JP6363949B2 - 少なくとも中性塩および生物薬学的タンパク質を含む、水性製剤 - Google Patents
少なくとも中性塩および生物薬学的タンパク質を含む、水性製剤 Download PDFInfo
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- JP6363949B2 JP6363949B2 JP2014522080A JP2014522080A JP6363949B2 JP 6363949 B2 JP6363949 B2 JP 6363949B2 JP 2014522080 A JP2014522080 A JP 2014522080A JP 2014522080 A JP2014522080 A JP 2014522080A JP 6363949 B2 JP6363949 B2 JP 6363949B2
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- 239000004475 Arginine Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
・緩衝剤
・非イオン性界面活性剤
・等張化剤(tonifier) および/または
・保存料
よりなる群から選択される少なくとも1つの薬剤をさらに含む。
・リン酸緩衝剤(Na3PO4、NaH2PO4および/またはNa2HPO4)
・クエン酸塩、
・トリス、
・コハク酸塩、
・酢酸塩および/または
・ヒスチジン
よりなる群から選択される。
・ポロキサマー、好ましくはポロキサマー188またはポロキサマー184
・プルロニックF-68、および/または、
・ポリソルベート、好ましくはポリソルベート20またはポリソルベート80
よりなる群から選択される。
・マンニトール
・グリシン、および/または
・ソルビトール
よりなる群から選択される。
・フェノール
・メタクレゾール、
・メチルパラベン、
・プロピルパラベン、
・塩化ベンザルコニウム、
・塩化ベンゼトニウムおよび/または
・ベンジルアルコール
よりなる群から選択される。
・塩化ナトリウム(NaCl)
よりなる群から選択される。
・成長ホルモン欠損症
・在胎期間に比べて小さい(SGA)か、子宮内発育遅延(IUGR)
・特発性小人症
・AIDS消耗および悪液質
・ターナー症候群による低身長
・プラダーウィリ症候群による低身長
・短腸症候群による成長障害
・腎疾患を罹患する小児の成長異常
・リウマチ性関節炎
・骨粗鬆症
・X連鎖低リン酸血症性くる病
よりなる群から選択される、少なくとも1つの症状を治療するための、本発明による製剤の使用が提供される。
6つの製剤開発バッチ(等張化剤なし、グリシン、マンニトール、ソルビトール、およびNaCl)を比較した。水溶液中に15 mgのhGHを含むバッチ(10.0 mg/ml、注射用溶液1.5 mlカートリッジ)を5℃ ± 3℃(「所望の貯蔵条件」)で18ヶ月、25℃ ± 2℃/相対湿度60%(「加速貯蔵条件」)で3ヶ月、および40℃ ± 2℃(「過酷貯蔵条件」)で2週間、貯蔵した。種々の製剤を表4に示す。
6つの製剤開発バッチ(等張化剤なし、グリシン、マンニトール、ソルビトール、NaCl)を比較した。水溶液中に15 mgのhGHを含むバッチ(10.0 mg/ml、注射用溶液1.5 mlカートリッジ)を、5℃ ± 3℃(「所望の貯蔵条件」)で24ヶ月、25℃ ± 2℃/相対湿度60%(「加速貯蔵条件」)で3ヶ月、および40℃ ± 2℃(「過酷貯蔵条件」)で2週間、貯蔵した。種々の製剤を表5に示す。
8つの製剤開発バッチ(His/マンニトール、His/リン酸塩/マンニトール、アルギニン/リン酸塩/マンニトール、リン酸塩/マンニトール/0.41 mg/ml NaCl、リン酸塩/マンニトール/3.5 mg/ml NaCl、リン酸塩/7.07 mg/ml NaCl、リン酸塩/マンニトール/14 mg/ml NaClおよびリン酸塩/0.41 mg/ml NaCl)を比較した。水溶液中に15 mgのhGHを含むバッチ(10.0 mg/ml、注射用溶液1.5 mlカートリッジ)を、5℃ ± 3℃(「所望の貯蔵条件」)で24ヶ月および25℃ ± 2℃/相対湿度60%(「加速条件」)で3ヶ月貯蔵した。種々の製剤を表6に示す。
実験方法を以下の表およびリストに示す。
Claims (12)
- 少なくとも、塩化ナトリウムおよびヒト成長ホルモン(hGH)を含む、薬学的に許容される水性製剤であって、該塩化ナトリウムに対する該ヒト成長ホルモン(hGH)の濃度比が、≧1.4および≦2.86の範囲内である、製剤であって、さらに、非イオン性界面活性剤として、ポロキサマー、保存料として、フェノール、および、リン酸緩衝剤を含む、製剤。
- 請求項1に記載の製剤であって、該ヒト成長ホルモン(hGH)が、≧150および≦220の間のアミノ酸残基を有し、および/またはその分子量が≧15および≦26kダルトンの間である、製剤。
- 請求項1乃至2のいずれかに記載の製剤であって、前記の製剤が、等張化剤(tonifier)
よりなる群から選択される少なくとも1つの試薬をさらに含む、製剤。 - 請求項3に記載の製剤であって、前記リン酸緩衝剤が、Na3PO4、NaH2PO4および/またはNa2HPO4よりなる群から選択される、製剤。
- 請求項3〜4のいずれかに記載の製剤であって、該等張化剤(tonifier)が、
・マンニトール
・グリシン、および/または
・ソルビトール
よりなる群から選択される、製剤。 - 請求項3〜5のいずれかに記載の製剤であって、ヒト成長ホルモン(hGH)が、≧3と≦20mg ml―1との間の範囲の濃度で存在する、製剤。
- 請求項1乃至6のいずれかに記載の製剤であって、該塩化ナトリウムが、≧2と≦100mg ml―1との間の範囲の濃度で存在する、製剤。
- 請求項1乃至7のいずれかに記載の製剤であって、該製剤のpHが、≧5.8と≦6.2との間の範囲である、製剤。
- 請求項1乃至8のいずれかに記載の製剤であって、該製剤が、最適化された安定性を有する、製剤。
- ヒト成長ホルモン(hGH)を含む、薬学的に許容される水性製剤の安定性を高める方法であって、塩化ナトリウムに対するヒト成長ホルモン(hGH)のを最終濃度比が、≧1.4および≦2.86の範囲で提供され、該製剤は、さらに、非イオン性界面活性剤として、ポロキサマー、保存料として、フェノール、および、リン酸緩衝剤を含む、方法。
- 以下よりなる群から選択される、少なくとも1つの症状を治療するための、請求項1〜9のいずれかに記載の製剤。
・成長ホルモン欠損症
・在胎期間に比べて小さい(SGA)か、子宮内発育遅延(IUGR)
・特発性小人症
・AIDS消耗および悪液質
・ターナー症候群による低身長
・プラダーウィリ症候群による低身長
・短腸症候群による成長障害
・腎疾患を罹患する小児の成長異常
・リウマチ性関節炎
・骨粗鬆症
・X連鎖低リン酸血症性くる病。 - 請求項1〜9のいずれかに記載の製剤を含む、一次包装。
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US201161511168P | 2011-07-25 | 2011-07-25 | |
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PCT/EP2012/064613 WO2013014196A1 (en) | 2011-07-25 | 2012-07-25 | Aqueous formulation comprising at least a neutral salt and a biopharmaceutical protein |
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EP (1) | EP2736490A1 (ja) |
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EP3811962A4 (en) | 2018-06-25 | 2022-03-16 | JCR Pharmaceuticals Co., Ltd. | PROTEIN AQUEOUS LIQUID FORMULATION |
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US5981485A (en) * | 1997-07-14 | 1999-11-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
US5763394A (en) * | 1988-04-15 | 1998-06-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
AU686567C (en) * | 1992-07-31 | 2002-08-08 | Genentech Inc. | Human growth hormone aqueous formulation |
AUPN801296A0 (en) * | 1996-02-12 | 1996-03-07 | Csl Limited | Stabilised growth hormone formulation and method of preparation thereof |
JP3723857B2 (ja) * | 1998-02-04 | 2005-12-07 | 日本ケミカルリサーチ株式会社 | ヒト成長ホルモン含有水性医薬組成物 |
MXPA02000404A (es) | 1999-07-12 | 2004-05-21 | Grandis Biotech Gmbh | Formulaciones de hormona de crecimiento. |
AU2003250915A1 (en) * | 2002-07-09 | 2004-01-23 | Sandoz Ag | LIQUID FORMULATIONS WITH HIGH CONCENTRATION OF HUMAN GROWTH HORMONE (hgh) COMPRISING 1,2-PROLPYLENE GLYCOL |
EP1603588A2 (en) * | 2003-03-18 | 2005-12-14 | Ares Trading S.A. | Stabilisation of growth hormones in solution |
CA2551510C (en) * | 2003-12-23 | 2013-07-30 | Pharmacia Corporation | Stable growth hormone liquid formulation |
AU2005237775B2 (en) * | 2004-04-07 | 2010-03-04 | Ares Trading S.A. | Liquid growth hormone formulation |
EP2120869A2 (en) * | 2006-12-18 | 2009-11-25 | Altus Pharmaceuticals Inc. | Human growth hormone formulations |
KR101614983B1 (ko) * | 2009-11-17 | 2016-04-22 | 입센 파마 에스.에이.에스 | Hgh 및 rhigf―1의 조합물을 위한 제제 |
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US20180256722A1 (en) | 2018-09-13 |
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BR112014001921A2 (pt) | 2019-04-02 |
BR112014001921B1 (pt) | 2022-05-10 |
WO2013014196A1 (en) | 2013-01-31 |
US11446381B2 (en) | 2022-09-20 |
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