RU2008124111A - PHARMACEUTICAL COMPOSITION FOR INCREASED EPITELIAL PERMEABILITY OF A GLUCOSURE-CONTROLLING PEPTIDE - Google Patents
PHARMACEUTICAL COMPOSITION FOR INCREASED EPITELIAL PERMEABILITY OF A GLUCOSURE-CONTROLLING PEPTIDE Download PDFInfo
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- RU2008124111A RU2008124111A RU2008124111/15A RU2008124111A RU2008124111A RU 2008124111 A RU2008124111 A RU 2008124111A RU 2008124111/15 A RU2008124111/15 A RU 2008124111/15A RU 2008124111 A RU2008124111 A RU 2008124111A RU 2008124111 A RU2008124111 A RU 2008124111A
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- Prior art keywords
- composition according
- cyclodextrin
- concentration
- chelator
- methyl
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- 230000035699 permeability Effects 0.000 title claims abstract 9
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 4
- 108090000765 processed proteins & peptides Proteins 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract 24
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract 10
- 239000002738 chelating agent Substances 0.000 claims abstract 10
- YZOUYRAONFXZSI-SBHWVFSVSA-N (1S,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-37,39,40,41,42,43,44,45,46,47,48,49-dodecamethoxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38-diol Chemical compound O([C@@H]([C@H]([C@@H]1OC)OC)O[C@H]2[C@@H](O)[C@@H]([C@@H](O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3O)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O3)O[C@@H]2CO)OC)[C@H](CO)[C@H]1O[C@@H]1[C@@H](OC)[C@H](OC)[C@H]3[C@@H](CO)O1 YZOUYRAONFXZSI-SBHWVFSVSA-N 0.000 claims abstract 8
- 239000002904 solvent Substances 0.000 claims abstract 8
- 108010011459 Exenatide Proteins 0.000 claims abstract 6
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims abstract 6
- 230000002708 enhancing effect Effects 0.000 claims abstract 6
- 229960001519 exenatide Drugs 0.000 claims abstract 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000001116 FEMA 4028 Substances 0.000 claims abstract 2
- 108010010803 Gelatin Proteins 0.000 claims abstract 2
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 claims abstract 2
- 230000001270 agonistic effect Effects 0.000 claims abstract 2
- 229960004853 betadex Drugs 0.000 claims abstract 2
- 125000002091 cationic group Chemical group 0.000 claims abstract 2
- 239000003795 chemical substances by application Substances 0.000 claims abstract 2
- 229950007919 egtazic acid Drugs 0.000 claims abstract 2
- 239000003623 enhancer Substances 0.000 claims abstract 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000008273 gelatin Substances 0.000 claims abstract 2
- 229920000159 gelatin Polymers 0.000 claims abstract 2
- 235000019322 gelatine Nutrition 0.000 claims abstract 2
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000338 in vitro Methods 0.000 claims abstract 2
- 229920000609 methyl cellulose Polymers 0.000 claims abstract 2
- 239000001923 methylcellulose Substances 0.000 claims abstract 2
- 235000010981 methylcellulose Nutrition 0.000 claims abstract 2
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 claims abstract 2
- 230000035515 penetration Effects 0.000 claims abstract 2
- 239000008389 polyethoxylated castor oil Substances 0.000 claims abstract 2
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 claims abstract 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims abstract 2
- 239000004475 Arginine Substances 0.000 claims 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims 1
- 206010061428 decreased appetite Diseases 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- -1 dimethyl β-cyclodextrin Chemical compound 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000037406 food intake Effects 0.000 claims 1
- 235000012631 food intake Nutrition 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 230000003880 negative regulation of appetite Effects 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 230000029537 positive regulation of insulin secretion Effects 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 230000036186 satiety Effects 0.000 claims 1
- 235000019627 satiety Nutrition 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
- 230000004580 weight loss Effects 0.000 claims 1
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- Medicinal Preparation (AREA)
Abstract
1. Водная фармацевтическая композиция для интраназальной доставки, содержащая терапевтически эффективное количество эксендина-4 или агонистического аналога эксендина-4, солюбилизирующий агент, усиливающий проницаемость, хелатор катионов, усиливающий проницаемость, буфер и возможно агент-усилитель вязкости, усиливающий проницаемость, где ! а) солюбилизирующий агент выбран из по меньшей мере одного из группы, состоящей из гидроксипропил-β-циклодекстрина, сульфобутилового эфира β-циклодекстрина, диметил-β-циклодекстрина, метил-β-циклодекстрина и кремофора EL, и ! б) усилитель вязкости выбран из по меньшей мере одного из группы, состоящей из желатина, метилцеллюлозы и гидроксипропилметилцеллюлозы, и где ! в) указанная композиция обеспечивает по меньшей мере 5%-ное проникание эксендина-4 в анализе проницаемости ткани in vitro, имеет вязкость вплоть до 150 сП (мПа·с), имеет рН от 2 до 8 и является стабильной по меньшей мере в течение двух недель при 5°С. ! 2. Композиция по п.1, где солюбилизирующий агент представляет собой метил-β-циклодекстрин. ! 3. Композиция по п.2, где метил-β-циклодекстрин присутствует в концентрации вплоть до 90 мг/мл. ! 4. Композиция по п.3, где метил-β-циклодекстрин присутствует в концентрации 80 мг/мл. ! 5. Композиция по п.1, где хелатор выбран из по меньшей мере одного из группы, состоящей из этилендиаминтетрауксусной кислоты и этиленгликольтетрауксусной кислоты. ! 6. Композиция по п.5, где хелатор присутствует в концентрации вплоть до 10 мг/мл. ! 7. Композиция по п.6, где хелатор присутствует в концентрации 5 мг/мл. ! 8. Композиция по п.1, где концентрация солюбилизирующего агента составляет 80 мг/мл, а концентрация хелатора1. An aqueous pharmaceutical composition for intranasal delivery, containing a therapeutically effective amount of exendin-4 or an agonistic analog of exendin-4, a permeability enhancing solubilizing agent, a permeability enhancing cationic chelator, a buffer, and possibly a permeability enhancing viscosity agent, where! a) the solubilizing agent is selected from at least one of the group consisting of hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, dimethyl-β-cyclodextrin, methyl-β-cyclodextrin and cremophor EL, and! b) the viscosity enhancer is selected from at least one of the group consisting of gelatin, methyl cellulose and hydroxypropyl methyl cellulose, and where! c) the specified composition provides at least 5% penetration of exendin-4 in the analysis of tissue permeability in vitro, has a viscosity of up to 150 cP (MPa · s), has a pH of 2 to 8 and is stable for at least two weeks at 5 ° C. ! 2. The composition according to claim 1, where the solubilizing agent is methyl β-cyclodextrin. ! 3. The composition according to claim 2, where methyl β-cyclodextrin is present in a concentration of up to 90 mg / ml. ! 4. The composition according to claim 3, where methyl β-cyclodextrin is present at a concentration of 80 mg / ml. ! 5. The composition according to claim 1, where the chelator is selected from at least one of the group consisting of ethylenediaminetetraacetic acid and ethylene glycoltetraacetic acid. ! 6. The composition according to claim 5, where the chelator is present in a concentration up to 10 mg / ml. ! 7. The composition according to claim 6, where the chelator is present at a concentration of 5 mg / ml. ! 8. The composition according to claim 1, where the concentration of the solubilizing agent is 80 mg / ml, and the concentration of the chelator
Claims (17)
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/293,676 US20060074025A1 (en) | 2003-12-26 | 2005-12-02 | Therapeutic formulations for transmucosal administration that increase glucagon-like peptide-1 bioavailability |
| US11/293,676 | 2005-12-02 | ||
| US77646406P | 2006-02-24 | 2006-02-24 | |
| US60/776,464 | 2006-02-24 | ||
| USPCT/US2006/008928 | 2006-03-03 | ||
| US80440606P | 2006-06-09 | 2006-06-09 | |
| US60/804,406 | 2006-06-09 | ||
| US60/804,543 | 2006-06-12 | ||
| US80519106P | 2006-06-19 | 2006-06-19 | |
| US60/805,191 | 2006-06-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2008124111A true RU2008124111A (en) | 2010-01-10 |
Family
ID=41643585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008124111/15A RU2008124111A (en) | 2005-12-02 | 2006-12-01 | PHARMACEUTICAL COMPOSITION FOR INCREASED EPITELIAL PERMEABILITY OF A GLUCOSURE-CONTROLLING PEPTIDE |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU2008124111A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2550798C2 (en) * | 2011-05-12 | 2015-05-10 | Василий Иосифович Зоря | Method of stimulating insulin secretion |
-
2006
- 2006-12-01 RU RU2008124111/15A patent/RU2008124111A/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2550798C2 (en) * | 2011-05-12 | 2015-05-10 | Василий Иосифович Зоря | Method of stimulating insulin secretion |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20110811 |