TW201136582A - Improved pharmaceutical compositions of aliskiren and methods of delivery - Google Patents

Improved pharmaceutical compositions of aliskiren and methods of delivery Download PDF

Info

Publication number: TW201136582A
Authority: TW; Taiwan
Prior art keywords: weight; pharmaceutical composition; sodium; fatty acid; combination
Prior art date: 2010-03-16

Application number

TW100108966A

Other languages

English (en)

Chinese (zh)

Inventor

Paul Salama

Irina Karmeli

Shmuel Tuvia

Karen Marom

Oshrat Harush-Frenkel

Sam Rebello

Original Assignee

Novartis Ag

Priority date (The priority date 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 date listed.)

2010-03-16

Filing date

2011-03-16

Publication date

2011-11-01

2011-03-16 Application filed by Novartis Ag filed Critical Novartis Ag

2011-11-01 Publication of TW201136582A publication Critical patent/TW201136582A/zh

Links

238000000034 method Methods 0.000 title claims abstract description 109
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 107
UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical group COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 title claims abstract description 95
229960004601 aliskiren Drugs 0.000 title claims abstract description 95
238000012384 transportation and delivery Methods 0.000 title abstract description 9
239000000203 mixture Substances 0.000 claims abstract description 375
239000007787 solid Substances 0.000 claims abstract description 126
230000002209 hydrophobic effect Effects 0.000 claims abstract description 112
229920000642 polymer Polymers 0.000 claims abstract description 76
239000004094 surface-active agent Substances 0.000 claims abstract description 75
150000003839 salts Chemical class 0.000 claims abstract description 63
239000011159 matrix material Substances 0.000 claims abstract description 37
239000000725 suspension Substances 0.000 claims abstract description 36
239000002775 capsule Substances 0.000 claims abstract description 28
201000010099 disease Diseases 0.000 claims abstract 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
-1 medium chain fatty acid salt Chemical class 0.000 claims description 160
239000003814 drug Substances 0.000 claims description 84
229940124597 therapeutic agent Drugs 0.000 claims description 74
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 58
235000014113 dietary fatty acids Nutrition 0.000 claims description 49
239000000194 fatty acid Substances 0.000 claims description 49
229930195729 fatty acid Natural products 0.000 claims description 49
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 48
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 41
BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 claims description 40
239000003381 stabilizer Substances 0.000 claims description 40
239000002245 particle Substances 0.000 claims description 39
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
239000000843 powder Substances 0.000 claims description 36
229910052751 metal Inorganic materials 0.000 claims description 31
239000002184 metal Substances 0.000 claims description 31
239000004475 Arginine Substances 0.000 claims description 30
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 30
239000004372 Polyvinyl alcohol Substances 0.000 claims description 29
229920002451 polyvinyl alcohol Polymers 0.000 claims description 29
229940068984 polyvinyl alcohol Drugs 0.000 claims description 29
235000019422 polyvinyl alcohol Nutrition 0.000 claims description 29
229920002125 Sokalan® Polymers 0.000 claims description 28
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 28
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 28
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 27
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 27
239000001267 polyvinylpyrrolidone Substances 0.000 claims description 27
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 26
235000010445 lecithin Nutrition 0.000 claims description 26
239000000787 lecithin Substances 0.000 claims description 26
229940067606 lecithin Drugs 0.000 claims description 26
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 26
239000002552 dosage form Substances 0.000 claims description 25
235000011187 glycerol Nutrition 0.000 claims description 23
VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical group CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 claims description 22
235000001014 amino acid Nutrition 0.000 claims description 21
229940024606 amino acid Drugs 0.000 claims description 21
150000001413 amino acids Chemical group 0.000 claims description 21
239000006186 oral dosage form Substances 0.000 claims description 21
JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 claims description 21
239000003833 bile salt Substances 0.000 claims description 20
238000002360 preparation method Methods 0.000 claims description 20
229940093609 tricaprylin Drugs 0.000 claims description 20
229960002446 octanoic acid Drugs 0.000 claims description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 18
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 claims description 17
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 17
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims description 17
238000005469 granulation Methods 0.000 claims description 17
230000003179 granulation Effects 0.000 claims description 17
239000003112 inhibitor Substances 0.000 claims description 16
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 16
229920000053 polysorbate 80 Polymers 0.000 claims description 16
206010020772 Hypertension Diseases 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 15
OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 15
239000008187 granular material Substances 0.000 claims description 15
GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 claims description 15
239000011734 sodium Substances 0.000 claims description 15
229910052708 sodium Inorganic materials 0.000 claims description 15
229940083542 sodium Drugs 0.000 claims description 15
239000000052 vinegar Substances 0.000 claims description 15
235000021419 vinegar Nutrition 0.000 claims description 15
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 14
239000000243 solution Substances 0.000 claims description 14
229960001631 carbomer Drugs 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 13
238000004108 freeze drying Methods 0.000 claims description 13
238000001694 spray drying Methods 0.000 claims description 13
LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical group OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 11
206010019280 Heart failures Diseases 0.000 claims description 11
229960000583 acetic acid Drugs 0.000 claims description 11
235000011054 acetic acid Nutrition 0.000 claims description 11
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 11
238000001035 drying Methods 0.000 claims description 11
150000004665 fatty acids Chemical class 0.000 claims description 11
229920001983 poloxamer Polymers 0.000 claims description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
102000003729 Neprilysin Human genes 0.000 claims description 10
108090000028 Neprilysin Proteins 0.000 claims description 10
UYXTWWCETRIEDR-UHFFFAOYSA-N Tributyrin Chemical compound CCCC(=O)OCC(OC(=O)CCC)COC(=O)CCC UYXTWWCETRIEDR-UHFFFAOYSA-N 0.000 claims description 10
206010012601 diabetes mellitus Diseases 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
239000001509 sodium citrate Substances 0.000 claims description 10
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 10
239000004246 zinc acetate Substances 0.000 claims description 10
235000013904 zinc acetate Nutrition 0.000 claims description 10
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 9
206010001580 Albuminuria Diseases 0.000 claims description 9
201000001320 Atherosclerosis Diseases 0.000 claims description 9
206010007559 Cardiac failure congestive Diseases 0.000 claims description 9
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 9
239000004471 Glycine Substances 0.000 claims description 9
206010019233 Headaches Diseases 0.000 claims description 9
208000033679 diabetic kidney disease Diseases 0.000 claims description 9
231100000869 headache Toxicity 0.000 claims description 9
208000010125 myocardial infarction Diseases 0.000 claims description 9
239000000600 sorbitol Substances 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
206010002383 Angina Pectoris Diseases 0.000 claims description 8
206010007558 Cardiac failure chronic Diseases 0.000 claims description 8
208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims description 8
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 8
208000018262 Peripheral vascular disease Diseases 0.000 claims description 8
229920001214 Polysorbate 60 Polymers 0.000 claims description 8
208000001647 Renal Insufficiency Diseases 0.000 claims description 8
IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims description 8
208000006011 Stroke Diseases 0.000 claims description 8
239000003599 detergent Substances 0.000 claims description 8
201000006370 kidney failure Diseases 0.000 claims description 8
239000011654 magnesium acetate Substances 0.000 claims description 8
229940069446 magnesium acetate Drugs 0.000 claims description 8
235000011285 magnesium acetate Nutrition 0.000 claims description 8
235000000346 sugar Nutrition 0.000 claims description 8
208000032781 Diabetic cardiomyopathy Diseases 0.000 claims description 7
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 7
239000002202 Polyethylene glycol Substances 0.000 claims description 7
235000010443 alginic acid Nutrition 0.000 claims description 7
229920000615 alginic acid Polymers 0.000 claims description 7
239000007864 aqueous solution Substances 0.000 claims description 7
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 7
239000001639 calcium acetate Substances 0.000 claims description 7
235000011092 calcium acetate Nutrition 0.000 claims description 7
229960005147 calcium acetate Drugs 0.000 claims description 7
208000010877 cognitive disease Diseases 0.000 claims description 7
239000002934 diuretic Substances 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
239000000499 gel Substances 0.000 claims description 7
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 7
239000000463 material Substances 0.000 claims description 7
229920001223 polyethylene glycol Polymers 0.000 claims description 7
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
125000001931 aliphatic group Chemical group 0.000 claims description 6
159000000007 calcium salts Chemical class 0.000 claims description 6
230000009977 dual effect Effects 0.000 claims description 6
239000002563 ionic surfactant Substances 0.000 claims description 6
239000012528 membrane Substances 0.000 claims description 6
239000002736 nonionic surfactant Substances 0.000 claims description 6
229920000058 polyacrylate Polymers 0.000 claims description 6
239000011591 potassium Substances 0.000 claims description 6
229910052700 potassium Inorganic materials 0.000 claims description 6
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 claims description 6
150000003751 zinc Chemical class 0.000 claims description 6
WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 claims description 5
XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 claims description 5
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 5
241000283690 Bos taurus Species 0.000 claims description 5
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 5
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 5
229940072056 alginate Drugs 0.000 claims description 5
239000004359 castor oil Substances 0.000 claims description 5
235000019438 castor oil Nutrition 0.000 claims description 5
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 5
FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 claims description 5
229910052744 lithium Inorganic materials 0.000 claims description 5
159000000003 magnesium salts Chemical class 0.000 claims description 5
239000002480 mineral oil Substances 0.000 claims description 5
229960000502 poloxamer Drugs 0.000 claims description 5
239000002464 receptor antagonist Substances 0.000 claims description 5
229940044551 receptor antagonist Drugs 0.000 claims description 5
UDWXLZLRRVQONG-UHFFFAOYSA-M sodium hexanoate Chemical group [Na+].CCCCCC([O-])=O UDWXLZLRRVQONG-UHFFFAOYSA-M 0.000 claims description 5
NMTDPTPUELYEPL-UHFFFAOYSA-M sodium;heptanoate Chemical compound [Na+].CCCCCCC([O-])=O NMTDPTPUELYEPL-UHFFFAOYSA-M 0.000 claims description 5
229940035044 sorbitan monolaurate Drugs 0.000 claims description 5
229940031953 sorbitan monopalmitate Drugs 0.000 claims description 5
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 4
ARIWANIATODDMH-AWEZNQCLSA-N 1-lauroyl-sn-glycerol Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)CO ARIWANIATODDMH-AWEZNQCLSA-N 0.000 claims description 4
RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 claims description 4
KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 claims description 4
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 4
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
LKUNXBRZDFMZOK-GFCCVEGCSA-N Capric acid monoglyceride Natural products CCCCCCCCCC(=O)OC[C@H](O)CO LKUNXBRZDFMZOK-GFCCVEGCSA-N 0.000 claims description 4
239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 claims description 4
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 4
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 4
239000004698 Polyethylene Substances 0.000 claims description 4
150000001491 aromatic compounds Chemical class 0.000 claims description 4
229960001230 asparagine Drugs 0.000 claims description 4
235000009582 asparagine Nutrition 0.000 claims description 4
235000003704 aspartic acid Nutrition 0.000 claims description 4
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 4
230000036772 blood pressure Effects 0.000 claims description 4
239000001110 calcium chloride Substances 0.000 claims description 4
235000011148 calcium chloride Nutrition 0.000 claims description 4
229910001628 calcium chloride Inorganic materials 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
229960003964 deoxycholic acid Drugs 0.000 claims description 4
PPXUHEORWJQRHJ-UHFFFAOYSA-N ethyl isovalerate Chemical compound CCOC(=O)CC(C)C PPXUHEORWJQRHJ-UHFFFAOYSA-N 0.000 claims description 4
235000019197 fats Nutrition 0.000 claims description 4
RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 claims description 4
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 4
229940075507 glyceryl monostearate Drugs 0.000 claims description 4
229940014041 hyaluronate Drugs 0.000 claims description 4
229910001629 magnesium chloride Inorganic materials 0.000 claims description 4
235000011147 magnesium chloride Nutrition 0.000 claims description 4
235000010446 mineral oil Nutrition 0.000 claims description 4
239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
239000003921 oil Substances 0.000 claims description 4
235000019198 oils Nutrition 0.000 claims description 4
229920000573 polyethylene Polymers 0.000 claims description 4
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 4
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 4
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 4
LKUNXBRZDFMZOK-UHFFFAOYSA-N rac-1-monodecanoylglycerol Chemical compound CCCCCCCCCC(=O)OCC(O)CO LKUNXBRZDFMZOK-UHFFFAOYSA-N 0.000 claims description 4
239000008159 sesame oil Substances 0.000 claims description 4
235000011803 sesame oil Nutrition 0.000 claims description 4
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 claims description 4
OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 claims description 4
ZOOPHYLANWVUDY-UHFFFAOYSA-M sodium;undecanoate Chemical compound [Na+].CCCCCCCCCCC([O-])=O ZOOPHYLANWVUDY-UHFFFAOYSA-M 0.000 claims description 4
235000011069 sorbitan monooleate Nutrition 0.000 claims description 4
239000001593 sorbitan monooleate Substances 0.000 claims description 4
229940035049 sorbitan monooleate Drugs 0.000 claims description 4
235000011071 sorbitan monopalmitate Nutrition 0.000 claims description 4
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229940069328 povidone Drugs 0.000 description 1
229960002965 pravastatin Drugs 0.000 description 1
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239000000651 prodrug Substances 0.000 description 1
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
229960003401 ramipril Drugs 0.000 description 1
HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
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229950006241 saprisartan Drugs 0.000 description 1
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PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
239000000779 smoke Substances 0.000 description 1
239000004317 sodium nitrate Substances 0.000 description 1
235000010344 sodium nitrate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
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159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
MDTNUYUCUYPIHE-UHFFFAOYSA-N sodium;(4-chloro-3-methyl-1,2-oxazol-5-yl)-[2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophen-3-yl]sulfonylazanide Chemical compound [Na+].CC1=NOC([N-]S(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl MDTNUYUCUYPIHE-UHFFFAOYSA-N 0.000 description 1
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HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
108700035424 spirapril Proteins 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
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239000007858 starting material Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
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TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 1
229960005187 telmisartan Drugs 0.000 description 1
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FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
230000002277 temperature effect Effects 0.000 description 1
238000010998 test method Methods 0.000 description 1
229950000584 tezosentan Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
239000001585 thymus vulgaris Substances 0.000 description 1
210000001578 tight junction Anatomy 0.000 description 1
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238000004448 titration Methods 0.000 description 1
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230000002588 toxic effect Effects 0.000 description 1
229960002051 trandolapril Drugs 0.000 description 1
CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
229940117013 triethanolamine oleate Drugs 0.000 description 1
125000005457 triglyceride group Chemical group 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
230000002792 vascular Effects 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1
229920003170 water-soluble synthetic polymer Polymers 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
150000003752 zinc compounds Chemical class 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1

Classifications

- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oil, Petroleum & Natural Gas (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Inorganic Chemistry (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

TW100108966A 2010-03-16 2011-03-16 Improved pharmaceutical compositions of aliskiren and methods of delivery TW201136582A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US31439810P	2010-03-16	2010-03-16

Publications (1)

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TW201136582A true TW201136582A (en)	2011-11-01

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TW100108966A TW201136582A (en)	2010-03-16	2011-03-16	Improved pharmaceutical compositions of aliskiren and methods of delivery

Country Status (3)

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AR (1)	AR080683A1 (fr)
TW (1)	TW201136582A (fr)
WO (1)	WO2011116115A1 (fr)

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Publication number	Priority date	Publication date	Assignee	Title
US20150283163A1 (en) *	2014-04-04	2015-10-08	Organic Medical Ventures, L.L.C.	Muscle treatment composition and method making same

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US5508272A (en)	1993-06-15	1996-04-16	Bristol-Myers Squibb Company	Compounds containing a fused bicycle ring and processes therefor
CA2169737C (fr)	1993-08-18	2003-04-15	Kiyofumi Ishikawa	Derives heteroatomiques du cyclopentene a noyaux condenses, antagonistes de l'endotheline
MY119161A (en)	1994-04-18	2005-04-30	Novartis Ag	Delta-amino-gamma-hydroxy-omega-aryl-alkanoic acid amides with enzyme especially renin inhibiting activities
US5612359A (en)	1994-08-26	1997-03-18	Bristol-Myers Squibb Company	Substituted biphenyl isoxazole sulfonamides
RU2172735C2 (ru)	1995-12-20	2001-08-27	Яманоути Фармасьютикал Ко., Лтд.	Арилэтенсульфонамидные производные и фармацевтическая композиция
IT1277737B1 (it)	1995-12-28	1997-11-12	Zambon Spa	Derivati tiolici ad attivita' inibitrice delle metallopeptidasi
WO1997027314A1 (fr)	1996-01-23	1997-07-31	Shionogi & Co., Ltd.	Processus de production d'analogues d'acide oleanolique par la culture de racine pileuse
DE69733557T2 (de)	1996-04-04	2005-11-03	Banyu Pharmaceutical Co., Ltd.	Endothelin-antagonisten zur behandlung von herzversagen
PE20050596A1 (es) *	2003-12-19	2005-10-18	Novartis Ag	Microemulsion que comprende un inhibidor renina
US20100247645A1 (en) *	2007-09-28	2010-09-30	Catherine Curdy	Pharmaceutical combination of aliskiren and valsartan
CN101808630A (zh)	2007-09-28	2010-08-18	诺瓦提斯公司	阿利吉仑的盖仑制剂
AU2008309058B2 (en) *	2007-09-28	2012-08-09	Novartis Ag	Galenical formulations of Aliskiren and Valsartan

2011
- 2011-03-16 AR ARP110100850A patent/AR080683A1/es unknown
- 2011-03-16 WO PCT/US2011/028698 patent/WO2011116115A1/fr not_active Ceased
- 2011-03-16 TW TW100108966A patent/TW201136582A/zh unknown

Also Published As

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WO2011116115A1 (fr)	2011-09-22
AR080683A1 (es)	2012-05-02

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AU2007262493A1 (en)	2007-12-27	Pharmaceutical composition for oral administration
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