JP2013501071A5 - - Google Patents

Info

Publication number

JP2013501071A5

JP2013501071A5 JP2012523941A JP2012523941A JP2013501071A5 JP 2013501071 A5 JP2013501071 A5 JP 2013501071A5 JP 2012523941 A JP2012523941 A JP 2012523941A JP 2012523941 A JP2012523941 A JP 2012523941A JP 2013501071 A5 JP2013501071 A5 JP 2013501071A5

Authority

JP

Japan

Prior art keywords

composition

stabilizing amount

linaclotide

item

composition according

Prior art date

2010-08-05

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.)

Withdrawn

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• 239000000203 mixture Substances 0.000 claims description 218
• 230000000087 stabilizing effect Effects 0.000 claims description 52
• 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 48
• 229960000812 linaclotide Drugs 0.000 claims description 48
• 108010024409 linaclotide Proteins 0.000 claims description 48
• 150000001768 cations Chemical class 0.000 claims description 37
• 229920000642 polymer Polymers 0.000 claims description 27
• 238000000034 method Methods 0.000 claims description 18
• 150000003141 primary amines Chemical class 0.000 claims description 17
• 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 16
• 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 16
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 16
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 15
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 15
• 229940024606 amino acid Drugs 0.000 claims description 15
• 235000001014 amino acid Nutrition 0.000 claims description 15
• 150000001413 amino acids Chemical class 0.000 claims description 15
• 239000011575 calcium Substances 0.000 claims description 14
• 239000011777 magnesium Substances 0.000 claims description 14
• 239000011701 zinc Substances 0.000 claims description 14
• 239000004372 Polyvinyl alcohol Substances 0.000 claims description 11
• 229920002451 polyvinyl alcohol Polymers 0.000 claims description 11
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 10
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 10
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 10
• 235000004279 alanine Nutrition 0.000 claims description 10
• 229960000310 isoleucine Drugs 0.000 claims description 10
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 10
• 229930182817 methionine Natural products 0.000 claims description 10
• 206010010774 Constipation Diseases 0.000 claims description 9
• 229910052751 metal Inorganic materials 0.000 claims description 8
• 239000002184 metal Substances 0.000 claims description 8
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 6
• 230000007062 hydrolysis Effects 0.000 claims description 6
• 238000006460 hydrolysis reaction Methods 0.000 claims description 6
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
• 230000003647 oxidation Effects 0.000 claims description 6
• 238000007254 oxidation reaction Methods 0.000 claims description 6
• 208000010643 digestive system disease Diseases 0.000 claims description 5
• 208000018685 gastrointestinal system disease Diseases 0.000 claims description 5
• 239000007864 aqueous solution Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 208000030053 Opioid-Induced Constipation Diseases 0.000 claims description 3
• 239000007853 buffer solution Substances 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 201000006549 dyspepsia Diseases 0.000 claims description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• 239000002775 capsule Substances 0.000 claims description 2
• 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 2
• 229910052749 magnesium Inorganic materials 0.000 claims description 2
• 239000011572 manganese Substances 0.000 claims description 2
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 239000011591 potassium Substances 0.000 claims description 2
• 229910052700 potassium Inorganic materials 0.000 claims description 2
• 150000003839 salts Chemical class 0.000 claims description 2
• 239000011734 sodium Substances 0.000 claims description 2
• 229910052708 sodium Inorganic materials 0.000 claims description 2
• 229910052725 zinc Inorganic materials 0.000 claims description 2
• 125000002091 cationic group Chemical group 0.000 claims 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
• -1 formaldehyde imine Chemical class 0.000 description 4