JP2012500196A5 - - Google Patents
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- JP2012500196A5 JP2012500196A5 JP2011523004A JP2011523004A JP2012500196A5 JP 2012500196 A5 JP2012500196 A5 JP 2012500196A5 JP 2011523004 A JP2011523004 A JP 2011523004A JP 2011523004 A JP2011523004 A JP 2011523004A JP 2012500196 A5 JP2012500196 A5 JP 2012500196A5
- Authority
- JP
- Japan
- Prior art keywords
- item
- pharmaceutical composition
- linaclotide
- composition according
- leucine
- 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.)
- Granted
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 222
- 108010024409 linaclotide Proteins 0.000 claims description 202
- 229960000812 linaclotide Drugs 0.000 claims description 202
- KXGCNMMJRFDFNR-WDRJZQOASA-N linaclotide Chemical compound C([C@H](NC(=O)[C@@H]1CSSC[C@H]2C(=O)N[C@H]3CSSC[C@H](N)C(=O)N[C@H](C(N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N2)=O)CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC3=O)C(=O)N[C@H](C(NCC(=O)N1)=O)[C@H](O)C)C(O)=O)C1=CC=C(O)C=C1 KXGCNMMJRFDFNR-WDRJZQOASA-N 0.000 claims description 192
- 238000000034 method Methods 0.000 claims description 113
- 239000002552 dosage form Substances 0.000 claims description 85
- 239000011575 calcium Substances 0.000 claims description 61
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 52
- 235000005772 leucine Nutrition 0.000 claims description 52
- 229960003136 leucine Drugs 0.000 claims description 52
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 46
- 150000001413 amino acids Chemical class 0.000 claims description 41
- 150000003141 primary amines Chemical class 0.000 claims description 41
- 229940024606 amino acid Drugs 0.000 claims description 40
- 235000001014 amino acid Nutrition 0.000 claims description 40
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 32
- 239000011701 zinc Substances 0.000 claims description 31
- 239000011777 magnesium Substances 0.000 claims description 30
- 239000000945 filler Substances 0.000 claims description 27
- 206010010774 Constipation Diseases 0.000 claims description 24
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 22
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 22
- 239000001110 calcium chloride Substances 0.000 claims description 22
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 22
- 235000011148 calcium chloride Nutrition 0.000 claims description 22
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 22
- 150000001768 cations Chemical class 0.000 claims description 21
- 239000011572 manganese Substances 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 20
- 235000002639 sodium chloride Nutrition 0.000 claims description 20
- 230000007062 hydrolysis Effects 0.000 claims description 18
- 238000006460 hydrolysis reaction Methods 0.000 claims description 18
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 18
- 230000003647 oxidation Effects 0.000 claims description 18
- 238000007254 oxidation reaction Methods 0.000 claims description 18
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 17
- 235000006109 methionine Nutrition 0.000 claims description 17
- 229930182817 methionine Natural products 0.000 claims description 17
- 229960004452 methionine Drugs 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 16
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 16
- 235000011147 magnesium chloride Nutrition 0.000 claims description 16
- 239000004246 zinc acetate Substances 0.000 claims description 16
- 235000013904 zinc acetate Nutrition 0.000 claims description 16
- 239000011230 binding agent Substances 0.000 claims description 14
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 13
- 239000002775 capsule Substances 0.000 claims description 13
- 235000014705 isoleucine Nutrition 0.000 claims description 13
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 13
- 229960000310 isoleucine Drugs 0.000 claims description 13
- 229910021380 Manganese Chloride Inorganic materials 0.000 claims description 11
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims description 11
- 239000001506 calcium phosphate Substances 0.000 claims description 11
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 11
- 235000011010 calcium phosphates Nutrition 0.000 claims description 11
- 239000011565 manganese chloride Substances 0.000 claims description 11
- 235000002867 manganese chloride Nutrition 0.000 claims description 11
- 229940099607 manganese chloride Drugs 0.000 claims description 11
- 239000001103 potassium chloride Substances 0.000 claims description 11
- 235000011164 potassium chloride Nutrition 0.000 claims description 11
- 239000011780 sodium chloride Substances 0.000 claims description 11
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 11
- 239000003963 antioxidant agent Substances 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 229920002678 cellulose Polymers 0.000 claims description 10
- 239000001913 cellulose Substances 0.000 claims description 10
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- 229920003086 cellulose ether Polymers 0.000 claims description 10
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 10
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 10
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 10
- 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 description 10
- 239000000243 solution Substances 0.000 claims description 10
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 9
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 9
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 9
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 9
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 9
- 235000004279 alanine Nutrition 0.000 claims description 9
- 229960003767 alanine Drugs 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 235000014304 histidine Nutrition 0.000 claims description 9
- 229960002885 histidine Drugs 0.000 claims description 9
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 9
- 235000008729 phenylalanine Nutrition 0.000 claims description 9
- 229960005190 phenylalanine Drugs 0.000 claims description 9
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 229960004799 tryptophan Drugs 0.000 claims description 9
- 229960004295 valine Drugs 0.000 claims description 9
- 239000004474 valine Substances 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 230000002269 spontaneous effect Effects 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- 239000011324 bead Substances 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 6
- 238000000576 coating method Methods 0.000 claims description 6
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 5
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 5
- 239000004473 Threonine Substances 0.000 claims description 5
- 206010000059 abdominal discomfort Diseases 0.000 claims description 5
- 235000009582 asparagine Nutrition 0.000 claims description 5
- 229960001230 asparagine Drugs 0.000 claims description 5
- 235000003704 aspartic acid Nutrition 0.000 claims description 5
- 229960005261 aspartic acid Drugs 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- 235000013922 glutamic acid Nutrition 0.000 claims description 5
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- 239000004220 glutamic acid Substances 0.000 claims description 5
- 235000004554 glutamine Nutrition 0.000 claims description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 5
- 229960002743 glutamine Drugs 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 235000008521 threonine Nutrition 0.000 claims description 5
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- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims description 4
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
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- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 4
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- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 5
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| JP5964589B2 (ja) | 2008-12-03 | 2016-08-03 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼｃアゴニストの製剤およびその使用方法 |
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| CN104053449B (zh) * | 2011-08-17 | 2016-12-07 | 硬木药品公司 | 胃肠疾患的治疗 |
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| CA2920856C (en) | 2013-08-09 | 2026-03-03 | Ardelyx, Inc. | Ph modulating compounds for inhibiting gastrointestinal phosphate uptake |
| UA119335C2 (uk) | 2013-12-11 | 2019-06-10 | Айронвуд Фармасьютикалз, Інк. | Композиції лінаклотиду з затриманим вивільненням |
| US10272131B2 (en) | 2014-08-11 | 2019-04-30 | Sun Pharmaceutical Industries Ltd. | Linaclotide stable composition |
| DK3006045T3 (en) * | 2014-10-07 | 2017-07-17 | Cyprumed Gmbh | Pharmaceutical formulations for oral administration of peptide or protein drugs |
| CN104569245A (zh) * | 2014-12-08 | 2015-04-29 | 江苏泰洁检测技术有限公司 | 一种工作场所脂肪族胺类中环己胺浓度测定方法 |
| WO2016125064A1 (en) * | 2015-02-02 | 2016-08-11 | Aurobindo Pharma Ltd | Stable compositions comprising linaclotide |
| JP2018516937A (ja) * | 2015-06-05 | 2018-06-28 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | リナクロチドの改変または標的放出製剤 |
| EP3359181A1 (en) | 2015-10-07 | 2018-08-15 | Cyprumed GmbH | Pharmaceutical formulations for the oral delivery of peptide drugs |
| CN110475564A (zh) | 2016-12-21 | 2019-11-19 | 硬木药品公司 | 用利那洛肽的修饰的或延迟释放制剂治疗肠易激综合征的方法 |
| CN107669700A (zh) * | 2017-09-14 | 2018-02-09 | 湖南晓林生物科技发展有限公司 | 一种治疗溃疡性结肠炎的药物及其制备方法 |
| WO2020012243A2 (en) | 2018-07-09 | 2020-01-16 | Abbott Laboratories Gmbh | Pharmaceutical composition containing a peptide |
| JP2022533251A (ja) | 2019-05-21 | 2022-07-21 | アルデリックス， インコーポレイテッド | 患者において血清リン酸塩を低下させるための組み合わせ |
| CN112121021B (zh) * | 2019-06-24 | 2022-03-25 | 深圳翰宇药业股份有限公司 | 一种含利那洛肽的药物组合物及其制备方法 |
| JP2021104941A (ja) * | 2019-12-26 | 2021-07-26 | ニプロ株式会社 | 薬物高含有量錠剤及びその製造方法 |
| JP7599014B2 (ja) * | 2020-06-30 | 2024-12-12 | オクヴィルク，ゼレン | グアニル酸シクラーゼｃ（ｇｕｃｙ２ｃ）アゴニストおよび短鎖脂肪酸またはそのプロドラッグの組み合わせを含む医薬組成物 |
| CN115105582A (zh) * | 2021-03-17 | 2022-09-27 | 江苏豪森药业集团有限公司 | 一种含利那洛肽或其盐的药物组合物及其制备方法 |
| CN113616616A (zh) * | 2021-09-07 | 2021-11-09 | 四川国为制药有限公司 | 一种利那洛肽胶囊制剂及其制备方法 |
| US20230106943A1 (en) * | 2021-09-17 | 2023-04-06 | Peptilogics, Inc. | Engineered antimicrobial peptides and usage thereof |
| CN114632141B (zh) * | 2022-04-19 | 2023-08-01 | 苏州中化药品工业有限公司 | 一种含利那洛肽的药物组合物、胶囊制剂及其制备方法 |
| CN116672309A (zh) * | 2023-07-26 | 2023-09-01 | 北京普诺旺康医药科技有限公司 | 干混悬药物组合物 |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH658973A5 (fr) | 1983-12-29 | 1986-12-31 | Nestle Sa | Produit aromatisant. |
| JPS6197229A (ja) * | 1984-10-18 | 1986-05-15 | Chugai Pharmaceut Co Ltd | 安定なエリトロポエチン製剤 |
| DE3729863A1 (de) * | 1987-09-05 | 1989-03-16 | Boehringer Mannheim Gmbh | Stabilisierte erythropoietin-lyophilisate |
| JPS649938A (en) | 1987-06-30 | 1989-01-13 | Agency Ind Science Techn | Oral ingestive composition |
| CA2028848A1 (en) | 1989-04-11 | 1990-10-12 | Tapan Audhya | Lyophilized peptide formulations |
| IT1240314B (it) | 1989-09-28 | 1993-12-07 | Immunobiology Research Institutes, Inc. | Formulazioni acquose stabilizzate di piccoli peptidi. |
| US5221495A (en) | 1990-04-13 | 1993-06-22 | Colgate-Palmolive Company | Enzyme stabilizing composition and stabilized enzyme containing built detergent compositions |
| US5451410A (en) * | 1993-04-22 | 1995-09-19 | Emisphere Technologies, Inc. | Modified amino acids for encapsulating active agents |
| US6284727B1 (en) * | 1993-04-07 | 2001-09-04 | Scios, Inc. | Prolonged delivery of peptides |
| US5681811A (en) | 1993-05-10 | 1997-10-28 | Protein Delivery, Inc. | Conjugation-stabilized therapeutic agent compositions, delivery and diagnostic formulations comprising same, and method of making and using the same |
| US5654278A (en) * | 1994-10-13 | 1997-08-05 | Novo Nordisk A/S | Composition and method comprising growth hormone and leucine |
| IL115592A (en) * | 1994-10-13 | 2000-07-26 | Novo Nordisk As | Stabilized pharmaceutical formulation comprising a growth hormone and leucine |
| US5593696A (en) * | 1994-11-21 | 1997-01-14 | Mcneil-Ppc, Inc. | Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders |
| US5904935A (en) | 1995-06-07 | 1999-05-18 | Alza Corporation | Peptide/protein suspending formulations |
| ZA965368B (en) * | 1995-07-14 | 1997-01-14 | Novo Nordisk As | A pharmaceutical formulation |
| US5932547A (en) | 1996-07-03 | 1999-08-03 | Alza Corporation | Non-aqueous polar aprotic peptide formulations |
| BR9710130A (pt) | 1996-07-03 | 1999-08-10 | Alza Corp | Formulações de peptídeos próticas não-aquosas |
| US5916582A (en) | 1996-07-03 | 1999-06-29 | Alza Corporation | Aqueous formulations of peptides |
| US20020151502A1 (en) * | 1997-10-09 | 2002-10-17 | Albert Sattin | Tri-peptides for neurological and neurobehavior applications |
| US6541606B2 (en) | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
| US6087478A (en) * | 1998-01-23 | 2000-07-11 | The Rockefeller University | Crystal of the N-terminal domain of a STAT protein and methods of use thereof |
| WO2000004880A1 (en) | 1998-07-23 | 2000-02-03 | Novo Nordisk A/S | A wet granulation method for preparing a stable pharmaceutical formulation |
| BR9913302A (pt) * | 1998-09-04 | 2002-09-24 | Gaplast Gmbh | Recipiente |
| CA2352389C (en) | 1998-11-27 | 2009-01-20 | Kanji Takada | An oral formulation for gastrointestinal drug delivery |
| US6734162B2 (en) | 2000-01-24 | 2004-05-11 | Minimed Inc. | Mixed buffer system for stabilizing polypeptide formulations |
| JP4711520B2 (ja) * | 2000-03-21 | 2011-06-29 | 日本ケミカルリサーチ株式会社 | 生理活性ペプチド含有粉末 |
| CA2413702A1 (en) | 2000-06-28 | 2002-01-03 | Teva Pharmaceuticals Industries Ltd. | Carvedilol |
| FR2811884B1 (fr) | 2000-07-21 | 2003-01-31 | Oreal | Utilisation en cosmetique de betainates d'amidon et composition les comprenant associes a au moins un agent benefique pour les matieres keratiniques |
| US6613308B2 (en) * | 2000-09-19 | 2003-09-02 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
| AU2001296389A1 (en) | 2000-09-29 | 2002-04-08 | Cognetix, Inc. | Stable peptide formulations |
| WO2002055101A2 (en) | 2000-12-21 | 2002-07-18 | Inhale Therapeutic Syst | Storage stable powder compositions of interleukin-4 receptor |
| CA2435835A1 (en) | 2001-02-02 | 2002-08-15 | Pharmacia Corporation | Uroguanylin and cyclooxygenase-2 inhibitor combinations for inhibition of intestinal cancer |
| GB0104371D0 (en) | 2001-02-22 | 2001-04-11 | Clariant Int Ltd | Color improving stabilizing compositions comprising leucine |
| US6573237B2 (en) | 2001-03-16 | 2003-06-03 | Eli Lilly And Company | Protein formulations |
| WO2002078683A1 (en) | 2001-03-29 | 2002-10-10 | Synergy Pharmaceuticals, Inc. | Guanylate cyclase receptor agonists for the treatment of tissue inflammation and carcinogenesis |
| WO2003014304A2 (en) | 2001-08-09 | 2003-02-20 | Doctor's Signature Sales And Marketing International Corp. [(Dba)] Life Force International | Protonic formulation |
| US20030104996A1 (en) | 2001-08-30 | 2003-06-05 | Tiansheng Li | L-methionine as a stabilizer for NESP/EPO in HSA-free formulations |
| US20040161776A1 (en) | 2001-10-23 | 2004-08-19 | Maddon Paul J. | PSMA formulations and uses thereof |
| PL370656A1 (en) * | 2001-12-21 | 2005-05-30 | Novo Nordisk A/S | Liquid composition of modified factor vii polypeptides |
| JP2003201256A (ja) | 2001-12-28 | 2003-07-18 | Hisamitsu Pharmaceut Co Inc | 大腸送達性経口医薬製剤、大腸癌治療用経口医薬製剤および大腸炎治療用経口医薬製剤 |
| DE10261126A1 (de) * | 2002-08-13 | 2004-03-04 | Aventis Behring Gmbh | Lagerungsstabile, flüssige Fibrinogen-Formulierung |
| CN1726012A (zh) | 2002-12-11 | 2006-01-25 | 辉瑞产品公司 | 活性物质在高脂肪环境中的控制释放 |
| US7304036B2 (en) * | 2003-01-28 | 2007-12-04 | Microbia, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US7371727B2 (en) * | 2003-01-28 | 2008-05-13 | Microbia, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| BR122018074353B8 (pt) * | 2003-01-28 | 2023-05-02 | Ironwood Pharmaceuticals Inc | composição farmacêutica, polipeptídeo e métodos para a produção dos mesmos |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| DK1638586T3 (da) | 2003-05-14 | 2008-06-23 | Indus Biotech Pvt Ltd | Synergistisk sammensætning til behandling af diabetes mellitus |
| CN1802171B (zh) * | 2003-06-10 | 2010-10-13 | 株式会社Lg生命科学 | 不包含血清白蛋白的人红细胞生成素的稳定水溶液 |
| US7494979B2 (en) | 2003-06-13 | 2009-02-24 | Ironwood Pharmaceuticals, Inc. | Method for treating congestive heart failure and other disorders |
| PL1644021T3 (pl) | 2003-06-13 | 2013-01-31 | Ironwood Pharmaceuticals Inc | Sposoby i kompozycje do leczenia zaburzeń żołądkowo-jelitowych |
| KR100560697B1 (ko) | 2003-08-06 | 2006-03-16 | 씨제이 주식회사 | 알부민을 함유하지 않는 에리스로포이에틴 제제 |
| DE102004011663B4 (de) * | 2004-03-10 | 2006-04-27 | Bioceuticals Arzneimittel Ag | Erythropoietin-Flüssigformulierung |
| WO2006071102A1 (en) | 2004-12-30 | 2006-07-06 | Dobeel Co., Ltd. | Spray-dried composition containing collectin family proteins or variants therof and process for preparing the same |
| EP1940441A4 (en) * | 2005-08-19 | 2010-01-27 | Ironwood Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR TREATING GASTROINTESTINAL DISORDERS |
| WO2007044375A2 (en) | 2005-10-06 | 2007-04-19 | Nastech Pharmaceutical Company Inc. | Pth formulations and methods of use |
| WO2007095716A1 (en) * | 2006-02-23 | 2007-08-30 | Iomedix Sleep International Srl | Compositions and methods for the induction and maintenance of quality sleep |
| US20090305993A1 (en) * | 2006-02-24 | 2009-12-10 | Ironwood Pharmaceuticals, Inc. | Methods and composition for the treatment of gastrointestinal disorders |
| ITMI20060629A1 (it) | 2006-03-31 | 2007-10-01 | Daniele Giovannone | Composizioni solide orali a base di s-adenosilmetionina e processo per il loro ottenimento |
| EP2078529B1 (en) | 2006-07-10 | 2014-12-10 | PBA3 Biomed GmbH | Antimicrobial peptides |
| PL2359808T3 (pl) | 2006-08-09 | 2013-10-31 | Intarcia Therapeutics Inc | Osmotyczne systemy dostawcze i zespoły tłokowe |
| EP2059260B1 (en) | 2006-08-31 | 2013-06-19 | Novartis AG | Pharmaceutical compositions comprising hGH for oral delivery |
| WO2008078189A2 (en) * | 2006-12-20 | 2008-07-03 | Bayer Healthcare Llc | Factor vii and viia compositions |
| EP2650303A1 (en) | 2007-02-26 | 2013-10-16 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of heart failure and other disorders |
| WO2008151257A2 (en) | 2007-06-04 | 2008-12-11 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| RS60101B1 (sr) | 2008-08-15 | 2020-05-29 | Ironwood Pharmaceuticals Inc | Formulacije koje sadrže linaklotid za oralnu primenu |
| US20120009225A1 (en) * | 2008-09-04 | 2012-01-12 | Ironwood Pharmaceuticals, Inc. | Stable Solid Formulation of Therapeutic Polypeptides Suitable for Oral Administration |
| WO2010027405A2 (en) * | 2008-09-04 | 2010-03-11 | Ironwood Pharmaceuticals, Inc. | Stable solid formulations of gc-c receptor agonist polypeptides suitable for oral administration |
| JP5964589B2 (ja) | 2008-12-03 | 2016-08-03 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼｃアゴニストの製剤およびその使用方法 |
| WO2011019819A1 (en) | 2009-08-12 | 2011-02-17 | Forest Laboratories Holdings Limited | Orally disintegrating compositions of linaclotide |
| US20130012454A1 (en) * | 2009-07-06 | 2013-01-10 | Ironwood Pharmaceuticals, Inc. | Orally Disintegrating Compositions of Linaclotide |
| US8748573B2 (en) * | 2009-08-06 | 2014-06-10 | Ironwood Pharmaceuticals, Inc. | Formulations comprising linaclotide |
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