HUE034836T2 - Protonkötõ polimerek orális beadásra - Google Patents
Protonkötõ polimerek orális beadásra Download PDFInfo
- Publication number
- HUE034836T2 HUE034836T2 HUE14742001A HUE14742001A HUE034836T2 HU E034836 T2 HUE034836 T2 HU E034836T2 HU E14742001 A HUE14742001 A HU E14742001A HU E14742001 A HUE14742001 A HU E14742001A HU E034836 T2 HUE034836 T2 HU E034836T2
- Authority
- HU
- Hungary
- Prior art keywords
- polymer
- amine
- chloride
- pharmaceutical composition
- mmol
- Prior art date
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- 229920000642 polymer Polymers 0.000 title claims description 507
- 150000001412 amines Chemical class 0.000 claims description 366
- 239000001257 hydrogen Substances 0.000 claims description 187
- 229910052739 hydrogen Inorganic materials 0.000 claims description 187
- 239000008194 pharmaceutical composition Substances 0.000 claims description 184
- 150000002431 hydrogen Chemical class 0.000 claims description 146
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 122
- 208000010444 Acidosis Diseases 0.000 claims description 104
- 229910001868 water Inorganic materials 0.000 claims description 102
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical group OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 100
- 239000000872 buffer Substances 0.000 claims description 95
- 206010027417 Metabolic acidosis Diseases 0.000 claims description 82
- -1 amine amine Chemical class 0.000 claims description 78
- 210000002966 serum Anatomy 0.000 claims description 70
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 65
- 230000008961 swelling Effects 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 238000000034 method Methods 0.000 claims description 62
- 238000003556 assay Methods 0.000 claims description 60
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims description 55
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 40
- 125000001188 haloalkyl group Chemical group 0.000 claims description 39
- 238000006467 substitution reaction Methods 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 35
- 125000003342 alkenyl group Chemical group 0.000 claims description 32
- 229920002554 vinyl polymer Polymers 0.000 claims description 27
- 210000000813 small intestine Anatomy 0.000 claims description 23
- 239000011734 sodium Substances 0.000 claims description 23
- 229910052708 sodium Inorganic materials 0.000 claims description 23
- 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 22
- 230000001684 chronic effect Effects 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 230000007950 acidosis Effects 0.000 claims description 19
- 208000026545 acidosis disease Diseases 0.000 claims description 19
- 239000008367 deionised water Substances 0.000 claims description 17
- 229910021641 deionized water Inorganic materials 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 13
- 239000011591 potassium Substances 0.000 claims description 12
- 229910052700 potassium Inorganic materials 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 239000003431 cross linking reagent Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 238000013459 approach Methods 0.000 claims description 7
- 210000002784 stomach Anatomy 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- 239000008188 pellet Substances 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 230000001079 digestive effect Effects 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 239000002207 metabolite Substances 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 206010057190 Respiratory tract infections Diseases 0.000 claims 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims 1
- 241000192700 Cyanobacteria Species 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- 206010028720 Nasal abscess Diseases 0.000 claims 1
- 101150105461 Stim1 gene Proteins 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 238000005054 agglomeration Methods 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 230000001153 anti-wrinkle effect Effects 0.000 claims 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims 1
- 239000004327 boric acid Substances 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 239000002738 chelating agent Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 230000008021 deposition Effects 0.000 claims 1
- 229930195712 glutamate Natural products 0.000 claims 1
- 239000004816 latex Substances 0.000 claims 1
- 229920000126 latex Polymers 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 230000037361 pathway Effects 0.000 claims 1
- 239000002356 single layer Substances 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 226
- 125000001183 hydrocarbyl group Chemical group 0.000 description 145
- 150000002500 ions Chemical class 0.000 description 91
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
- 239000004971 Cross linker Substances 0.000 description 81
- 125000004103 aminoalkyl group Chemical group 0.000 description 74
- 125000001931 aliphatic group Chemical group 0.000 description 73
- 150000001450 anions Chemical class 0.000 description 71
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 64
- 238000006116 polymerization reaction Methods 0.000 description 62
- 239000011324 bead Substances 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 229910019142 PO4 Inorganic materials 0.000 description 53
- 239000010452 phosphate Substances 0.000 description 53
- 238000004132 cross linking Methods 0.000 description 51
- 239000000243 solution Substances 0.000 description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- 208000020832 chronic kidney disease Diseases 0.000 description 48
- 239000000178 monomer Substances 0.000 description 48
- 230000002452 interceptive effect Effects 0.000 description 43
- 125000003277 amino group Chemical group 0.000 description 42
- 239000000499 gel Substances 0.000 description 42
- 229910052757 nitrogen Inorganic materials 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 125000004432 carbon atom Chemical group C* 0.000 description 37
- 210000003734 kidney Anatomy 0.000 description 36
- 230000014759 maintenance of location Effects 0.000 description 32
- 238000005406 washing Methods 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- 125000000623 heterocyclic group Chemical group 0.000 description 31
- 238000010526 radical polymerization reaction Methods 0.000 description 31
- 230000002496 gastric effect Effects 0.000 description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- 239000012530 fluid Substances 0.000 description 24
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 21
- 230000001965 increasing effect Effects 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 229910000162 sodium phosphate Inorganic materials 0.000 description 21
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 20
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 20
- 239000011550 stock solution Substances 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- 239000002585 base Substances 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 229910002092 carbon dioxide Inorganic materials 0.000 description 17
- 201000010099 disease Diseases 0.000 description 17
- UHTZABZWCSJMDY-UHFFFAOYSA-N 2-(chloromethyl)oxirane;n,n,n',n'-tetrakis(3-aminopropyl)butane-1,4-diamine Chemical compound ClCC1CO1.NCCCN(CCCN)CCCCN(CCCN)CCCN UHTZABZWCSJMDY-UHFFFAOYSA-N 0.000 description 16
- 241000282414 Homo sapiens Species 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 16
- 239000008280 blood Substances 0.000 description 16
- 210000001072 colon Anatomy 0.000 description 16
- 229920006037 cross link polymer Polymers 0.000 description 16
- 230000007423 decrease Effects 0.000 description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 16
- WBWWGRHZICKQGZ-HZAMXZRMSA-M taurocholate 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-M 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 229950007940 bixalomer Drugs 0.000 description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 description 15
- 201000010384 renal tubular acidosis Diseases 0.000 description 15
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 14
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 14
- 238000011534 incubation Methods 0.000 description 14
- 239000002245 particle Substances 0.000 description 14
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000003999 initiator Substances 0.000 description 12
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- 150000004666 short chain fatty acids Chemical class 0.000 description 12
- 235000021391 short chain fatty acids Nutrition 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
- LXEKPEMOWBOYRF-UHFFFAOYSA-N [2-[(1-azaniumyl-1-imino-2-methylpropan-2-yl)diazenyl]-2-methylpropanimidoyl]azanium;dichloride Chemical compound Cl.Cl.NC(=N)C(C)(C)N=NC(C)(C)C(N)=N LXEKPEMOWBOYRF-UHFFFAOYSA-N 0.000 description 11
- 125000003282 alkyl amino group Chemical group 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 11
- 229960003975 potassium Drugs 0.000 description 11
- 239000008366 buffered solution Substances 0.000 description 10
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 10
- 210000001035 gastrointestinal tract Anatomy 0.000 description 10
- 125000004404 heteroalkyl group Chemical group 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 206010019280 Heart failures Diseases 0.000 description 9
- 208000002682 Hyperkalemia Diseases 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 9
- 239000003513 alkali Substances 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 238000004364 calculation method Methods 0.000 description 9
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- 125000004043 oxo group Chemical group O=* 0.000 description 9
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- 229940085991 phosphate ion Drugs 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 230000002459 sustained effect Effects 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000003613 bile acid Substances 0.000 description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 8
- 239000003792 electrolyte Substances 0.000 description 8
- 201000000523 end stage renal failure Diseases 0.000 description 8
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 8
- 208000006443 lactic acidosis Diseases 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
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- 229910052717 sulfur Inorganic materials 0.000 description 8
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 8
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 7
- 206010020944 Hypoaldosteronism Diseases 0.000 description 7
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 7
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 7
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- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 6
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- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 6
- 208000020131 Acid-base disease Diseases 0.000 description 6
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 6
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000005642 Oleic acid Substances 0.000 description 6
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- LDPIQRWHBLWKPR-UHFFFAOYSA-N aminoboronic acid Chemical compound NB(O)O LDPIQRWHBLWKPR-UHFFFAOYSA-N 0.000 description 6
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
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- 150000004665 fatty acids Chemical class 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 6
- 239000001294 propane Substances 0.000 description 6
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- 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 description 6
- 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 description 6
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- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 5
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- 150000007523 nucleic acids Chemical class 0.000 description 1
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- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- ZNZJJSYHZBXQSM-UHFFFAOYSA-N propane-2,2-diamine Chemical compound CC(C)(N)N ZNZJJSYHZBXQSM-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- NHARPDSAXCBDDR-UHFFFAOYSA-N propyl 2-methylprop-2-enoate Chemical compound CCCOC(=O)C(C)=C NHARPDSAXCBDDR-UHFFFAOYSA-N 0.000 description 1
- PNXMTCDJUBJHQJ-UHFFFAOYSA-N propyl prop-2-enoate Chemical compound CCCOC(=O)C=C PNXMTCDJUBJHQJ-UHFFFAOYSA-N 0.000 description 1
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- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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Classifications
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- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a single or double bond to nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/024—Polyamines containing oxygen in the form of ether bonds in the main chain
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
- G01N2001/4083—Concentrating samples by other techniques involving separation of suspended solids sedimentation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
- G01N2001/4088—Concentrating samples by other techniques involving separation of suspended solids filtration
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Claims (11)
- PKurosKôrôPOUMrRTh or y iv rfada<r\ .1. Gyógyászati készítmény metaboiikus acidózis s gyógyászati készítmény orális beadása általi kezelése* rs: &a-ö|gáió: eHá^sóasi tóetáfté «PaMtâP»*, ahoi & ;jPâ*^kÂ^téÂMtôt arampbihtsérl iáiSAltliaz, amely t képlet szerisi -mont 1¾¾¾¾¾ahol :Ët, R* és Ryjotóáse is :#PÄi:lt§gs«Ä -»sgia,: ÄroksrtÄ hogy Rj : % és R.; legalább egyike hidrogéntől különbözik, a áezzadáiá aránya ioncserélt vízben 5 vagy kisebb, a remi« 0,35:1 môlarÉJÿbaakóü as kloridionokat és m intérferáló imokM, iMpttsSÄ $psj€Ér^seoö^ibm.jterfeÄl^feö'P'lt^ 31 mM klorMkotteesb· íáeiőji és 2(Hnj^';:f0SÄk^^t«^ 5,S^flf»a;'ps#§r«fe.^ib
- 2. Az \< igénypoot szerinti gyógyászai készítmény &?, ott meghatározott alkalmazásra, aboi a térhálós!· son aöllspolítnérégyensiiyí duzzadást atâtip ifesesgîéit vízben 4 vagy kisebb, vágy 3 vagy kisebb, vagy 2 vagy kisebb, vagy RS vagy kisebb, vagy 1 vagy kisebb. J, ÁZ előző ahol Rí, R, és R; jelentése is t^biiii'^gbtlbhMdmgpi, slMpsikerbk alii,. vbbl, ail, amlboaíMl,: alkäKöi, haloaikil. hidrostaikif, éter*, hcterosril vagy heíersíbikbís, Ibiiévé azonban, begy iR;, By és % egyike sess: bîibo~ géo, vagy közelebbről az előző igénypontok bármelyike szerinti gyógyászati készíRbény az ob meghaíárózptt alkalmazásra, ahol R;, 1\> és Ki jelentése a ióbbitii ibggsnleiii! biirogbíi, sbfás vagy heíeroaííMSí;fbit#Vö ban, bogy R;, R; és Rj legalább egyikének jeien-ése .hiótogéoiői különbözik.
- 4, Az ívd. Igénypontok bármelyike szerion gyágyászabikészibiiéiiyvaz olt njépináxözoti blkálmtiZásm, ahol a térhálósított snnmpobmer tartalmaz 1 a képletszerinti amint, és a térhálósított aminpoünmr H képlet szeműi amis gyökös poiitnerizáoíójával előállítón. $. A 4- Igép^pö^ ,u«Iip#aP^il:Älra8Äfäp»l.}öl %;#s IsjéP«« mm RlbbMl íágiotíenü Mdtogén, atkjl, ÄöiLalBh visib aril, tmnnoälMi, äSkaoet, Mioalki, bitfeoxiaikil, éter., holeroaril vagy hetoroeiklas, vagy közelebbről a 4. Igénypont szsritâÎ^ôf^ézrM-kesMtmény·,. ebei R.; és R:; jelentése a többitől tliggetienlll hidrogén, alilaa vagy hetero&lilas. é Az: 1-3. igénypontok bármelyike szerinti gyógyászati készítmény az ott meghalározott alkalmazásra, ahol a. térhálósított asnispolimer tartalmaz ih képletSiKmsîi wêM* ás » am}«p<Äet Ib képkt sxaratl arvà«: poitfunkiUmdlts keres#^^«P>*t*$ vd& $g$â$t*t$i$| poJtnwméciôtàv*! el6éQ!gâ&;: &hul !<U és R< jeîesfése s tôbs>îti>i iUggetleahl hidrogén, hidrakarbll vagy sxasbssdtoák hidyoaadnl, R* jelentése sIMs bs Ríi! és jelpiése 8 ibbbltsHIhfpptionhi $0¾ fi A 6, igêhy^bbi sáerhéi gyágpsaati feMifoMíiy át ottm«ghäÄfeoi: Slkiy»^*»&* es fcs MáM* mm a;lÖbbtl#l fhggeíl«g§l hlhrogén, teilten sgénhlápgén, telítetten alifite, arü, heteroas'il hoferosskA vagy *ΜΙ* eUen heteroalifás, vagy kdaeiebbrö! a A sgééypösrs^M gyógyászai késahsnény, ah‘>l ¥.·. és Rs jelentése a #bbiRli föggesfesxki hixímgöíi, alkll. alkeaik síül, vkók sdJ, amínoaikil* allseoí;, hsOoaiä<*b hteroxiatkil. von-.·. éteiéhsstii vagy hesertîeikki::, vagy köaelebbtdl a 6. igénypont ssaíiMi gségyás^? készítmény, ahoi R» «s 8$ jétentéss; 3 Rbbsiöl ftjg|í«ieökl|pt^É% alls! vagy aîmsoÂh,
- 8. As dőzö igénypontok bánndyíke saedotí gyégyásasi kéésIhïRéy as: OR iaköi a térhálósított ammpolimet ttntahßftz le képiéisaeHatramfcí, ahol RT jelentése hidrogén, aillés vagy hetórosbtas, és R, jelenté» alliäs vagy heteroakiss.
- 9. Aa ΙΆ igénypontok bársoelylke sasoinu gyógyász « készítmény ázott meghatározott atk&sma?Ás?a* «ΜΙ s térhálósított atniopohmet tarlahnaz 2 képletszerinti amiah ahol m és h|eieni«ké δ tiÄhöi ii^afeüi ne?« negativ <g«;:s szánt, Rsa« R»* R*> és R4f, lekötése a többitől iiiggefloíiül hiárogéo, hidrokarbi! vagy sznbsztitnáh hldroknrbsi, X: jelentéseX: jelentése iódroh;oi>il vagy saobs:RlioP:bhio>k&roMs mbU<.g>^ Mi jeb'ssesa a vhbaCh fôggeitenül ηΟοχηο XsertAaiPk síéhsebtoP no^Uitel buho^s saxo gisihö, és a jélenAsé 50 A o, igénypont szerinti gyógyászati készítmény %m·· és R*·, leiemése s többitől függetlenül hidrogén. ail Ois, st'hí; zjé!i»íék«:&Äbl* iOS föfptfenOl #*$ és ο jóíéatésé Ο vagy i, és/vagyairskXyjeloníése stfe vagy fcsteí^m ft. a 9, v&gy: tői !j|éöypouf szeíiotl gyégyta®' Rtetaáity sz ott megtett^«#: jelentése I .és Xi ,..iekntésí hidrogén. ahibs n A; 1-3 igvnypomok bármelyike szénát i gyógyászati készítmény az ott meginaáfozo« rdiaímazásra, ahota térhálósított ammpolhner ïamlimz 2a képiét mám atomkahol m és 0 jelentése s többitől iöggsílenül nem negatívegész szánk mindegyik RÏS jélésstésé aláOhltói iSpstknül hidíögé«,· hidroisÄl, héteröalills vagy keterearsk Rj: and R;;î jelentése a többitől töggeitöttöl hidrogén vagy interoahítö. R.: ; jelentése hidfögésí, sgutehuálí iïidW^iivâp^Â^bÔ». X; jelentéseXj jelentése nihil vagy szuhsztimaít hídipkarbij, mindegyik R,? jelentése a többitől fögpieftiľ^l¾^¾íi^i5 '&m$m smittöálRii bórsavhklógétk és >; j:éietik‘;;s nem negatív szám; 13. A 112, Igénypont szerinti gyógyászati készítmény asi ötl meghatätoMti: sikáteszáss'íi, lentése a többitől függetlenül 0-3 és n jelentése ö vagy 1. til A Ä· vagy 13. Igénypont szerinti gyógyászati készítmény m olt: meghatározott áfeltstázasbk: ahol Rj : jölemése a többhől fô^etis«Bîlhidmg%aiJ^.amiàôdiki| haloalkil vagy hetsh*anl;,.:% jÂi®âé.:» többitől Rlggöíiesül hidrogén vagy Meroaílfe, és 1% jelentése mórogérg aillas,, aril,istszoah&s vagy hetero-stáb vagy kfclMI a 1:2. vagy .13, ^Igénypont szerinti gyógyászati készítmény, ahol tnintlegyík R.» jelentése hidrogén, aillis.. smlnoalhíi vagy :hs|oslkí| :R2, és 1½ jelenése hidrogén vagy annrmáiki| és &}, jelentése híd-rögén, alitas vagy hoteroálifás. IS. Az;R3. ígjÉtypön«á% bite§!yiü: szer inti gyógyászati készítmény az óit meghatározott alkaistazásm, ahol a térhálósított amlhpőiimgr2b képieméimegfeleld amint ttmeimsz, ahol ».és b jelentése ä többitö! »ggeÖenCll nem gágsílv egész $zâre, OÄdogytk: % jelentisé s tőül! RiggetienO! hidrogén, ^b&a&ifí htdÄpi vagy hldrokarblk R;>:< ès Rí:; jelentése a többitől fÖggetleniH hidrogén, szubszdtiíáSt hklrok&ítsi vagy bidrokarbií, R« jelentése hidrogén, hkirokarbit vagy szobsztituáii hMroktabii, X, jelentéseX? jeiéptése álkit, antinöalkii vagy alkattól, mindegyik 1:JS jelentése à iObbM! ISggeAëaM Iddsogiti, Mdroxi, aiidklip m}&>> tmmosIM, halogén, aikli, hsteroaril, Mfsav vagy aríi, z jelentése nem negativ szám is a 2b képletnél·; megfelelő amin legalább egy álí iicsopono· tartat tnaz, 54 A iS. igénypont szerimi gyógyászai:! késdtméity áXötí m«#atlrö^4 âfelmazâsra, ahoi m ás sje-issiésda febfelíő! Ikgpilentii p# is n jetatsse Ö vagy L 17. A 14 vagy 14 igéayimbi: szdmií |yég\ ásaad készítmény az ott megbafezog aikdmszásm, ago! |tm vágy 4** & Äbiiei ibggetléíiSÍ iégaláfeb ágy áll?}« vagy vsnllcsoporfot iaitafetszi vagy a 15, vagy 14, igény-potit sa&Ht# gyégÿiÈ fc$Âftéàÿ,; sítől (l)d pozitív egész szám as Rn- Maséa 4« egyfttessn legalább két áiiib vagy y5a:llasö|RaagttaSiíaimifa, vagy («} g.pzttlv egész szám és R.j, együttesen legalább két aillb vágy vinsiéSöpöftöt tartalmaz. ÍR. Az előző igéöypntok bármelyike szerinti gydgyá&zad készarneoy az olt meghatározást alkalmazásra, iäbol a lésálálősíítiátt asTsiagijtúsrér kloriöksssfoszfásgái köíésl méiaránya :t?°C*on 45-ös pH-ra podVréh, 26 mM blssCböt, 20 nsM Nkdí;>PO,:-ot is SÖ mM 2-fN-morfeilno)eiansKidfo»savm (MOS) tartalmazó, vizes, szimaláh vékonybél szervetlen pufterben legalább 0,5:1. 14 Az előző iginyposgítk háramlytke szerinti gyógyászati készítmény az btt migfcÄÖzott aikatmasÉaf* ahol a térbálbsított ssnlapolssoer AbsldlöatRisziátibá kötési mólaránya 3?X'-on fs$*ös pllAá pxsffereli, 3$ mM, XaO-ot, 20 mM NaH3jPöröí: 4s 50 miM z-CN'morÉsbítölátástSkdlföösavaí {MES) tiaí:aÍdíáZ4 vízé», sznimlált:: vékonybél szerveden pufferbe« („S1B”) legalább 1:1,
- 20, Ag előzd Igénypisstök bársnelyike szerlati gyógyászati Mszjttnésiy az ott meglnaÄzofi aüíahnazásra, aboi s íérbálOsitP: statinpoltmer kloridion: feszfáilun kötési mèiarâsya 3?®ß:<av 5,S'-ös pH^asoPfesvig 3b mM NáCi-ot, 2t) nM iXalWDi-ot és SO mM 2*(N^»0íföIöö)eteMfobsaváfc:(MES) tartalmazd,: vlze^ szimulált: vékonybél szefvetfeít pufidban („Síi· *) legalább 2:1, 21, Á0iloz6 igénypontok bármelyike szérlatl pOgyászad: kászitínény áz ott ínsgbatátzízod alkalmazásra, ahol á tédiálésitöií midtípölímet proíoökőtÖ ksgseiiása legalább 1Ö mmeté$ és kitjrldioakbtbi kapacitása légalább lOmmol/g 35 mM KaCl«öt és 63 tÄpCl«öt'»älme«6; «ta, szimulált gyomorRdyadéîc pallérban v„Sùr\ t ,2 -es pB -rt és 37^4-oo. 2¾. Az eiözb igénypontok bármelyike szerinti gyógyászati készitsnéiyi alkalmát«,, attól a sédiátcssfiott armnpoiimer egysosály* protontsotö r.apaciiása legalább I~t. mpioeg es kíOtxdioniíÖíÓ: kapâcv-ysa legalább 12 mmoO;ç. vagy egyessáijn protonkor kapacitása legalább 14 Tomôi%ésfcloridiooteb kaptéitib s.a iesnkíbb t4 rnnud/g IG mtnol/g 35 m.M HaCi’Qt as 4-· laKt HCooi tartalmast vizes» sz|n*pifΧft jgyppot&rlyu* dék palTefhBn (},SGF% l,z*es pH*0 é* '<·«*·
- 23. Azclbzô igénypontok bármelyike szerinti gyógyászai? készítmény as on meghátÉrOzott al.k»íhoa?ásta, &b<4 s« ktosidkbtés sí SIB assay-be» azután. bogy « polimert 37“0.on agy Art» & exponáltuk a lesztpmYemek, nagyobb mmî 2,0 mmot/g polimer. vagy nagyobb mim 2.5 mmol-'g pobmer. vágj nagyobb mim 3,0 romok g polimer, vagy nagyobb mint 3.5 mmoi/g polimer, vagy nagyobb műn a mmohg polimer 24 Az sk'V sgeoMvs KA V'mebdre '?"< ts ^rmvá*'«*, ter-bne·". .vr or megheímvíob ,3b dtme.m » áhöl kevesebb nom nap? I g. 0,5 g vagy 0,1 g nátriumot vagy káliumot adunk be. vsgy aboi nom adunk be nátriumot: vagy kâUuntm
- 25, Az ekb'.b igénypontok bármelyike szerinti gyégyásnati készítmény az ob meghatározóit tolod m&záom «női s ü,.pí \í,v eoto. \<\ "... 4 n -í '0g vagy ^ívn» V"í,í n "'s < ' \ '•eb'.ni t l‘l \< s. - km sebb mim 3 g, vsgy kevesebb mim 4 g, vagy kevesebb mint 3 g. 2b, Az eiôzô Igénypontok bármelyike: szertó'gyógyászati készítmény.«!» «pnieghatározott alkalmazásra, atei 3 napi dózis* naponta egyszer. kétszer vagy KárStezor adjak fes.
- 27. Az el&0: lS#3#pök btóseiysks bit imépatározoí-t: alkalmazásra,; ahol a íae-sboHkiiV aeidóm krónikus metabolite agltbzts,20, Áz eteö Ig4nypí>an)k bármelyike .»tutti gybgyászáb késkítmáhy az art megtósrözoíi: aikaimayásra, ahol a napi dózis 3 szérumban a bikarbónát tartósan > 1,6 rneq/i vagy >2 mexj/i vagy >3 meo-i vagy >$ me<j/l vagy >10 íneq/i emelkedéséi erítdményezi.
- 29. .Az. oíöxó igénypontok bánseiyike szerinti gyógyászati készítmény az ο» meghatározod alkalmazásra, ahol az eljárásban a dózist a kezelésre szoruló páciens szérum bikarbónái értéket vagy az addósos egveb indikátorai alapján tiiráljuk.
- 30. Azdózó igénypontok bármelyike szerinti gyógyászati készítmény1 áz ssit meghatározott aikáirnazátó, ahol a mslgbolikiís acidózis «spstl van jellemezve, hogy a sz#teb®b;;i%it^^^t értéke kisebb mint 22 mctpz
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