RU2003117702A - Применение бисфосфонатов для лечения боли - Google Patents
Применение бисфосфонатов для лечения боли Download PDFInfo
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- RU2003117702A RU2003117702A RU2003117702/14A RU2003117702A RU2003117702A RU 2003117702 A RU2003117702 A RU 2003117702A RU 2003117702/14 A RU2003117702/14 A RU 2003117702/14A RU 2003117702 A RU2003117702 A RU 2003117702A RU 2003117702 A RU2003117702 A RU 2003117702A
- Authority
- RU
- Russia
- Prior art keywords
- bisphosphonate
- acid
- treatment
- diphosphonic acid
- pain
- Prior art date
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- 229940122361 Bisphosphonate Drugs 0.000 title claims abstract 14
- 150000004663 bisphosphonates Chemical class 0.000 title claims abstract 14
- 238000000034 method Methods 0.000 claims abstract 8
- 150000003839 salts Chemical class 0.000 claims abstract 5
- 230000003574 anti-allodynic effect Effects 0.000 claims abstract 4
- 230000003502 anti-nociceptive effect Effects 0.000 claims abstract 4
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims abstract 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract 2
- 208000001132 Osteoporosis Diseases 0.000 claims abstract 2
- 150000004677 hydrates Chemical class 0.000 claims abstract 2
- 229960004276 zoledronic acid Drugs 0.000 claims abstract 2
- -1 for example Chemical compound 0.000 claims 12
- 125000000217 alkyl group Chemical group 0.000 claims 7
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- PMXAPNNYCFBALB-UHFFFAOYSA-N (1-hydroxy-1-phosphono-3-pyrrolidin-1-ylpropyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCN1CCCC1 PMXAPNNYCFBALB-UHFFFAOYSA-N 0.000 claims 3
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims 3
- 206010006002 Bone pain Diseases 0.000 claims 3
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims 3
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims 3
- 229940126601 medicinal product Drugs 0.000 claims 3
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims 3
- NPLHDPAQRZJWHX-UHFFFAOYSA-N [5,5-bis(diethoxyphosphoryl)-1,4-dihydropyrazol-3-yl]-phenylmethanone Chemical compound N1C(P(=O)(OCC)OCC)(P(=O)(OCC)OCC)CC(C(=O)C=2C=CC=CC=2)=N1 NPLHDPAQRZJWHX-UHFFFAOYSA-N 0.000 claims 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229960002286 clodronic acid Drugs 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- VPTUPAVOBUEXMZ-UHFFFAOYSA-N (1-hydroxy-2-phosphonoethyl)phosphonic acid Chemical compound OP(=O)(O)C(O)CP(O)(O)=O VPTUPAVOBUEXMZ-UHFFFAOYSA-N 0.000 claims 1
- RDFHOSXBGDLRQF-UHFFFAOYSA-N (2-anilino-1-phosphono-2-sulfanylideneethyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)C(=S)NC1=CC=CC=C1 RDFHOSXBGDLRQF-UHFFFAOYSA-N 0.000 claims 1
- HLNJFEXZDGURGZ-UHFFFAOYSA-M 1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1 HLNJFEXZDGURGZ-UHFFFAOYSA-M 0.000 claims 1
- NEAHTABRXFKZGG-UHFFFAOYSA-N 2-pyridin-4-yl-3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=CC(C=2NC3=CN=CC=C3N=2)=C1 NEAHTABRXFKZGG-UHFFFAOYSA-N 0.000 claims 1
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- VADUXZPJGJBSLQ-UHFFFAOYSA-N [1-hydroxy-3-(1-methylpyridin-1-ium-3-yl)-1-phosphonopropyl]phosphonic acid;hydroxide Chemical compound [OH-].C[N+]1=CC=CC(CCC(O)(P(O)(O)=O)P(O)(O)=O)=C1 VADUXZPJGJBSLQ-UHFFFAOYSA-N 0.000 claims 1
- QWCNOXMFNSYEKF-UHFFFAOYSA-N [1-hydroxy-3-[methyl(2-phenylsulfanylethyl)amino]-1-phosphonopropyl]phosphonic acid Chemical compound OP(=O)(O)C(O)(P(O)(O)=O)CCN(C)CCSC1=CC=CC=C1 QWCNOXMFNSYEKF-UHFFFAOYSA-N 0.000 claims 1
- UGEPSJNLORCRBO-UHFFFAOYSA-N [3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O UGEPSJNLORCRBO-UHFFFAOYSA-N 0.000 claims 1
- 229940062527 alendronate Drugs 0.000 claims 1
- 229960004343 alendronic acid Drugs 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- JFGHPLSPUGOSLV-UHFFFAOYSA-L disodium;[3-(dimethylamino)-1-hydroxy-1-[hydroxy(oxido)phosphoryl]propyl]-hydroxyphosphinate Chemical compound [Na+].[Na+].CN(C)CCC(O)(P(O)(O)=O)P([O-])([O-])=O JFGHPLSPUGOSLV-UHFFFAOYSA-L 0.000 claims 1
- 229960004585 etidronic acid Drugs 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 230000012010 growth Effects 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 229940015872 ibandronate Drugs 0.000 claims 1
- 229960005236 ibandronic acid Drugs 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 230000009545 invasion Effects 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 229940046231 pamidronate Drugs 0.000 claims 1
- 229960003978 pamidronic acid Drugs 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 229940089617 risedronate Drugs 0.000 claims 1
- 229960000759 risedronic acid Drugs 0.000 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 229940019375 tiludronate Drugs 0.000 claims 1
- 229960005324 tiludronic acid Drugs 0.000 claims 1
- 230000005740 tumor formation Effects 0.000 claims 1
- 208000029725 Metabolic bone disease Diseases 0.000 abstract 1
- 206010049088 Osteopenia Diseases 0.000 abstract 1
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
Classifications
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (9)
1. Способ лечения боли у пациента, нуждающегося в таком лечении, который заключается в введении пациенту эффективного количества бисфосфоната.
2. Применение бисфосфоната для приготовления лекарственного средства, предназначенного для лечения боли.
3. Применение бисфосфоната для лечения у млекопитающего боли, связанной с заболеваниями или патологическими состояниями.
4. Способ антиноцицептивного или антиаллодинического лечения боли у пациента, нуждающегося в таком лечении, который заключается во введении пациенту эффективного количества бисфосфоната;
применение бисфосфоната для приготовления лекарственного средства, предназначенного для антиноцицептивного или антиаллодинического лечения боли; или
применение бисфосфоната в качестве антиноцицептивного или антиаллодинического агента.
5. Способ лечения боли костной ткани у пациента, нуждающегося в таком лечении, который заключается во введении пациенту эффективного количества бисфосфоната;
применение бисфосфоната для приготовления лекарственного средства, предназначенного для лечения боли костной ткани; или
применение бисфосфоната в качестве агента для лечения боли костной ткани.
6. Способ по п.1 или применение по п.2 или 3 для лечения боли, связанной с остеопорозом, ревматоидным артритом, остеоартритом и образованием опухоли, например, с ростом, инвазией или метастазами опухоли.
7. Способ по п.1 или применение по п.2 или 3, где бисфософнат выбирают из следующих соединений или их фармацевтически приемлемых солей или любых гидратов:
3-амино-1-гидроксипропан-1,1-дифосфоновая кислота (памидроновая кислота), например, памидронат (APD); 3-(N,N-диметиламино)-1-гидроксипропан-1,1-дифосфоновая кислота, например, диметил-APD; 4-амино-1-гидроксибутан-1,1-дифосфоновая кислота (алендроновая кислота), например, алендронат; 1-гидроксиэтиденбисфосфоновая кислота, например, этидронат; 1-гидрокси-3-(метилпентиламино)пропилиденбисфосфоновая кислота, ибандроновая кислота, например, ибандронат; 6-амино-1-гидроксигексан-1,1-дифосфоновая кислота, например, аминогексил-ВР; 3-(N-метил-N-н-пентиламино)-1 -гидроксипропан-1,1 -дифосфоновая кислота, например, метилпентил-APD (=ВМ 21.0955); 1-гидрокси-2-(имидазол-1-ил)этан-1,1-дифосфоновая кислота; 1-гидрокси-2-(3-пиридил)этан-1,1-дифосфоновая кислота (ризедроновая кислота), например, ризедронат, включая ее N-метилпиридиевые соли, например, йодид N-метилпиридиния, такой как NE-10244 или NE-10446; 1-(4-хлорфенилтио)метан-1,1-дифосфоновая кислота (тилудроновая кислота), например, тилудронат; 3-[N-(2-фенилтиоэтил)-N-метиламино]-1-гидроксипропан-1,1-дифосфоновая кислота; 1-гидрокси-3-(пирролидин-1-ил)пропан-1,1-дифосфоновая кислота, например, ЕВ 1053 (фирма Leo); 1-(N-фениламинотиокарбонил)метан-1,1-дифосфоновая кислота, например, FR 78844 (фирма Fujisawa); тетраэтиловый эфир 5-бензоил-3,4-дигидро-2Н-пиразол-3,3-дифосфоновой кислоты, например, U-81581 (фирма Upjohn); 1-гидрокси-2-(имидазо[1,2-а]пиридин-3-ил)этан-1,1-дифосфоновая кислота, например, YM 529; и 1,1-дихлорметан-1,1-дифосфоновая кислота (клодроновая кислота), например, клодронат.
8. Способ по п.1 или применение по п.2 или 3, где бисфосфонат представляет собой соединение формулы III
где
Het’’ обозначает имидазолил, 2Н-1,2,3-, 1H-1,2,4- или 4Н-1,2,4-триазолил, тетразолил, оксазолил, изоксазолил, оксадиазолил, тиазолил или тиадиазолил, незамещенные или С-моно- или дизамещенные (низш.)алкилом, (низш.)алкоксигруппой, фенилом, который в свою очередь может быть моно- или дизамещен (низш.)алкилом, (низш.)алкоксигруппой и/или галогеном, гидроксигруппой, ди(низш.)алкиламиногруппой, (низш.)алкилтиогруппой и/или галогеном, и N-замещенные на замещаемом атоме N (низш.)алкилом или фенил(низш.)алкилом, который в свою очередь может быть моно- или дизамещен в фенильном фрагменте (низш.)алкилом, (низш.)алкоксигруппой и/или галогеном, и
R2 обозначает водород, гидрокси, амино, (низш.)алкилтио или галоген,
где (низш.)радикалы имеют до 7 включительно атомов углерода,
или его фармакологически приемлемую соль.
9. Способ по п.1 или применение по п.2 или 3, где бисфосфонат представляет собой золедроновую кислоту или ее фармацевтически приемлемую соль или любой гидрат.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0029111.2 | 2000-11-29 | ||
| GBGB0029111.2A GB0029111D0 (en) | 2000-11-29 | 2000-11-29 | Organic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2003117702A true RU2003117702A (ru) | 2005-02-27 |
| RU2325913C2 RU2325913C2 (ru) | 2008-06-10 |
Family
ID=9904112
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003117702/14A RU2325913C2 (ru) | 2000-11-29 | 2001-11-27 | Применение золедроновой кислоты, ее солей, гидратов и способ антиноцицептивного или антиаллодинического лечения боли, способ лечения невропатической боли |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US20040063670A1 (ru) |
| EP (1) | EP1339411B1 (ru) |
| JP (1) | JP2004514696A (ru) |
| KR (2) | KR100866025B1 (ru) |
| CN (1) | CN1535152A (ru) |
| AT (1) | ATE366112T1 (ru) |
| AU (2) | AU1706102A (ru) |
| BR (1) | BR0115696A (ru) |
| CA (1) | CA2427161C (ru) |
| CY (1) | CY1106851T1 (ru) |
| CZ (1) | CZ301701B6 (ru) |
| DE (1) | DE60129242T2 (ru) |
| DK (1) | DK1339411T3 (ru) |
| ES (1) | ES2287191T3 (ru) |
| GB (1) | GB0029111D0 (ru) |
| HU (1) | HUP0302556A3 (ru) |
| IL (2) | IL155363A0 (ru) |
| MX (1) | MXPA03004815A (ru) |
| NO (1) | NO20032405L (ru) |
| NZ (1) | NZ525871A (ru) |
| PL (1) | PL204001B1 (ru) |
| PT (1) | PT1339411E (ru) |
| RU (1) | RU2325913C2 (ru) |
| SK (1) | SK287501B6 (ru) |
| TW (1) | TWI275393B (ru) |
| WO (1) | WO2002043738A2 (ru) |
| ZA (1) | ZA200303247B (ru) |
Families Citing this family (95)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7658938B2 (en) | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
| US8119159B2 (en) | 1999-02-22 | 2012-02-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| CN1233325C (zh) | 2001-02-06 | 2005-12-28 | 罗亚尔·亚历山德拉儿童医院 | 治疗骨坏死和处理有发展为骨坏死危险的患者用的药物 |
| US7875597B2 (en) * | 2002-07-24 | 2011-01-25 | New York University | Treatment of spinal mechanical pain |
| WO2005072746A1 (ja) * | 2004-01-30 | 2005-08-11 | Astellas Pharma Inc. | P2x受容体阻害剤 |
| AU2005240107A1 (en) * | 2004-05-06 | 2005-11-17 | Merck & Co., Inc. | Methods for treating arthritic conditions in dogs |
| KR20070043043A (ko) * | 2004-08-23 | 2007-04-24 | 테바 파마슈티컬 인더스트리즈 리미티드 | 고체 및 결정 이반드로네이트 나트륨 및 이들의 제조 방법 |
| US7473684B2 (en) * | 2005-09-16 | 2009-01-06 | Selamine Limited | Bisphosphonate formulation |
| BRPI0615770A2 (pt) | 2005-09-16 | 2011-05-24 | Selamine Ltd | formulação de bisfosfonato |
| BRPI0710503A2 (pt) | 2006-04-07 | 2011-08-16 | Merrion Res Iii Ltd | uso de uma composição farmacêutica, composição farmacêutica, e, forma de dosagem oral |
| GB0624090D0 (en) * | 2006-12-01 | 2007-01-10 | Selamine Ltd | Ramipril amine salts |
| GB0624087D0 (en) * | 2006-12-01 | 2007-01-10 | Selamine Ltd | Ramipril combination salt |
| GB0624084D0 (en) * | 2006-12-01 | 2007-01-10 | Selamine Ltd | Ramipril amino acid salts |
| US8974801B2 (en) | 2006-12-21 | 2015-03-10 | Amphastar Pharmaceuticals Inc. | Long term sustained release pharmaceutical composition containing aqueous suspension of bisphosphonate |
| ITPA20070034A1 (it) * | 2007-10-30 | 2009-04-30 | Tetrapharm S R L | Bifosfonati geminali, loro preparazione e loro impiego in campo oncologico. |
| MX2010005786A (es) | 2007-11-30 | 2010-06-09 | Novartis Ag | Bisfosfonatos de alquilo de 2 a 5 atomos de carbono-imidazol. |
| EA201001578A1 (ru) * | 2008-04-04 | 2011-06-30 | Новартис Аг | Фармацевтическая композиция с бисфосфонатом |
| US20090280169A1 (en) | 2008-05-07 | 2009-11-12 | Merrion Research Iii Limited | Compositions of peptides and processes of preparation thereof |
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