508606 A JPH11508606 A JP H11508606A
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- lowering agent
- peptide
- agent
- salmon calcitonin
- 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
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.生理的活性ペプチド剤の経口用の医薬組成物であって、 (A)治療上効果的な量の該活性ペプチド剤; (B)少なくとも1種の薬学的に許容されるpH低下剤; (C)該活性剤のバイオアベイラビリティを促進するのに効果的な少なくとも 1種の吸収増進剤; (D)該活性ペプチドと胃プロテアーゼとの接触を防止する間、患者の胃を通 して該医薬組成物を移送するのに効果的な酸抵抗性保護運搬剤; (うち、pH低下剤は、該組成物を 0.1M炭酸水素ナトリウム水溶液10mlに 加えたときに、該溶液のpHを5.5以下にするのに十分となる量で、該医薬組成 物中に存在する) を含む医薬組成物。 2.該医薬組成物が 0.1M 炭酸水素ナトリウム水溶液10mlの量に加えられときに 該水溶液のpHを 3.5以下にするのに十分な量で、該pH低下剤が存在する、請 求項1の医薬組成物。 3.該保護運搬剤が該医薬組成物の残余の重量に対して30%以下の重量で存在 する、請求項1の医薬組成物。 4.該腸溶コーティングが該医薬組成物の残余の重量に対して20%以下の重量 で存在する、請求項1の医薬組成物。 5.該腸溶コーティングが該医薬組成物の残余の重量に対して10%−20%の 重量で存在する、請求項1の医薬組成物。 6.該保護運搬剤が、0.1N HCl 中で少なくとも2時間、該医薬組成物の分解を 防止し、該組成物を1分間100回転する分解浴でpHを6.3まで増加した後、 30分以内に該医薬組成物の全成分を完全に放出し得るのに十分である、請求項 1の医薬組成物。 7.該吸収増進剤が界面活性剤である、請求項1の医薬組成物。 8.該界面活性剤が吸収性または生分解性である、請求項1の医薬組成物。 9.該界面活性剤がアシルカルニチン、ホスホリピドおよび胆汁酸よりなる群か ら選ばれる、請求項8の医薬組成物。 10.該増進剤がアシルカルニチンである、請求項9の医薬組成物。 11.さらにスクロースエステルを含有する、請求項10の医薬組成物。 12.該吸収増進剤が(i)コレステロール誘導体であるアニオン界面活性剤、( ii)負電荷中和剤とアニオン界面活性剤との混合物、(iii)非イオン界面活性剤、 および(iv)カチオン界面活性剤よりなる群から選ばれる界面活性剤である、請求 項1の医薬組成物。 13.該吸収増進剤がカチオン界面活性剤およびコレステロール誘導体であるア ニオン界面活性剤よりなる群から選ばれる、請求項1の医薬組成物。 14.該医薬組成物が少なくとも2種の吸収増進剤を含有し、その一つがカチオ ン界面活性剤であり、他の一つがコレステロール誘導体であるアニオン界面活性 剤である、請求項1の医薬組成物。 15.該アニオン界面活性剤が酸溶解性胆汁酸である、請求項14の医薬組成物 。 16.さらに該ペプチド活性剤のバイオアベイラビリティを高めるのに効果的な 量の第二ペプチドを含む、請求項1の医薬組成物。 17.さらに該pH低下剤を該保護運搬剤から分離する水溶性障壁を含む、請求 項1の医薬組成物。 18.該医薬組成物が 4.2 以下のpKaを有する少なくとも1種のpH低下剤 を含有する、請求項1の医薬組成物。 19.少なくとも1種のpH低下剤が室温で水100mlに対し少なくとも30 gの水溶性を有する、請求項1の医薬組成物。 20.該腸溶コーティング以外の全成分が均一に分散している、請求項1の医薬 組成物。 21.該医薬組成物が医薬バインダー含有の顆粒を含み、該バインダー中に該p H低下剤、該吸収増進剤および該ペプチド活性剤が均一に分散している、請求項 20の医薬組成物。 22.該医薬組成物が該吸収増進剤に対する該pH低下剤の重量比3:1-20 :1の固体の用量形態である、請求項1の医薬組成物。 23.該医薬組成物が該吸収増進剤に対する該pH低下剤の重量比5:1-1 0:1の固体の用量形態である、請求項1の医薬組成物。 24.該pH低下剤がクエン酸、酒石酸およびアミノ酸の酸性塩よりなる群から 選ばれる、請求項1の医薬組成物。 25.該pH低下剤が300mgより少なくない量で存在する、請求項1の医薬 組成物。 26.該pH低下剤が400mgより少なくない量で存在する、請求項25の医 薬組成物。 27.該ペプチド剤がバゾプレシンである、請求項1の医薬組成物。 28.該ペプチド剤がサケ・カルシトニンである、請求項1の医薬組成物。 29.該ペプチド剤がインスリンである、請求項1の医薬組成物。 30.該保護運搬剤が粘性保護シロップである、請求項1の医薬組成物。 31.該組成物がサケ・カルシトニンの経口用であって、 (A)治療上効果的な量の該サケ・カルシトニン; (B)少なくとも1種の薬学的に許容されるpH低下剤; (C)該サケ・カルシトニンのバイオアベイラビリティを促進するのに効果的 な少なくとも1種の吸収増進剤; (D)腸溶コーティング; (うち、pH低下剤は、該組成物を 0.1M 炭酸水素ナトリウム水溶液10mlに 加えたときに、該溶液のpHを5.5以下に下げるのに十分となる量で、該医薬組 成物中に存在する) を含む、請求項1の医薬組成物。 32.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも200 :1である、請求項31の医薬組成物。 33.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも800 :1である、請求項31の医薬組成物。 34.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも200 0:1である、請求項31の医薬組成物。 35.少なくとも一つのpH低下剤が 4.2 より大きくないpKaを有し、室温 で100mlに少なくとも30g溶ける水溶性を有する、請求項31の医薬組成 物。 36.水溶解性障壁が該pH低下剤を該腸溶コーティングから分離する、請求項 31の医薬組成物。 37.該サケ・カルシトニン、該pH低下剤および吸収増進剤が均一に分散して いる、請求項31の医薬組成物。 38.該腸溶コーティングが該腸溶コーティングを除く該医薬組成物の残余の重 量に対して30%以下の重量で存在する、請求項28の医薬組成物。 39.該組成物がサケ・カルシトニンの経口用であって、 (A)治療上効果的な量の該サケ・カルシトニン; (B)4.2 より大きくないpKaを有し、室温で100mlに少なくとも30 g溶ける水溶性を有する、少なくとも1種の薬学的に許容されるpH低下剤; (C)該サケ・カルシトニンのバイオアベイラビリティを促進するのに効果的 な少なくとも1種の吸収増進剤; (D)該医薬組成物の残余の重量に対して10%−20%の重量で存在する腸 溶コーティング; (E)該pH低下剤を該腸溶コーティングから分離する水溶性腸壁; (うち、pH低下剤は、該組成物を 0.1M 炭酸水素ナトリウム水溶液10mlに 加えたときに、該溶液のpHを5.5以下にするのに十分となる量で、該医薬組成 物中に存在する) を含む、請求項1の医薬組成物。 40.経口投与された治療的ペプチド活性剤のバイオアベイラビリティを高める ための方法であって、該ペプチド活性剤が少なくとも1種のpH低下剤および少 なくとも1種の吸収増進剤と共に、胃プロテアーゼと該ペプチド剤との接触を実 質的に防止する酸抵抗保護運搬剤の保護の下に該患者の口および胃を経て、次い で該ペプチド活性剤、pH低下剤および吸収増進剤が腸管中に選択的に放出され る方法(うち、該pH低下剤および他の化合物は、0.1M 炭酸水素ナトリウム水 溶液10mlに加えたときに、該溶液のpHを5.5以下に下げるのに十分となる量 で、該腸管中に放出される)。 41.該pH低下剤は、全成分を 0.1M 炭酸水素ナトリウム水溶液10mlに加え たときに、該溶液のpHを 3.5 以下にするのに十分となる量で、存在する、請 求項40の方法。 42.該保護運搬剤が、0.1N HCl 中で少なくとも2時間、他の成分の放出を防 止し、該保護運搬剤および他の成分を1分間100回転する分解浴でpHを6.3 まで増加した後、30分以内に全成分を完全に放出し得るのに十分である、請求 項40の方法。 43.該吸収増進剤がカチオン界面活性剤およびコレステロール誘導体であるア ニオン界面活性剤よりなる群から選ばれる、請求項40の方法。 44.該pH低下剤が 4.2 より大きくないpKaを有し、室温で100mlに 少なくとも30g溶ける水溶性を有する、請求項40の方法。 45.該吸収増進剤に対する該pH低下剤の重量比が 3:1-20:1である、 請求項40の方法。 46.該pH低下剤が300mgより少なくない量で存在する、請求項40の方 法。 47.該ペプチド剤がサケ・カルシトニンである、請求項40の方法。 48.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも800 :1である、請求項47の方法。 49.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも200 :1である、請求項47の方法。 50.該pH低下剤の該サケ・カルシトニンに対する重量比が少なくとも200 0:1である、請求項47の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/616,250 | 1996-03-15 | ||
US08/616,250 US5912014A (en) | 1996-03-15 | 1996-03-15 | Oral salmon calcitonin pharmaceutical products |
PCT/US1997/004024 WO1997033531A1 (en) | 1996-03-15 | 1997-03-14 | Oral peptide pharmaceutical products |
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JPH11508606A true JPH11508606A (ja) | 1999-07-27 |
JP3549542B2 JP3549542B2 (ja) | 2004-08-04 |
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JP53285997A Expired - Lifetime JP3549542B2 (ja) | 1996-03-15 | 1997-03-14 | 経口用ペプチド薬剤 |
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US (2) | US5912014A (ja) |
EP (1) | EP0929270B1 (ja) |
JP (1) | JP3549542B2 (ja) |
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CN1072964C (zh) * | 1994-04-22 | 2001-10-17 | 山之内制药株式会社 | 结肠特异性释药系统 |
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1996
- 1996-03-15 US US08/616,250 patent/US5912014A/en not_active Expired - Lifetime
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1997
- 1997-03-14 RU RU98118692/14A patent/RU2198677C2/ru not_active IP Right Cessation
- 1997-03-14 US US09/125,500 patent/US6086918A/en not_active Expired - Lifetime
- 1997-03-14 BR BR9708078A patent/BR9708078A/pt not_active Application Discontinuation
- 1997-03-14 AT AT97915071T patent/ATE284657T1/de active
- 1997-03-14 EP EP97915071A patent/EP0929270B1/en not_active Expired - Lifetime
- 1997-03-14 WO PCT/US1997/004024 patent/WO1997033531A1/en not_active Application Discontinuation
- 1997-03-14 PT PT97915071T patent/PT929270E/pt unknown
- 1997-03-14 NZ NZ331576A patent/NZ331576A/xx not_active IP Right Cessation
- 1997-03-14 CN CNB971930295A patent/CN1197616C/zh not_active Expired - Lifetime
- 1997-03-14 AU AU22111/97A patent/AU2211197A/en not_active Abandoned
- 1997-03-14 ES ES97915071T patent/ES2234011T3/es not_active Expired - Lifetime
- 1997-03-14 KR KR10-1998-0707287A patent/KR100498646B1/ko active IP Right Grant
- 1997-03-14 HU HU9902751A patent/HU226692B1/hu not_active IP Right Cessation
- 1997-03-14 CA CA002249744A patent/CA2249744C/en not_active Expired - Lifetime
- 1997-03-14 JP JP53285997A patent/JP3549542B2/ja not_active Expired - Lifetime
- 1997-03-14 DE DE69731957T patent/DE69731957T2/de not_active Expired - Lifetime
- 1997-03-14 CZ CZ983371A patent/CZ337198A3/cs unknown
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Cited By (9)
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JP2004525123A (ja) * | 2001-03-08 | 2004-08-19 | ユニジーン・ラボラトリーズ・インコーポレーテッド | 経口ペプチド医薬投与形および製造方法 |
JP2010184945A (ja) * | 2001-03-08 | 2010-08-26 | Unigene Lab Inc | 経口ペプチド医薬投与形および製造方法 |
JP2006517542A (ja) * | 2003-01-21 | 2006-07-27 | ユニジーン・ラボラトリーズ・インコーポレーテッド | 改善された経口ペプチド送達 |
US8314058B2 (en) | 2003-04-15 | 2012-11-20 | Axcess Limited | Uptake of macromolecules |
JP2012520262A (ja) * | 2009-03-12 | 2012-09-06 | ノルディック・ビオサイエンス・エー/エス | 糖尿病およびメタボリックシンドロームの治療 |
JP2013233094A (ja) * | 2012-05-07 | 2013-11-21 | Ueno Fine Chem Ind Ltd | 食品保存剤及び食品保存方法 |
JP2014114247A (ja) * | 2012-12-11 | 2014-06-26 | Capsugel Belgium Nv | 水中油型の乳剤およびその製造方法 |
JP2018501292A (ja) * | 2015-01-12 | 2018-01-18 | エンテリス・バイオファーマ・インコーポレイテッドEnteris Biopharma,Inc. | 固形経口剤形 |
JP2018043990A (ja) * | 2017-10-11 | 2018-03-22 | カプスゲル・ベルギウム・ナムローゼ・フェンノートシャップCapsugel Belgium NV | 水中油型の乳剤およびその製造方法 |
Also Published As
Publication number | Publication date |
---|---|
NZ331576A (en) | 2000-05-26 |
CZ337198A3 (cs) | 1999-04-14 |
US6086918A (en) | 2000-07-11 |
KR19990087798A (ko) | 1999-12-27 |
CA2249744A1 (en) | 1997-09-18 |
WO1997033531A1 (en) | 1997-09-18 |
NO322443B1 (no) | 2006-10-09 |
BR9708078A (pt) | 1999-07-27 |
CN1197616C (zh) | 2005-04-20 |
AU2211197A (en) | 1997-10-01 |
HUP9902751A2 (hu) | 2000-01-28 |
EP0929270B1 (en) | 2004-12-15 |
HU226692B1 (en) | 2009-06-29 |
PT929270E (pt) | 2005-04-29 |
DE69731957T2 (de) | 2005-12-15 |
CN1213282A (zh) | 1999-04-07 |
HUP9902751A3 (en) | 2001-04-28 |
ES2234011T3 (es) | 2005-06-16 |
KR100498646B1 (ko) | 2005-12-16 |
ATE284657T1 (de) | 2005-01-15 |
EP0929270A4 (en) | 2001-05-16 |
US5912014A (en) | 1999-06-15 |
EP0929270A1 (en) | 1999-07-21 |
CA2249744C (en) | 2002-04-09 |
RU2198677C2 (ru) | 2003-02-20 |
NO984243D0 (no) | 1998-09-14 |
DE69731957D1 (de) | 2005-01-20 |
NO984243L (no) | 1998-11-02 |
JP3549542B2 (ja) | 2004-08-04 |
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