RU2012136221A - Доставка активных веществ - Google Patents
Доставка активных веществ Download PDFInfo
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- RU2012136221A RU2012136221A RU2012136221/15A RU2012136221A RU2012136221A RU 2012136221 A RU2012136221 A RU 2012136221A RU 2012136221/15 A RU2012136221/15 A RU 2012136221/15A RU 2012136221 A RU2012136221 A RU 2012136221A RU 2012136221 A RU2012136221 A RU 2012136221A
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- active substance
- patient
- inhalation
- dry powder
- dosage form
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- 239000013543 active substance Substances 0.000 title claims abstract 17
- 238000000034 method Methods 0.000 claims abstract 29
- 239000000843 powder Substances 0.000 claims abstract 10
- 229940088597 hormone Drugs 0.000 claims abstract 9
- 239000005556 hormone Substances 0.000 claims abstract 9
- 239000002552 dosage form Substances 0.000 claims abstract 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract 6
- 230000002124 endocrine Effects 0.000 claims abstract 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 6
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 claims abstract 6
- 230000002685 pulmonary effect Effects 0.000 claims abstract 6
- 230000015556 catabolic process Effects 0.000 claims abstract 5
- 238000006731 degradation reaction Methods 0.000 claims abstract 5
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract 5
- 125000000349 (Z)-3-carboxyprop-2-enoyl group Chemical group O=C([*])/C([H])=C([H])\C(O[H])=O 0.000 claims abstract 3
- 208000008589 Obesity Diseases 0.000 claims abstract 3
- 239000003937 drug carrier Substances 0.000 claims abstract 3
- -1 glutaryl Chemical group 0.000 claims abstract 3
- 201000001421 hyperglycemia Diseases 0.000 claims abstract 3
- 235000020824 obesity Nutrition 0.000 claims abstract 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 3
- 108090000623 proteins and genes Proteins 0.000 claims abstract 3
- 102000004169 proteins and genes Human genes 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 claims abstract 3
- 230000007423 decrease Effects 0.000 claims abstract 2
- 210000005095 gastrointestinal system Anatomy 0.000 claims abstract 2
- 210000004185 liver Anatomy 0.000 claims abstract 2
- 230000002093 peripheral effect Effects 0.000 claims abstract 2
- 230000008320 venous blood flow Effects 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 229940112141 dry powder inhaler Drugs 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
Classifications
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K38/26—Glucagons
-
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- 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
-
- 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
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
1. Способ доставки активного вещества пациенту, нуждающемуся в этом, включающий:выбор активного вещества, подвергающегося деградации в организме указанного пациента, где эффективность указанного активного вещества уменьшается в результате указанной деградации;объединение указанного активного вещества с дикетопиперазином для получения фармацевтической композиции, подходящей для пульмональной ингаляции; ивведение указанной фармацевтической композиции указанному пациенту.2. Способ по п.1, в котором указанная деградация происходит в венозном кровотоке, в периферической ткани, в желудочно-кишечной системе или в печени.3. Способ по п.1, в котором указанный дикетопиперазин является 2,5-дикето-3,6-ди(4-X-аминобутил)пиперазином, где X выбран из группы, состоящей из сукцинила, глутарила, малеила и фумарила, или его фармацевтически приемлемой солью.4. Способ по п.1, в котором фармацевтическая композиция является сухой порошковой лекарственной формой для ингаляции.5. Способ по п.4, в котором указанная сухая порошковая лекарственная форма для ингаляции дополнительно включает фармацевтически приемлемый носитель или наполнитель.6. Способ по п.4, в котором сухую порошковую лекарственную форму для ингаляции вводят указанному пациенту путем пульмональной ингаляции с применением системы для ингаляции сухим порошком.7. Способ по п.1, в котором активное вещество является белком, пептидом или их аналогом.8. Способ по п.1, в котором активное вещество является эндокринным гормоном или его аналогом.9. Способ по п.8, в котором эндокринный гормон является гормоном, ассоциированным с диабетом, гипергликемией и/или ожирением.10. Способ по п.9, �
Claims (19)
1. Способ доставки активного вещества пациенту, нуждающемуся в этом, включающий:
выбор активного вещества, подвергающегося деградации в организме указанного пациента, где эффективность указанного активного вещества уменьшается в результате указанной деградации;
объединение указанного активного вещества с дикетопиперазином для получения фармацевтической композиции, подходящей для пульмональной ингаляции; и
введение указанной фармацевтической композиции указанному пациенту.
2. Способ по п.1, в котором указанная деградация происходит в венозном кровотоке, в периферической ткани, в желудочно-кишечной системе или в печени.
3. Способ по п.1, в котором указанный дикетопиперазин является 2,5-дикето-3,6-ди(4-X-аминобутил)пиперазином, где X выбран из группы, состоящей из сукцинила, глутарила, малеила и фумарила, или его фармацевтически приемлемой солью.
4. Способ по п.1, в котором фармацевтическая композиция является сухой порошковой лекарственной формой для ингаляции.
5. Способ по п.4, в котором указанная сухая порошковая лекарственная форма для ингаляции дополнительно включает фармацевтически приемлемый носитель или наполнитель.
6. Способ по п.4, в котором сухую порошковую лекарственную форму для ингаляции вводят указанному пациенту путем пульмональной ингаляции с применением системы для ингаляции сухим порошком.
7. Способ по п.1, в котором активное вещество является белком, пептидом или их аналогом.
8. Способ по п.1, в котором активное вещество является эндокринным гормоном или его аналогом.
9. Способ по п.8, в котором эндокринный гормон является гормоном, ассоциированным с диабетом, гипергликемией и/или ожирением.
10. Способ по п.9, в котором диабет является сахарным диабетом II типа.
11. Способ лечения заболевания, включающий:
выбор пациента, подвергаемого лечению, или пациента с патологическим состоянием, поддающимся лечению лабильным активным веществом;
предоставление композиции, включающей лабильное активное вещество в комбинации с дикетопиперазином; и
введение композиции пациенту посредством пульмональной ингаляции, с проведением, таким образом, лечения заболевания или патологического состояния.
12. Способ по п.11, в котором указанный дикетопиперазин является 2,5-дикето-3,6-ди(4-X-аминобутил)пиперазином, где X выбран из группы, состоящей из сукцинила, глутарила, малеила и фумарила, или его фармацевтически приемлемой солью.
13. Способ по п.11, в котором указанная композиция является сухой порошковой лекарственной формой для ингаляции.
14. Способ по п.13, в котором указанная сухая порошковая лекарственная форма для ингаляции дополнительно включает фармацевтически приемлемый носитель или наполнитель.
15. Способ по п.11, в котором активное вещество является пептидом или белком, или их аналогом.
16. Способ по п.11, в котором активное вещество является эндокринным гормоном или его аналогом.
17. Способ по п.16, в котором эндокринный гормон является гормоном, ассоциированным с диабетом, гипергликемией и/или ожирением.
18. Способ по п.17, в котором диабет является сахарным диабетом II типа.
19. Способ по п.11, в котором стадия введения указанной композиции указанному пациенту включает пульмональное введение указанной композиции с применением ингалятора сухого порошка, включающего картридж.
Applications Claiming Priority (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98236807P | 2007-10-24 | 2007-10-24 | |
| US60/982,368 | 2007-10-24 | ||
| US98562007P | 2007-11-05 | 2007-11-05 | |
| US60/985,620 | 2007-11-05 | ||
| US2227408P | 2008-01-18 | 2008-01-18 | |
| US61/022,274 | 2008-01-18 | ||
| US3374008P | 2008-03-04 | 2008-03-04 | |
| US61/033,740 | 2008-03-04 | ||
| US5212708P | 2008-05-09 | 2008-05-09 | |
| US61/052,127 | 2008-05-09 | ||
| US9482308P | 2008-09-05 | 2008-09-05 | |
| US61/094,823 | 2008-09-05 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010120672/15A Division RU2467741C2 (ru) | 2007-10-24 | 2008-10-24 | Доставка активных веществ |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2012136221A true RU2012136221A (ru) | 2014-02-27 |
Family
ID=40545981
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010120672/15A RU2467741C2 (ru) | 2007-10-24 | 2008-10-24 | Доставка активных веществ |
| RU2012136221/15A RU2012136221A (ru) | 2007-10-24 | 2012-08-23 | Доставка активных веществ |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010120672/15A RU2467741C2 (ru) | 2007-10-24 | 2008-10-24 | Доставка активных веществ |
Country Status (11)
| Country | Link |
|---|---|
| US (6) | US8372804B2 (ru) |
| EP (1) | EP2214647A2 (ru) |
| JP (2) | JP5813323B2 (ru) |
| KR (2) | KR20100090692A (ru) |
| CN (1) | CN101969928B (ru) |
| AU (1) | AU2008316636B2 (ru) |
| BR (1) | BRPI0818874A2 (ru) |
| CA (1) | CA2703234C (ru) |
| MX (1) | MX2010004508A (ru) |
| RU (2) | RU2467741C2 (ru) |
| WO (1) | WO2009055742A2 (ru) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
| EP1808438B1 (en) | 1999-06-29 | 2014-10-01 | MannKind Corporation | Purification and stabilization of peptide and proteins in pharmaceutical agents |
| ES2425392T3 (es) | 2002-03-20 | 2013-10-15 | Mannkind Corporation | Cartucho para un aparato de inhalación |
| US8921311B2 (en) | 2003-08-01 | 2014-12-30 | Mannkind Corporation | Method for treating hyperglycemia |
| DK1786784T3 (da) | 2004-08-20 | 2011-02-14 | Mannkind Corp | Katalyse af diketopiperazinsyntese |
| BR122019022692B1 (pt) | 2004-08-23 | 2023-01-10 | Mannkind Corporation | Composição terapêutica em pó seco contendo dicetopiperazina, pelo menos um tipo de cátion e um agente biologicamente ativo |
| WO2007033372A2 (en) | 2005-09-14 | 2007-03-22 | Mannkind Corporation | Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for active agents |
| DK1986679T3 (da) | 2006-02-22 | 2017-11-20 | Mannkind Corp | Fremgangsmåde til forbedring af mikropartiklers farmaceutiske egenskaber omfattende diketopiperazin og et aktivt indholdsstof |
| US8785396B2 (en) | 2007-10-24 | 2014-07-22 | Mannkind Corporation | Method and composition for treating migraines |
| KR20100090692A (ko) * | 2007-10-24 | 2010-08-16 | 맨카인드 코포레이션 | 활성제의 전달 |
| HUE025485T2 (en) * | 2007-10-24 | 2016-02-29 | Mannkind Corp | Respiratory dry powder formulation containing GLP-1 for use in the treatment of hyperglycemia and diabetes by pulmonary administration |
| CA3153292A1 (en) | 2008-06-13 | 2009-12-17 | Mannkind Corporation | A dry powder inhaler and system for drug delivery |
| US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
| CN102065942B (zh) | 2008-06-20 | 2013-12-11 | 曼金德公司 | 用于对吸入工作进行实时描绘的交互式设备和方法 |
| TWI532497B (zh) | 2008-08-11 | 2016-05-11 | 曼凱公司 | 超快起作用胰島素之用途 |
| US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
| US20100169260A1 (en) * | 2008-12-30 | 2010-07-01 | Searete Llc | Methods and systems for presenting an inhalation experience |
| US20100163029A1 (en) | 2008-12-30 | 2010-07-01 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for administering an inhalable compound |
| DK2379100T3 (en) | 2009-01-08 | 2014-12-01 | Mannkind Corp | Treatment of hyperglycemia with GLP-1 |
| PL2405963T3 (pl) | 2009-03-11 | 2014-04-30 | Mannkind Corp | Urządzenie, układ i sposób pomiaru oporu inhalatora |
| BRPI1010722B1 (pt) * | 2009-06-12 | 2019-12-10 | Mannkind Corp | micropartículas de dicetopiperazina com teores de isômero definidos, pó seco, uso de uma formulação de pó seco compreendendo micropartículas de dicetopiperazina, método de preparar micropartículas e método para sintetizar uma dicetopiperazina |
| KR20180036807A (ko) * | 2009-06-12 | 2018-04-09 | 맨카인드 코포레이션 | 한정된 비표면적을 갖는 디케토피페라진 마이크로입자 |
| JP5981343B2 (ja) * | 2009-11-02 | 2016-08-31 | マンカインド コーポレ−ション | 析出プロセスにおいて医薬粒子を生成するための反応器 |
| RU2638794C2 (ru) * | 2009-11-02 | 2017-12-15 | Мэннкайнд Корпорэйшн | Способ криогрануляции фармацевтической композиции |
| AU2015201885B2 (en) * | 2009-11-02 | 2017-04-20 | Mannkind Corporation | Apparatus and method for cryogranulating a pharmaceutical composition |
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| CA2703234C (en) | 2021-10-26 |
| CN101969928B (zh) | 2014-05-07 |
| AU2008316636B2 (en) | 2014-02-06 |
| MX2010004508A (es) | 2010-07-02 |
| US20090111749A1 (en) | 2009-04-30 |
| CA2703234A1 (en) | 2009-04-30 |
| US20240197627A1 (en) | 2024-06-20 |
| EP2214647A2 (en) | 2010-08-11 |
| JP5813323B2 (ja) | 2015-11-17 |
| US20200146981A1 (en) | 2020-05-14 |
| CN101969928A (zh) | 2011-02-09 |
| WO2009055742A3 (en) | 2009-06-11 |
| KR20130123470A (ko) | 2013-11-12 |
| RU2467741C2 (ru) | 2012-11-27 |
| JP2011500851A (ja) | 2011-01-06 |
| JP2015227357A (ja) | 2015-12-17 |
| US8372804B2 (en) | 2013-02-12 |
| WO2009055742A2 (en) | 2009-04-30 |
| BRPI0818874A2 (pt) | 2015-05-05 |
| KR20100090692A (ko) | 2010-08-16 |
| RU2010120672A (ru) | 2011-11-27 |
| US20130118491A1 (en) | 2013-05-16 |
| US20190167580A1 (en) | 2019-06-06 |
| US20220362147A1 (en) | 2022-11-17 |
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