JP5732691B2 - インスリン製剤 - Google Patents
インスリン製剤 Download PDFInfo
- Publication number
- JP5732691B2 JP5732691B2 JP2010161767A JP2010161767A JP5732691B2 JP 5732691 B2 JP5732691 B2 JP 5732691B2 JP 2010161767 A JP2010161767 A JP 2010161767A JP 2010161767 A JP2010161767 A JP 2010161767A JP 5732691 B2 JP5732691 B2 JP 5732691B2
- Authority
- JP
- Japan
- Prior art keywords
- insulin
- preparation
- preparations
- concentration
- hours
- 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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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 160
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Classifications
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- 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
- A61K38/28—Insulins
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61K9/0012—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
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Description
[1]配列番号1の自己組織化ペプチドを含む、インスリン製剤。
[2]配列番号1の自己組織化ペプチドの濃度が、0.1〜0.25%(w/v)である、超即効型インスリン製剤。
[3]配列番号1の自己組織化ペプチドの濃度が、1.0〜2.0%(w/v)である、持効型インスリン製剤。
[4]インスリンが、野生型のインスリンである、上記[1]〜[3]のいずれか一に記載のインスリン製剤。
PMを超純水(ミリQ)に溶解して1%(w/v)及び3%(w/v)PMを調製した。なお、インスリンにはウシ膵臓由来のインスリン(29IU/mg)を用いた。
処方1. 0.2%(w/v)PMインスリン製剤
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 580μL
ミリQ 1740μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 1450μL
ミリQ 870μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 2320μL
ミリQ 0μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
3%(w/v)PM 1450μL
ミリQ 870μL
全量 2900μL
コントロールには1%(w/v)PMのみを投与した。ポジティブコントロールには現在、市販されている半合成ヒトインシュリンを含有する製剤(速効型水溶性製剤、ヒューマリン(登録商標)R)を使用した。
12時間〜16時間絶食させたWistar雄性ラット(9〜10週齢)にウレタン麻酔(1g/kg)を施し、麻酔下、各種インスリン製剤(処方1〜処方4)、コントロールおよびポジティブコントロール製剤を、腹部に皮下投与した。インスリンの投与量はすべて10IU/kg(最終濃度)とした。皮下投与前、皮下投与後30分、1、2、3、4、5、6、9、12、24時間後に頸静脈より全血100μLをヘパリン添加の遠心チューブに採血し、血漿を分離した。
PMの濃度が高くなるにつれて血糖降下度は大きくなった。0.5%(w/v)、0.8%(w/v)PM処方で、少なくとも6時間に渡る血漿中グルコース濃度の低下を認めた。また、血漿中グルコース濃度の最大低下度は、現在、臨床で使用されている速効型ヒューマリンR(Humulin R)と同程度であった。また、PM自体には血糖降下作用は認められなかった(図1)。
PM濃度が0.5%(w/v)の場合には、24時間に渡る血糖値の低下が認められた。PM濃度を1.5%(w/v)にすると、24時間を越える血糖値の低下が認められた(図2)。
PMを超純水(ミリQ)に溶解して1%(w/v)及び3%(w/v)PMを調製した。なお、インスリンにはウシ膵臓由来のインスリン(29IU/mg)を用いた。
処方1. 0.1%(w/v)PMインスリン製剤
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 290μL
ミリQ 2030μL
全量 2900μL
処方2. 0.25%(w/v)PMインスリン製剤
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 725μL
ミリQ 1595μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
1%(w/v)PM 1450μL
ミリQ 870μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
3%(w/v)PM 967μL
ミリQ 1353μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
3%(w/v)PM 1450μL
ミリQ 870μL
全量 2900μL
インスリン 5mg
0.01N HCL 580μL
3%(w/v)PM 1933μL
ミリQ 387μL
全量 2900μL
ポジティブコントロールには現在、市販されている半合成ヒトインシュリンを含有する製剤(速効型水溶性製剤、ヒューマリンR)を使用した。
12時間〜16時間絶食させたWistar雄性ラット(9〜10週齢)にウレタン麻酔(1g/kg)を施し、麻酔下、各種インスリン製剤(処方1〜処方6)、コントロールおよびポジティブコントロール製剤を、腹部に皮下投与した。インスリンの投与量はすべて10IU/kg(最終濃度)とした。皮下投与前、皮下投与後30分、1、2、3、4、5、6、9、12、24時間後に頸静脈より全血100μLをヘパリン添加の遠心チューブに採血し、血漿を分離した。
PMの濃度が高くなるにつれて血糖降下度は大きくなった。0.5%(w/v)、1.0%(w/v)、1.5%(w/v)、2.0%(w/v)PM処方で、少なくとも6時間に渡る血漿中グルコース濃度の低下を認めた。また、血漿中グルコース濃度の最大低下度は、現在、臨床で使用されている速効型ヒューマリンR(Humarin R)と同程度であった(図3)。
PM濃度が0.5%(w/v)、1.0%(w/v)、1.5%(w/v)、2.0%(w/v)の場合には、12時間を越える血糖値の低下が認められた(図4)。
PM濃度が1.0%(w/v)、1.5%(w/v)、2.0%(w/v)の場合には、24時間を越える血糖値の低下が認められた(図5)。
この図から、24時間でみたとき、2%PuraMatrixの効果は、ヒューマリンRの5倍であり、かつ長時間持続していることが分かる。
Claims (3)
- 2.0%(w/v)の配列番号1の自己組織化ペプチド及びインスリンを含む、糖尿病治療剤。
- インスリンが、野生型のインスリンである、請求項1に記載の糖尿病治療剤。
- 2.0%(w/v)の配列番号1の自己組織化ペプチド及びインスリンを含む持効型インスリン製剤、及び
0.1〜0.25%(w/v)の配列番号1の自己組織化ペプチド及びインスリンを含む超即効型インスリン製剤
を含む、併用糖尿病治療剤。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010161767A JP5732691B2 (ja) | 2010-01-14 | 2010-07-16 | インスリン製剤 |
EP11732894.8A EP2524698B1 (en) | 2010-01-14 | 2011-01-12 | Insulin preparation |
PCT/JP2011/050371 WO2011087024A1 (ja) | 2010-01-14 | 2011-01-12 | インスリン製剤 |
US13/522,157 US20120289462A1 (en) | 2010-01-14 | 2011-01-12 | Insulin preparation |
US14/176,902 US20140187482A1 (en) | 2010-01-14 | 2014-02-10 | Insulin preparation |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010005540 | 2010-01-14 | ||
JP2010005540 | 2010-01-14 | ||
JP2010161767A JP5732691B2 (ja) | 2010-01-14 | 2010-07-16 | インスリン製剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011162537A JP2011162537A (ja) | 2011-08-25 |
JP5732691B2 true JP5732691B2 (ja) | 2015-06-10 |
Family
ID=44304297
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010161767A Active JP5732691B2 (ja) | 2010-01-14 | 2010-07-16 | インスリン製剤 |
Country Status (4)
Country | Link |
---|---|
US (2) | US20120289462A1 (ja) |
EP (1) | EP2524698B1 (ja) |
JP (1) | JP5732691B2 (ja) |
WO (1) | WO2011087024A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2968135A4 (en) * | 2013-03-14 | 2016-10-26 | Massachusetts Inst Technology | INJECTABLE, MULTILAYER, SELF-COMPOSITE PEPTIDE RUBBER HYDROGELS FOR LONG-TERM AND DELAYED RELEASE OF HUMAN ANTIBODIES |
EP3164157A4 (en) * | 2014-07-01 | 2018-02-28 | Vicus Therapeutics, LLC | Hydrogels for treating and ameliorating cancers and potentiating the immune system and methods of making and using them |
US9987368B2 (en) | 2015-03-17 | 2018-06-05 | Santen Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising polypeptide |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5955343A (en) * | 1992-12-28 | 1999-09-21 | Massachusetts Institute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
WO2002062969A2 (en) * | 2001-02-06 | 2002-08-15 | Massachusetts Institute Of Technology | Cellular reprogramming in peptide hydrogel and uses thereof |
EP1833504A4 (en) * | 2005-01-04 | 2009-08-12 | Brigham & Womens Hospital | PERMANENT DELIVERY OF SELF-ARRANGING PEPTIDE NANOFIBER USING THE PDGF |
ES2534770T3 (es) * | 2007-12-05 | 2015-04-28 | 3-D Matrix, Ltd. | Material para la curación de heridas y la reconstrucción de la piel |
WO2009155334A1 (en) * | 2008-06-20 | 2009-12-23 | Escape Therapeutics, Inc. | Differentiation of mesenchymal stem cells into fibroblasts, compositions comprising mesenchymal stem cell-derived fibroblasts, and methods of using the same |
-
2010
- 2010-07-16 JP JP2010161767A patent/JP5732691B2/ja active Active
-
2011
- 2011-01-12 EP EP11732894.8A patent/EP2524698B1/en active Active
- 2011-01-12 US US13/522,157 patent/US20120289462A1/en not_active Abandoned
- 2011-01-12 WO PCT/JP2011/050371 patent/WO2011087024A1/ja active Application Filing
-
2014
- 2014-02-10 US US14/176,902 patent/US20140187482A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP2524698A1 (en) | 2012-11-21 |
EP2524698B1 (en) | 2018-11-21 |
JP2011162537A (ja) | 2011-08-25 |
EP2524698A4 (en) | 2013-09-04 |
US20120289462A1 (en) | 2012-11-15 |
US20140187482A1 (en) | 2014-07-03 |
WO2011087024A1 (ja) | 2011-07-21 |
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