WO2002036098A1 - Method and preparation for binding acetaldehyde in saliva, stomach and large intestine - Google Patents
Method and preparation for binding acetaldehyde in saliva, stomach and large intestine Download PDFInfo
- Publication number
- WO2002036098A1 WO2002036098A1 PCT/FI2001/000948 FI0100948W WO0236098A1 WO 2002036098 A1 WO2002036098 A1 WO 2002036098A1 FI 0100948 W FI0100948 W FI 0100948W WO 0236098 A1 WO0236098 A1 WO 0236098A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acetaldehyde
- cysteine
- binding
- stomach
- pharmaceutical composition
- Prior art date
Links
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 title claims abstract description 288
- 210000002784 stomach Anatomy 0.000 title claims abstract description 68
- 210000002429 large intestine Anatomy 0.000 title claims abstract description 46
- 210000003296 saliva Anatomy 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims description 86
- 238000000034 method Methods 0.000 title claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 46
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 125000003277 amino group Chemical group 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 78
- 239000000126 substance Substances 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 60
- 229920000642 polymer Polymers 0.000 claims description 42
- 239000008187 granular material Substances 0.000 claims description 31
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 25
- 229960002433 cysteine Drugs 0.000 claims description 25
- 235000018417 cysteine Nutrition 0.000 claims description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 20
- -1 sulphhydryl Chemical group 0.000 claims description 20
- 235000013334 alcoholic beverage Nutrition 0.000 claims description 15
- 229940078469 dl- cysteine Drugs 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 10
- 229910001868 water Inorganic materials 0.000 claims description 10
- 229920001661 Chitosan Polymers 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 9
- 210000004369 blood Anatomy 0.000 claims description 9
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 9
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 9
- 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 9
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 claims description 8
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 8
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 8
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 210000003800 pharynx Anatomy 0.000 claims description 8
- 235000010413 sodium alginate Nutrition 0.000 claims description 8
- 239000000661 sodium alginate Substances 0.000 claims description 8
- 229940005550 sodium alginate Drugs 0.000 claims description 8
- 229920002125 Sokalan® Polymers 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 7
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- ZUKPVRWZDMRIEO-VKHMYHEASA-N L-cysteinylglycine Chemical compound SC[C@H]([NH3+])C(=O)NCC([O-])=O ZUKPVRWZDMRIEO-VKHMYHEASA-N 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- 230000007774 longterm Effects 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 150000008558 D-cysteines Chemical class 0.000 claims description 5
- 125000003158 alcohol group Chemical group 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 229940024606 amino acid Drugs 0.000 claims description 5
- 235000001014 amino acid Nutrition 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 4
- 150000008538 L-cysteines Chemical class 0.000 claims description 4
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 4
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 claims description 4
- 229960003121 arginine Drugs 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 229960005070 ascorbic acid Drugs 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 235000018102 proteins Nutrition 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- IAICFWDJMWEXAO-UHFFFAOYSA-N 2-(2-sulfanylethylamino)acetic acid Chemical compound OC(=O)CNCCS IAICFWDJMWEXAO-UHFFFAOYSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
- 102000009027 Albumins Human genes 0.000 claims description 3
- 108010088751 Albumins Proteins 0.000 claims description 3
- OELDIVRKHTYFNG-WDSKDSINSA-N Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CS OELDIVRKHTYFNG-WDSKDSINSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 3
- 108010016626 Dipeptides Proteins 0.000 claims description 3
- 229930195710 D‐cysteine Natural products 0.000 claims description 3
- 108010024636 Glutathione Proteins 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- FFFHZYDWPBMWHY-UHFFFAOYSA-N HOMOCYSTEINE Chemical compound OC(=O)C(N)CCS FFFHZYDWPBMWHY-UHFFFAOYSA-N 0.000 claims description 3
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 3
- 229920000148 Polycarbophil calcium Polymers 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 229960004308 acetylcysteine Drugs 0.000 claims description 3
- 235000009697 arginine Nutrition 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 108010016616 cysteinylglycine Proteins 0.000 claims description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 3
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 239000004296 sodium metabisulphite Substances 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000002734 metacrylic acid derivatives Chemical class 0.000 claims description 2
- 229960001639 penicillamine Drugs 0.000 claims description 2
- 230000004962 physiological condition Effects 0.000 claims description 2
- 125000001174 sulfone group Chemical group 0.000 claims description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 2
- 239000002211 L-ascorbic acid Substances 0.000 claims 2
- 235000000069 L-ascorbic acid Nutrition 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 102000004243 Tubulin Human genes 0.000 claims 1
- 108090000704 Tubulin Proteins 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 125000005395 methacrylic acid group Chemical group 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 230000008961 swelling Effects 0.000 claims 1
- 229960000344 thiamine hydrochloride Drugs 0.000 claims 1
- 235000019190 thiamine hydrochloride Nutrition 0.000 claims 1
- 239000011747 thiamine hydrochloride Substances 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical class SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 230000007423 decrease Effects 0.000 description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 210000000936 intestine Anatomy 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 8
- 210000004400 mucous membrane Anatomy 0.000 description 8
- 230000000391 smoking effect Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 7
- 239000002775 capsule Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000000711 cancerogenic effect Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 229920003137 Eudragit® S polymer Polymers 0.000 description 3
- 231100000315 carcinogenic Toxicity 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000007888 film coating Substances 0.000 description 3
- 238000009501 film coating Methods 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 229920001277 pectin Polymers 0.000 description 3
- 239000001814 pectin Substances 0.000 description 3
- 235000010987 pectin Nutrition 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000013405 beer Nutrition 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 239000007931 coated granule Substances 0.000 description 2
- 229930003935 flavonoid Chemical class 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000007269 microbial metabolism Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical group CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 229920003136 Eudragit® L polymer Polymers 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010019133 Hangover Diseases 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920003094 Methocel™ K4M Polymers 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Chemical class CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 208000025188 carcinoma of pharynx Diseases 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019987 cider Nutrition 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 235000020094 liqueur Nutrition 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000014594 pastries Nutrition 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000020046 sherry Nutrition 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Chemical class 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical class CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000019505 tobacco product Nutrition 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
Definitions
- the object of the invention is the use according to the preamble of claim 1 for preparing a pharmaceutical composition for locally binding the acetaldehyde in saliva, the stomach, and the large intestine.
- Another object of the invention is the pharma-ceutical compositions according to the preambles of claims 6, 11, and 19 and a method according to the preamble of claim 28 for decreasing the risk of developing cancer of the mouth, the pharynx, the oesophagus, the stomach, or the large intestine.
- acetaldehyde causes cancer in animals (Feron et al, (1982) Eur J Cancer Clin Oncol 18:13-31). It has also been found that acetaldehyde is a local carcinogen, when occurring in human saliva and the alimentary tract. This is supported by the fact that Asian heavy consumers of alcohol, who have a familial low-activity modification of aldehyde dehydrogenase-2 (ALDH2) enzyme, have both an increased risk of developing cancer of the mouth, the pharynx, and the alimentary tract, and an increased acetaldehyde content of the saliva after consuming alcohol (Vakevainen et al, (2000) Alcohol Clin Exp Res 24:873-877).
- ADH2 aldehyde dehydrogenase-2
- acetaldehyde is formed from alcohol as a consequence of hepatic metabolism and, according to recent research, locally in the alimentary tract through a microbial alcohol dehydrogenase (Salaspuro et al, (1996) Ann Med 28:195-200).
- Acetaldehyde also builds up in the stomach as a consequence of microbial metabolism in a situation, where there is no acid in the stomach or the acid has been removed by medication (Vakevainen et al, (2000) Alimentary Pharmacology Therapeutics, in press). It has also been shown that acetaldehyde builds up in the large intestine, because its bacteria that represent the normal flora are capable of converting ethanol into acetaldehyde (Jokelainen et al, (1996) Gut 39:100-104). The average amount of saliva excreted by a human is 1.5 litres a day. The areas of influence of the acetaldehyde contained by the saliva include the mouth, the pharynx, the oesophagus, and the stomach.
- Endogenous ethanol i.e., ethanol that builds up in the intestines in oxygen-free conditions as a consequence of microbes can also be found in the intestines.
- acetaldehyde is formed.
- Acetaldehyde is also formed in the mouth, the pharynx, and the upper airways as a consequence of smoking and exposure to air contamination. It has been proven that chronic smoking increases the acetaldehyde production of saliva originated in microbes.
- compositions containing the effective substances according to the present invention are known from before, the alleged effect of which is based on the reaction of the effective substances to the acetaldehyde inside blood and/or cells.
- the preparations in question are even capable of decreasing the acetaldehyde content of blood originating in alcohol.
- the known preparations also have such a composition that they would not be able to bind, on a long- term basis, the acetaldehyde, which is locally generated in the organism and which locally occurs in high contents (see publications US 5 202 354, US 4496 548, US 4 528 295, US 5 922 346).
- the acetaldehyde which forms in the organism during the consumption of alcohol and afterwards, also causes physiological symptoms called a hangover.
- an effort has been made to decrease the symptoms caused by acetaldehyde by taking preparations containing ascorbic acid, thiamine, cysteine or cysteic acid, and flavonoids or flavonoid complexes in a form of tablets swallowed orally in connection with, before or after consuming alcohol. It is believed that the method in question mostly decreases the acetaldehyde content in blood, because when swallowed, the effective substances go to the stomach and from there into the blood circulation.
- the tablets used in the method contained small amounts of effective substances only, and therefore had no effect on the acetaldehyde in saliva or the stomach (Matsuoka, US Pat No 5,202,354 and Moldowan et al, US Pat No 4,496,548).
- the object of the invention is to provide a method and a preparation for decreasing or removing the acetaldehyde content of the saliva, and consequently, that of the pharynx, the oesophagus, the stomach, and separately that of the large intestine and the stomach from the area of the mouth and the alimentary tract and from the upper airways.
- the use, the composition, and the method according to the invention are very useful in locally binding the increased acetaldehyde that occurs in connection with consuming alcoholic drinks or smoking.
- the acetaldehyde can originate from any source, such as a foodstuff containing acetaldehyde; the acetaldehyde can have been formed from the ethanol contained by the foodstuff or it can have been formed from an endogenous ethanol occurring in the organism.
- the purpose of the invention is to decrease the risk of contracting cancers of the mouth and the alimentary tract, which are caused by the acetaldehyde in the said areas.
- the invention is based on the surprising observation that the harmful amount of acetaldehyde locally occurring in saliva, the stomach or the large intestine can be bound locally, quickly and in large concentrations into a chemically safe form by using the preparations according to the present invention.
- compounds that comprise one or more free sulphhydryl and/or amino groups are used to prepare a pharmaceutical compound, which is used to locally bind the acetaldehyde in saliva, the stomach or the large intestine.
- compositions according to the characterizing part of claim 6 for binding acetaldehyde from saliva a pharmaceutical composition according to the characterizing part of claim 11 for binding acetaldehyde from the stomach, and a pharmaceutical composition according to the characterizing part of claim 19 for binding acetaldehyde from the large intestine.
- the pharmaceutical composition comprises one or more substances that bind acetaldehyde, as bound to a pharmaceutically acceptable carrier.
- the substances contained by the composition are selected so that the substances that are capable of binding acetaldehyde are released within a long period of time.
- Another object of the invention is a method according to the characterizing part of claim 28 for decreasing the effect of acetaldehyde, which causes cancer, in human saliva, the stomach or the large intestine.
- the acetaldehyde contained by saliva, the stomach or the large intestine is locally bound into a safe form by using a pharmaceutical composition that releases one or more acetaldehyde-binding substances.
- the pharmaceutical compositions comprising acetaldehyde-binding compounds can be used to decrease the risk of developing cancer of the mouth, the pharynx, the oesophagus, the stomach, and the large intestine.
- the compositions according to the invention can be used for large- scale consumers of alcohol and especially for those, who have a familial low-activity modification of the aldehyde dehydrogenase-2 (ALDH2) enzyme.
- ALDH2 aldehyde dehydrogenase-2
- the use of the compositions according to the invention is also of benefit to those who consume moderate amounts of alcohol or who consume foodstuffs that contain small contents of alcohol or acetaldehyde.
- the use of the compositions according to the invention also benefits smokers.
- the appended drawing shows the measuring results of the acetaldehyde contents of the saliva of the test groups as the function of time, according to Example 1.
- Fig. 1 shows the acetaldehyde content as the function of time in the saliva of the persons in a control group and that of the participants in the test group who used the acetaldehyde- binding preparation according to the invention.
- Fig. 2 shows the acetaldehyde content ( ⁇ mol 1) of the contents of a human bowel as the function of time in a control sample and in three samples, to which a preparation containing 100, 300, and 500 mg of an acetaldehyde-binding substance was added.
- the acetaldehyde-bmding substance refers to a compound comprising one or more free sulphhydryl, amino or hydroxyl groups.
- Cysteine and its derivatives are especially well suited to the purpose according to the invention.
- the most suitable amino acids for the use according to the invention are L and D-cysteines.
- the binding of acetaldehyde refers to a chemical reaction between the acetaldehyde and the compound that has a free sulphhydryl and or amino group, wherein the acetaldehyde jointly with the "acetaldehyde-binding substance" forms a larger molecule, and water can be formed in the reaction.
- the acetaldehyde when reacting with cysteine, the acetaldehyde binds itself both to the sulphhydryl and the amino group and forms 2- methyl-L-thiazolidine-4-carboxylic acid and water.
- the acetaldehyde can bind itself to the amino group of almost any protein, whereby Schiff s base or a 2-methyl-imidazole ring is formed.
- the compounds obtained from acetaldehyde by chemically bmding are safe for the organism.
- Suitable compounds for binding acetaldehyde in the organism also include the compounds according to the formula (I):
- R 1 is hydrogen or an acyl group with 1-4 carbon atoms
- R 2 is a sulphhydryl or sulphone group, n is 1 or 2.
- R is derived from a protein (e.g., haemoglobin, albumin or tubuline)
- R is derived from a protein (e.g., haemoglobin, albumin or tubuline).
- Amino acids or other compounds that suitably bind acetaldehyde and comprise a free sulphhydryl (SH) and or amino (NH 2 ) group include: L-cysteine,
- acetaldehyde-binding compounds that cause no health hazard in the amounts according to the invention are suitable for the preparations according to the present invention.
- the long-term binding of acetaldehyde means keeping the acetaldehyde content for at least 30 minutes, preferably over 60 minutes, and most preferably over 120 minutes below a limit that is considered harmful, or preferably on a lower level than in a case where no pharmaceutical composition is used.
- a harmful/carcinogenic content of acetaldehyde in the human mouth, oesophagus, stomach, and large intestine is 20-800 ⁇ mol/1 of saliva or the contents of the intestine.
- acetaldehyde content essentially lower than without the use of the pharmaceutical composition means keeping the acetaldehyde content at a level that is at least 20%, preferably over 40%, and most preferably over 60% lower than when not using the pharmaceutical composition.
- Such a harmful or carcinogenic content of acetaldehyde in the human mouth, oesophagus, stomach or large intestine can be obtained in connection with consuming alcoholic drinks, particularly strong alcoholic drinks, or foodstuffs containing alcohol, as a consequence of smoking or when consuming preparations containing acetaldehyde.
- Alcohol drinks are ethanol-containing drinks, the ethanol content varying within 0.7% by volume and 84% by volume.”
- Alcohol foodstuffs refer to foodstuffs containing at least 0.7% of ethanol. Such foodstuffs can be, for example, fermented juices or preserves, or foodstuffs preserved with small amounts of alcohol, pastries, jellies, and mousse seasoned with liqueur or corresponding preparations containing alcohol.
- the use of the preparations according to the invention can be of benefit even, when light alcoholic drinks or foodstuffs are consumed, which contain small amounts of alcohol. Some foodstuffs can also already contain acetaldehyde. Acetaldehyde-containing foodstuffs, which have ethanol that is generated in connection with fermentation, such as beer, cider, wine, home-brewed beer, and other alcoholic drinks, as well as many juices. As for alcoholic drinks, sherry contains an especially large amount of acetaldehyde. "In connection with consuming alcohol” herein refers to the period of time that begins from starting to enjoy alcohol and ends, when there is no more alcohol in the blood.
- a local, long-acting preparation that is placed in the mouth refers to all preparations that are placed between the cheek or the lip and the gum, or preparations that are sucked or chewed in the mouth, and in which the release of the substance intended to have a local effect in the mouth, the pharynx, the oesophagus or the stomach is prolonged.
- a prolonged release of the effective substance means that the release of the substance takes 30 minutes at the minimum, preferably 120 minutes at the minimum, most preferably over four hours. By using the compositions according to the invention, release times of the effective substance of as much as 4-8 hours can be achieved.
- the compounds that are used in the preparation that binds acetaldehyde can be compounds comprising one or more free sulphhydryl and/or amino groups.
- At least one substance that regulates the release rate of the effective substance is added to the locally long-acting pharmaceutical composition, which is placed in the mouth and can be in the form of a tablet. It is preferably that the composition also ensures that the preparation adheres to the mucous membrane of the mouth.
- both the release rate of the effective substance can advantageously be regulated and the adherence of the preparation to the mucous membrane of the mouth can be ensured.
- the release rate of the effective substance and the adhesion of the preparation to the mucous membrane can be regulated.
- the total amount of polymers in the preparation is 10-50%, preferably 15-40%, and most preferably 20-30%.
- a dosage unit of the pharmaceutical composition can comprise 50-500 mg of acetaldehyde-binding substance; preferably the amount of acetaldehyde-binding substance is 50-300 mg, and most preferably 100-200 mg.
- the preparations according to the invention can be placed in the mouth 1 or 2 at a time and they can be replaced by new ones at 4 to 10-hour intervals, preferably at 6 to 8-hour intervals.
- composition of the long-acting tablet that is placed in the mouth can be as follows, for example:
- Non-ionised macromolecules include, for example, methylcellulose (MC), hydroxypropylcellulose (HPC), and hydroxypropyl-methylcellulose (HPMC), and polyethylene glycol (PEG).
- Ionising polymers include, for example, sodium carboxy- methyl cellulose (NaCMC), alginic acid, sodium alginate, chitosan, polycarbophil (NoveonTM), and cabomer (CarbopolTM).
- a long-acting preparation that has a local effect on the stomach refers to all monolithic or multiparticular tablets or capsules or granules as such, which, when wetted under the influence of the gastric juices adhere to the mucous membrane of the stomach or form a gel that floats in the contents of the stomach, as a consequence of which their residence time in the stomach is prolonged and thus enables a prolonged release in and a local effect of the drug on the stomach.
- the long-acting preparation that locally acts on the stomach can be a liquid preparation taken orally (mixture), the physical structure of which is a gel.
- a special property required of the pharmaceutical composition that has a local effect on the stomach is that it remains in the stomach for as long as possible.
- this can be solved in two ways: by making a preparation that adheres to the mucous membrane of the stomach or making a preparation that floats in the contents of the stomach.
- the preparation can be rendered fixable to the mucous membrane of the stomach by using as additives cationic polymers, such as various chitosan grades.
- Preparations that float in the stomach are provided by using polymers (e.g., alginic acid) that form a gel and by adding to the preparation sodium hydrogen carbonate, which under the influence of gastric acid releases carbon dioxide, which in turn forms gas bubbles inside the gel.
- a liquid gel that floats in the stomach can also be prepared from sodium alginate, aluminium hydroxide, sodium hydrogen carbonate, and water, to which the acetaldehyde-binding compound can be added.
- a corresponding liquid preparation is also obtained by adding an acetaldehyde- binding substance to an aqueous dispersion of chitosan.
- Another preparation that remains in the stomach for a long time is a preparation, which is known as HBSTM (hydrodynamically balanced system).
- the preparation can remain in the stomach for a long time, when a relatively large tablet is made of it (with a diameter of at least 7-10 mm) and it is coated with a film, which does not decompose in the alimentary tract, and which, however, releases an effective substance (OrosTM) through a hole which has been made to it, for example.
- an effective substance OrosTM
- a prerequisite is that such a preparation be consumed after eating.
- a single dose of the pharmaceutical composition having a local effect on the stomach comprises 50-500 mg of acetaldehyde-binding substance; preferably the amount of acetaldehyde-binding substance is 50-300 mg, and most preferably 100-200 mg.
- the dosage When needed, the dosage is renewed at 4 to 10-hour intervals, preferably at 6 to 8-hour intervals.
- the amount of compound released in the conditions of the stomach is preferably 40-80 mg in an hour.
- the preparation according to the invention which releases in the stomach, has at least one - often two - polymers, which have the task of keeping the drug as long as possible, for two hours minimum, in the stomach either so that it attaches the preparation to the mucous membrane of the stomach or forms a gel that floats in the contents of the stomach. Another task of the polymers is to prolong the release of the effective substance.
- the preparation that locally binds acetaldehyde in the stomach can be a tablet that forms a gel in the stomach or a capsule comprising a mixture of powder or granules that forms a gel.
- the preparation comprises polymers that form a gel in the stomach, such as chitosans, a ⁇ ginates, sodium carboxy-methylcellulose grades, carbomers or aluminium hydroxide.
- the preparation can also comprise sodium hydrogen carbonate.
- the amount of polymers in the preparation is 10-50%, preferably 15-40%, and most preferably 20- 30%.
- the amount of sodium hydrogen carbonate can be 10-30%, preferably 20% of the amount of polymers.
- the preparation that locally binds acetaldehyde in the stomach can be a tablet or granule preparation, wherein the acetaldehyde-binding substance is mixed with the fillers needed and, after that, granulated by using enteric polymers as binders.
- the binder used can be any known enteric polymer, preferably a polymer with a solution pH of 6-7, and most preferably the polymer is any of the methacrylate derivatives, which are known by the trade names Eudragit L and Eudragit S.
- the amount of enteric polymer in the preparation is preferably 2-5%, most preferably 3-4%.
- the preparation that locally binds acetaldehyde in the stomach can be a liquid preparation, i.e., a mixture comprising, in addition to the acetaldehyde-binding substance, also sodium alginate, aluminium hydroxide, sodium hydrogen carbonate, and water.
- the amount of water in the whole preparation is 70-90%, most preferably about 75-85%.
- the amount of sodium alginate in the preparation is preferably 2-10%, most preferably about 5%, and the amount of aluminium hydroxide is preferably 5-15%, most preferably about 10%.
- composition of the preparation comprising granules can be as follows, for example:
- the relative composition of the liquid preparation can be as follows, for example:
- a long-acting preparation that has a local effect in the large intestine refers to all monolithic or multiparticular tablets or capsules or granules as such, which will not release the dose in a prolonged way until the preparation has drifted to the end of the small intestine or all the way to the large intestine.
- the preparation according to the invention that releases acetaldehyde-bmding substances in the large intestine in a prolonged way, carries the acetaldehyde-binding substance to the last part of the small intestine or to the large intestine before the substance in question is allowed to be released - whichever the releasing mechanism.
- the pharmaceutical composition that binds acetaldehyde in the large intestine is administered orally.
- the most functional solutions are based on the use of enteric polymers.
- a film coating which does not dissolve in the acidic environment of the stomach, but dissolves at a pH value of 7 at the latest, can be made both on the tablet and the granules.
- polysaccharides that degrade under the effect of microbes of the large intestine, or polymers generated by azo bonds.
- OrosTM can also be used, when its opening is first covered with an enteric polymer, the solution pH of which is ⁇ 7.
- Useful enteric polymers include, for example, the grades of hydroxypropyl methylcellulose- acetatesuccinate (HPMC-AS) sold by the trade name AqoatTM, Aqoat AS-HFTM in particular, a cellulose acetatephtalate (CAP) grade sold by the trade name AquatericTM, and methacrylic acid- methylmethacrylate copolymers, the grade sold by the trade name Eudragit-STM in particular.
- HPMC-AS hydroxypropyl methylcellulose- acetatesuccinate
- Aqoat AS-HFTM in particular
- CAP cellulose acetatephtalate
- AquatericTM methacrylic acid- methylmethacrylate copolymers
- the preparation according to the invention has at least one ingredient, which adjusts the release of the effective substance not to take place until at the end of the small intestine or in the large intestine.
- the polymer that controls the place of release can form a film around the entire preparation. It can also form a film around the particles (granules) contained by the multiple-part preparation.
- the polymer that degrades under the effect of the enzymes secreted by the bacteria of the large intestine can also be as a filler in a monolithic preparation, or as a filler in the granules or in a multiple-unit preparation prepared from these granules.
- the preparation according to the invention is an enteric tablet, the film coating of which does not dissolve until at the end of the small intestine or at the beginning of the large intestine.
- the dissolution pH of the polymer that forms the film is 6.0-7.5, preferably 6.5- 7.0.
- the amount of enteric polymer that forms the film is 5-20%, preferably 10-15% of the whole mass of the tablet.
- the filler of the tablet can comprise pharmaceutical additives that do not swell, such as calcium hydrogen phosphate.
- the preparation according to the invention can also be granules that comprise an acetaldehyde-binding substance and are coated with an enteric film, the dissolution pH of the film-forming polymer being 6.0-7.5, preferably 6.5-7.0.
- the amount of film-forming enteric polymer of the entire mass of the granule is 5-30%, preferably 15-25%.
- the granule can comprise 20-40%, preferably about 30% of filler poorly soluble in water, such as calcium hydrogen phosphate.
- the binder of the granule coated with the enteric film can be an enteric polymer, the dissolution pH of which is 6.0-7.5, preferably 6.5-7.0.
- the amount of binder in the granule is 2-5%, preferably 3-4%.
- the preparation according to the invention can also be a tablet comprising the enteric coated granules described above, on which an enteric film has also been made.
- the tablet made for such a preparation not only comprises enteric granules, but also a filler suitable for direct compression, such as microcrystalline cellulose, the amount of which in the tablet is 30-70%, preferably 40-60%.
- the dosage unit of the pharmaceutical composition preferably comprises 50-500 mg of acetaldehyde-binding substance; preferably the amount of acetaldehyde-binding substance is 50- 300 mg, and most preferably 100-200 mg.
- the amount of compound releasing in the conditions of the large intestine is preferably 50-100 mg in an hour.
- the dosage can be repeated at 4 to 10-hour intervals, preferably at 6 to 8- hour intervals.
- composition of the enteric tablet which comprises enteric granules and binds acetaldehyde in the desired way, can be as follows, for example:
- Enteric granules Acetaldehyde-binding substance 100 mg
- Filler e.g., calcium hydrogen phosphate 30 - 50 mg
- Enteric tablet Enteric granules 170 - 210 mg
- Lubricants e.g. magnesium stearate and talcum 5 - 10 mg
- the content of acetaldehyde formed in saliva as a consequence of consuming alcoholic drinks, smoking or for some other reason can be decreased so that, for example, in connection with consuming alcoholic drinks or smoking, a preparation is placed in the mouth, under the upper lip, for example, which at a suitable rate releases cysteine or a similar acetaldehyde binding agents.
- the acetaldehyde content of saliva decreases by over 20%, preferably by over 40%, most preferably over 60%, typically by 60-80% compared with a placebo.
- 100 mg of cysteine in the preparation is enough to have the desired effect for 4-5 hours.
- a new preparation is placed in the mouth after the previous one has dissolved. This is repeated as long as there is alcohol in the blood.
- the acetaldehyde content locally increased in the stomach as a consequence of consuming alcoholic drinks can be decreased by more than 20%, preferably over 40%, most preferably over 60%, typically 60-80% compared with a placebo by consuming, in connection with alcoholic drinks, a pharmaceutical composition that releases an acetaldehyde-binding compound at a suitable rate in the stomach.
- the preparations that bind acetaldehyde and affect the mouth, the stomach, and the large intestine can also be used simultaneously.
- the acetaldehyde content formed from consumed or endogenous ethanol in the large intestine can be decreased by over 20%, preferably over 40%, most preferably 60-80% compared with a placebo by consuming a preparation, which in the large intestine releases acetaldehyde-binding compounds at a suitable rate.
- cysteine in the preparation was 100 mg.
- the participants consumed 0.8 g/kg of ethanol in the form of a drink containing 10 % by volume of ethanol.
- the acetaldehyde contents of the saliva of the testees were measured at 20-minute intervals. The acetaldehyde contents of the saliva of the participants who used the cysteine-containing preparation was 3-5 times lower than that of the participants in the reference group during the entire measuring period.
- Fig. 1 shows the acetaldehyde content (Ach ⁇ mol/1) measured for the saliva of the control group testees (•) and the group, who used the preparation according to the invention (o), as a function of time (min).
- the pharmaceutical composition placed in the mouth which has a long-term local effect, can be prepared and used to decrease the risk of cancer caused by acetaldehyde as follows:
- composition of a capsule placed in the mouth can be as follows, for example: Cysteine 100.0 mg HPMC (Methocel K4MTM) 30.0 mg
- Carbomer (Carbopol 971P NFTM 6.9 mg
- Cysteine, HPMC, and carbomer are mixed carefully by using mixers generally used in the pharmaceutical industry.
- magnesium stearate is also added to the mixture to function as lubricant of the mould of the tablet-compressing machine.
- Tablets (with a diameter of 9 mm) are compressed from the powder mixture by using conventional tablet machines. The preparation is placed in the mouth in connection with consuming alcohol. As long as there is alcohol in the blood, a new capsule is taken after the previous one has dissolved.
- the locally long-acting pharmaceutical preparation that binds acetaldehyde in the stomach can be prepared and used to decrease the risk of cancer caused by acetaldehyde as follows:
- the relative composition of the preparation that locally binds acetaldehyde in the stomach can be as follows, for example:
- the powder mixture is mixed by conventional mixers (such as a blender), which are used in the drug industry. After that, the powder rnixture is granulated using a 2.5% acetic acid as a granulation liquid.
- the granulation liquid can be added to the same blender.
- the moist powder mass is compresses through a screen plate or a perforated plate (the diameter of the aperture being 2 mm).
- the formed granules are dried and screened. A screen fraction of 1.2-1.7 mm is recovered, which is dispensed into hard gelatine capsules so that the dose of cysteine is 100 mg.
- the tablets prepared above are ingested to decrease the risk of cancer locally caused by acetaldehyde in occasions, which are favourable for an increase in the acetaldehyde content of the stomach, such as in connection with consuming alcoholic drinks.
- the dosage is given at 4 to 6-hour intervals as long as there is alcohol in the blood.
- the pharmaceutical composition that releases acetaldehyde-binding substances in the large intestine in a prolonged way can be prepared and used to decrease the risk of cancer caused by acetaldehyde as follows.
- composition of the enteric tablet which comprises enteric granules and binds acetaldehyde in the desired way, can be as follows, for example:
- Enteric tablet Enteric granules 185 mg
- Cysteine and the calcium hydrogen phosphate that works as a filling agent are mixed together.
- Eudragit S is dissolved in ethanol (a 20% solution) and the solution is used to moisten the powder mixture. The wet mass is compressed into granules. The dried granules are screened and a granule fraction of 1.2-1.7 mm is coated with Aqoat AS-HF.
- the composition of the coating solution is as follows: Aqoat AS-HF 10%, triethylcitrate 3.5%, magnesium strearate 3%, and water 83.5%.
- the coated granules are mixed with microcrystalline cellulose (e.g., Emcocel LP 200TM) and, finally, the lubricants are added to the mixture: magnesium stearate and talcum.
- the mixture is compressed into tablets and, finally; an enteric film is made on the tablet in the same way as on the granules.
- mixers, granulators, screening equipment, film coating equipment, and tablet compressing machines which are generally used in the pharmaceutical industry, can be used.
- the composition prepared above is ingested orally in connection with consuming alcoholic drinks and the dosage is repeated at 4 to 6-hour intervals as long as there is alcohol in the blood.
- acetaldehyde was inactivated in vitro in the contents of the intestine by using the tablet according to the invention, which slowly released cysteine.
- the preparation was a compression- coated tablet, the coating material thereof being a polysaccharide, pectin, which degrades under the influence of microbes of the large intestine.
- the composition of the preparation used in the trial was as follows:
- 1 st sample control without cysteine (contained additives of tablets, e.g., pectin)
- 2nd sample 100 mg of cysteine (i.e., one tablet)
- 3rd sample 300 mg of cysteine (i.e., 3 tablets)
- 4th sample 500 mg of cysteine (i.e., 5 tablets)
- the samples were incubated (i.e., the conditions in question were maintained to cause a reaction) at a temperature of 37°C in a water bath (corresponding to the temperature of the human body), slightly mixing all the time.
- 500- ⁇ l samples were taken from the excrement samples at about 1-hour intervals to analyse the concentrations of acetaldehyde and ethanol by gas chromatography. These samples were taken during a period of 600 minutes in total.
- Fig. 2 shows the acetaldehyde content of the intestine ( ⁇ mol/1) as the function of time in a control sample, to which no preparation according to the invention had been added, and in three samples, to which preparations containing 100, 300, and 500 mg of effective substance had been added.
- a 100-mg cysteine tablet decreased the amount of acetaldehyde in the samples by 51% compared with the control sample and, 300-mg and 500-mg tablets by 68% and 66%, correspondingly.
- the response of the acetaldehyde content of the samples is a good indication of how the preparation according to the invention considerably decreases the acetaldehyde content generated from ethanol under the effect of microbes in the contents of the intestine.
- the conditions corresponded well to in vivo conditions.
- the effective substance which contains a very reactive SH group, reacts in the intestinal juice exactly as desired, i.e., the effective substance, for example, is not uselessly consumed in reactions with the other compounds of the contents of the intestine.
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Confectionery (AREA)
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002212395A AU2002212395A1 (en) | 2000-10-30 | 2001-10-30 | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
EP01980581A EP1339394B1 (en) | 2000-10-30 | 2001-10-30 | Pharmaceutical preparation for binding acetaldehyde in saliva, stomach and large intestine |
EA200300532A EA009335B1 (en) | 2000-10-30 | 2001-10-30 | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
US10/415,422 US9474733B2 (en) | 2000-10-30 | 2001-10-30 | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
JP2002538910A JP4691312B2 (en) | 2000-10-30 | 2001-10-30 | Methods and formulations for binding acetaldehyde in saliva, stomach and large intestine |
AT01980581T ATE522203T1 (en) | 2000-10-30 | 2001-10-30 | PHARMACEUTICAL PRODUCTION FOR BINDING ACETALDEHYDE IN SALIVA, STOMACH AND LARGE INTESTINE |
US11/783,333 US20080000489A1 (en) | 2000-10-30 | 2007-04-09 | Method and preparation for binding aldehydes in saliva |
US13/004,302 US20110171296A1 (en) | 2000-10-30 | 2011-01-11 | Method and preparation for binding acetaldehyde in saliva, the stomach and the large intestine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20002392A FI121528B (en) | 2000-10-30 | 2000-10-30 | Pharmaceutical composition to reduce the risk of sunk in cancer by binding acetaldehyde in saliva, stomach and colon |
FI20002392 | 2000-10-30 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/783,333 Continuation-In-Part US20080000489A1 (en) | 2000-10-30 | 2007-04-09 | Method and preparation for binding aldehydes in saliva |
US13/004,302 Continuation-In-Part US20110171296A1 (en) | 2000-10-30 | 2011-01-11 | Method and preparation for binding acetaldehyde in saliva, the stomach and the large intestine |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002036098A1 true WO2002036098A1 (en) | 2002-05-10 |
Family
ID=8559405
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FI2001/000948 WO2002036098A1 (en) | 2000-10-30 | 2001-10-30 | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
Country Status (10)
Country | Link |
---|---|
US (1) | US9474733B2 (en) |
EP (1) | EP1339394B1 (en) |
JP (1) | JP4691312B2 (en) |
CN (1) | CN100467016C (en) |
AT (1) | ATE522203T1 (en) |
AU (1) | AU2002212395A1 (en) |
EA (1) | EA009335B1 (en) |
ES (1) | ES2370811T3 (en) |
FI (1) | FI121528B (en) |
WO (1) | WO2002036098A1 (en) |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6685917B2 (en) | 2000-11-22 | 2004-02-03 | Rxkinetix, Inc. | Treatment of mucositis |
WO2006037848A1 (en) * | 2004-10-08 | 2006-04-13 | Biohit Oyj | Method and preparation for binding aldehydes in saliva |
WO2006103316A1 (en) * | 2005-04-01 | 2006-10-05 | Biohit Oyj | Food composition for binding acetaldehyde in mouth and in digestive track, and method for the preparation of the composition |
WO2007009012A2 (en) * | 2005-07-13 | 2007-01-18 | Al Czap | Compositions for oral administration of sustained release glutathione, methods for their production and uses thereof |
WO2007135241A2 (en) * | 2006-05-22 | 2007-11-29 | Biohit Oyj | Composition and method for binding acetaldehyde in stomach |
US7501452B2 (en) | 2005-11-30 | 2009-03-10 | Endo Pharmaceuticals Inc. | Treatment of xerostomia |
WO2009034232A1 (en) | 2007-09-14 | 2009-03-19 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
WO2009087615A1 (en) * | 2008-01-09 | 2009-07-16 | Amino Acid Solutions Inc. | Pharmaceutical compositions and methods utilizing a d-amino acid and an antioxidant for treating neuropsychiatric disorders |
WO2013001167A1 (en) * | 2011-06-29 | 2013-01-03 | Biohit Oyj | Non-toxic compositions for decreasing the risk of cancer caused by oral microbes |
WO2013178880A1 (en) | 2012-05-28 | 2013-12-05 | Biohit Oyj | Composition for preventing headaches |
WO2014140411A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Encapsulated composition for binding aldehydes in the stomach |
WO2014140410A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Composition for oral administration for binding aldehydes in the gastrointestinal tract |
WO2015132472A1 (en) | 2014-03-06 | 2015-09-11 | Biohit Oyj | Composition for binding aldehydes and free radicals in the gastrointestinal tract |
US9474733B2 (en) | 2000-10-30 | 2016-10-25 | Biohit Oyj | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
EP2950794A4 (en) * | 2013-02-01 | 2016-11-09 | Biohit Oyj | Composition for binding aldehydes in the mouth |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITME20040015A1 (en) * | 2004-12-07 | 2005-03-07 | Vincenzo Savica | CHEWING GUM, RUBBER CANDIES, TABLETS, SLOW TABLETS OF CHELANTI PHOSPHATE AND / OR PHOSPHORUS SALIVAR AND CAPSULES WITH SLOW RELEASE OF CHELANTS PHOSPHATE AND / OR PHOSPHORUS AT GASTROENTERIC LEVEL. |
US20100166833A1 (en) * | 2007-05-07 | 2010-07-01 | Technion Research & Development Foundation Ltd. | Compositions, articles and methods for preventing or reducing tobacco-associated damage |
FI120526B (en) * | 2007-05-16 | 2009-11-30 | Biohit Oyj | Filter for tobacco product |
US20090092664A1 (en) * | 2007-10-08 | 2009-04-09 | University Of Kentucky Research Foundation | Polymer-metal chelator conjugates and uses thereof |
CN108671232A (en) * | 2018-07-09 | 2018-10-19 | 珠海中科先进技术研究院有限公司 | A kind of combination preparation that can reduce internal acetaldehyde concentration and preparation method thereof and purposes |
US11717554B2 (en) * | 2019-09-19 | 2023-08-08 | Max R&D Llc | Method for preventing or treating hangover symptom(s) associated with consumption of alcoholic beverage(s) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4528295A (en) * | 1983-08-15 | 1985-07-09 | Boris Tabakoff | Composition and method for reducing blood acetaldehyde levels |
EP0234464A1 (en) * | 1986-02-18 | 1987-09-02 | Takeda Chemical Industries, Ltd. | Composition and method for reducing acetaldehyde toxicity |
JPH0374327A (en) * | 1989-08-16 | 1991-03-28 | Ajinomoto Co Inc | Excitometabolic agent for alcohol |
JPH06116144A (en) * | 1992-10-07 | 1994-04-26 | Shuichi Kimura | Composition for preventing alcoholic hepatopathy |
US5922346A (en) * | 1997-12-01 | 1999-07-13 | Thione International, Inc. | Antioxidant preparation |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0054795B1 (en) * | 1980-12-09 | 1987-07-15 | Teijin Limited | Novel halogenated prostacyclins, process for the production thereof, and pharmaceutical use thereof |
US4496548A (en) | 1983-02-04 | 1985-01-29 | Moldowan Mervin J | Composition and method for reducing hangover |
GB8313044D0 (en) | 1983-05-12 | 1983-06-15 | Caseley J R | Reducing toxic effects of tobacco |
JPS6116144A (en) | 1984-06-29 | 1986-01-24 | Fujitsu Ten Ltd | Abnormal gear shift warning device |
US5202354A (en) * | 1986-02-18 | 1993-04-13 | Takeda Chemical Industries, Ltd. | Composition and method for reducing acetaldehyde toxicity |
JPS62195323A (en) * | 1986-02-24 | 1987-08-28 | Eisai Co Ltd | Gastric resident particle |
GB2201594B (en) * | 1986-06-24 | 1991-02-13 | Istvan Racz | Production of acid binding pharmaceutical preparations |
ES2038669T3 (en) * | 1986-09-18 | 1993-08-01 | London School Of Pharmacy Innovations Ltd | PHARMACEUTICAL FORMULATION. |
HU201865B (en) | 1989-04-28 | 1991-01-28 | Pecsi Dohanygyar | Tobacco-smoke filter of high efficiency |
JPH03136895A (en) | 1989-10-23 | 1991-06-11 | Fuji Electric Co Ltd | Manufacture of optical data recording medium |
JPH0421635A (en) | 1990-05-16 | 1992-01-24 | Suntory Ltd | Toxicity-suppressing agent of acetaldehyde and drink and food effective in suppression of toxicity of acetaldehyde |
US5110423A (en) * | 1990-05-25 | 1992-05-05 | Technic Inc. | Bath for electroplating bright tin or tin-lead alloys and method thereof |
JP3013860B2 (en) | 1991-03-22 | 2000-02-28 | 三菱瓦斯化学株式会社 | Food preservative and method for preserving food using the same |
FI93924C (en) * | 1991-09-17 | 1995-06-26 | Martti Lauri Antero Marvola | A method of preparing a controlled release formulation |
US5169638A (en) * | 1991-10-23 | 1992-12-08 | E. R. Squibb & Sons, Inc. | Buoyant controlled release powder formulation |
US5958458A (en) * | 1994-06-15 | 1999-09-28 | Dumex-Alpharma A/S | Pharmaceutical multiple unit particulate formulation in the form of coated cores |
US5695781A (en) * | 1995-03-01 | 1997-12-09 | Hallmark Pharmaceuticals, Inc. | Sustained release formulation containing three different types of polymers |
JPH09194361A (en) * | 1996-01-19 | 1997-07-29 | Wakunaga Pharmaceut Co Ltd | Antitumor agent |
WO1998003260A1 (en) * | 1996-07-22 | 1998-01-29 | Kouki Bussan Yugenkaisha | Novel adsorbent |
IN186245B (en) * | 1997-09-19 | 2001-07-14 | Ranbaxy Lab Ltd | |
US5829449A (en) | 1997-09-19 | 1998-11-03 | Thione International, Inc. | Smoking products containing antioxidants |
AU4398299A (en) | 1999-05-24 | 2000-12-12 | Hee Jung Kim | Composition for recovering from a hangover and for preventing brain cell damage |
EP1244455B1 (en) * | 1999-10-29 | 2009-07-22 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
FI121528B (en) | 2000-10-30 | 2010-12-31 | Biohit Oyj | Pharmaceutical composition to reduce the risk of sunk in cancer by binding acetaldehyde in saliva, stomach and colon |
ITPI20010014A1 (en) | 2001-03-05 | 2002-09-05 | Ivo Pera | COMPOUND FOR FILTERS FOR CIGARETTES, OR OTHER SMOKING ITEMS, BASED ON ANTIOXIDANT SUBSTANCES AND THE FILTER SO OBTAINED |
WO2002098405A1 (en) | 2001-06-05 | 2002-12-12 | Ajinomoto Co., Inc. | Liver fibrosis inhibitors |
JP2003055215A (en) | 2001-06-05 | 2003-02-26 | Ajinomoto Co Inc | Hepatic fibrosis inhibitor |
US6936283B2 (en) * | 2003-07-25 | 2005-08-30 | Langeland Bjoern T. | Composition for stimulation of specific metallo-enzymes |
US20070218106A1 (en) | 2004-02-17 | 2007-09-20 | Matuschka-Greiffenclau Markus | Alcohol Metabolism Moderating Composition |
-
2000
- 2000-10-30 FI FI20002392A patent/FI121528B/en not_active IP Right Cessation
-
2001
- 2001-10-30 US US10/415,422 patent/US9474733B2/en active Active
- 2001-10-30 CN CNB018216285A patent/CN100467016C/en not_active Expired - Lifetime
- 2001-10-30 JP JP2002538910A patent/JP4691312B2/en not_active Expired - Lifetime
- 2001-10-30 WO PCT/FI2001/000948 patent/WO2002036098A1/en active Application Filing
- 2001-10-30 AU AU2002212395A patent/AU2002212395A1/en not_active Abandoned
- 2001-10-30 AT AT01980581T patent/ATE522203T1/en not_active IP Right Cessation
- 2001-10-30 ES ES01980581T patent/ES2370811T3/en not_active Expired - Lifetime
- 2001-10-30 EA EA200300532A patent/EA009335B1/en not_active IP Right Cessation
- 2001-10-30 EP EP01980581A patent/EP1339394B1/en not_active Expired - Lifetime
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4528295A (en) * | 1983-08-15 | 1985-07-09 | Boris Tabakoff | Composition and method for reducing blood acetaldehyde levels |
EP0234464A1 (en) * | 1986-02-18 | 1987-09-02 | Takeda Chemical Industries, Ltd. | Composition and method for reducing acetaldehyde toxicity |
JPS62277325A (en) * | 1986-02-18 | 1987-12-02 | Takeda Chem Ind Ltd | Antidote for acetaldehyde |
JPH0374327A (en) * | 1989-08-16 | 1991-03-28 | Ajinomoto Co Inc | Excitometabolic agent for alcohol |
JPH06116144A (en) * | 1992-10-07 | 1994-04-26 | Shuichi Kimura | Composition for preventing alcoholic hepatopathy |
US5922346A (en) * | 1997-12-01 | 1999-07-13 | Thione International, Inc. | Antioxidant preparation |
Non-Patent Citations (3)
Title |
---|
DATABASE WPI Week 199125, Derwent World Patents Index; AN 1991-136895, XP002908014 * |
PATENT ABSTRACTS OF JAPAN * |
VILLE SALASPURO ET AL.: "Removal of acetaldehyde from saliva by a slow-release buccal tablet of l-cysteine", INT. J. CANCER, vol. 97, 2002, pages 361 - 364, XP002908015 * |
Cited By (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9474733B2 (en) | 2000-10-30 | 2016-10-25 | Biohit Oyj | Method and preparation for binding acetaldehyde in saliva, stomach and large intestine |
US6685917B2 (en) | 2000-11-22 | 2004-02-03 | Rxkinetix, Inc. | Treatment of mucositis |
WO2006037848A1 (en) * | 2004-10-08 | 2006-04-13 | Biohit Oyj | Method and preparation for binding aldehydes in saliva |
WO2006103316A1 (en) * | 2005-04-01 | 2006-10-05 | Biohit Oyj | Food composition for binding acetaldehyde in mouth and in digestive track, and method for the preparation of the composition |
CN104172194A (en) * | 2005-04-01 | 2014-12-03 | 拜奥希特公司 | Food composition for binding acetaldehyde in mouth and in digestive track, and method for the preparation of the composition |
EA017831B1 (en) * | 2005-04-01 | 2013-03-29 | Биохит Оий | Food composition for binding acetaldehyde and method for the preparation thereof |
US8227513B2 (en) | 2005-04-01 | 2012-07-24 | Biohit Oyj | Food composition for binding acetaldehyde in mouth and in digestive track, and method for the preparation of the composition |
WO2007009012A2 (en) * | 2005-07-13 | 2007-01-18 | Al Czap | Compositions for oral administration of sustained release glutathione, methods for their production and uses thereof |
WO2007009012A3 (en) * | 2005-07-13 | 2007-04-19 | Al Czap | Compositions for oral administration of sustained release glutathione, methods for their production and uses thereof |
US7501452B2 (en) | 2005-11-30 | 2009-03-10 | Endo Pharmaceuticals Inc. | Treatment of xerostomia |
US20100239663A1 (en) * | 2006-05-22 | 2010-09-23 | Biohit Oyj | Composition for foodstuff for binding acetaldehyde |
WO2007135241A3 (en) * | 2006-05-22 | 2009-09-17 | Biohit Oyj | Composition and method for binding acetaldehyde in stomach |
EA021063B1 (en) * | 2006-05-22 | 2015-03-31 | Биохит Оий | Composition for foodstuff for binding acetaldehyde and use thereof |
WO2007135241A2 (en) * | 2006-05-22 | 2007-11-29 | Biohit Oyj | Composition and method for binding acetaldehyde in stomach |
WO2007135242A1 (en) * | 2006-05-22 | 2007-11-29 | Biohit Oyj | Composition for foodstuff for binding acetaldehyde |
US8758812B2 (en) | 2006-05-22 | 2014-06-24 | Biohit Oyj | Composition for foodstuff for binding acetaldehyde |
EA019832B1 (en) * | 2006-05-22 | 2014-06-30 | Биохит Оий | Composition and method for binding acetaldehyde in stomach |
EA030968B1 (en) * | 2007-09-14 | 2018-10-31 | Биохит Оий | Preparation and a component intended to be added to a tobacco product |
WO2009034232A1 (en) | 2007-09-14 | 2009-03-19 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
AP2894A (en) * | 2007-09-14 | 2014-05-31 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
EP2197436A1 (en) | 2007-09-14 | 2010-06-23 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
US10265278B2 (en) | 2008-01-08 | 2019-04-23 | Aas, Llc | Pharmaceutical compositions and methods utilizing a D-amino acid |
WO2009087615A1 (en) * | 2008-01-09 | 2009-07-16 | Amino Acid Solutions Inc. | Pharmaceutical compositions and methods utilizing a d-amino acid and an antioxidant for treating neuropsychiatric disorders |
WO2013001167A1 (en) * | 2011-06-29 | 2013-01-03 | Biohit Oyj | Non-toxic compositions for decreasing the risk of cancer caused by oral microbes |
WO2013178880A1 (en) | 2012-05-28 | 2013-12-05 | Biohit Oyj | Composition for preventing headaches |
CN108042520A (en) * | 2012-05-28 | 2018-05-18 | 拜奥希特公司 | Prevent the composition of headache |
US10092534B2 (en) | 2012-05-28 | 2018-10-09 | Biohit Oyj | Composition for treating headaches |
TWI660726B (en) * | 2012-05-28 | 2019-06-01 | 芬蘭商拜歐喜公司 | Composition for preventing headaches |
JP2019089842A (en) * | 2012-05-28 | 2019-06-13 | ビオヒット・ユルキネン・オサケユキテュアBiohit Oyj | Compositions for preventing headaches |
RU2698196C2 (en) * | 2012-05-28 | 2019-08-23 | Биохит Оий | Composition for preventing headaches |
EP2950794A4 (en) * | 2013-02-01 | 2016-11-09 | Biohit Oyj | Composition for binding aldehydes in the mouth |
WO2014140410A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Composition for oral administration for binding aldehydes in the gastrointestinal tract |
WO2014140411A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Encapsulated composition for binding aldehydes in the stomach |
WO2015132472A1 (en) | 2014-03-06 | 2015-09-11 | Biohit Oyj | Composition for binding aldehydes and free radicals in the gastrointestinal tract |
Also Published As
Publication number | Publication date |
---|---|
EA009335B1 (en) | 2007-12-28 |
JP4691312B2 (en) | 2011-06-01 |
US9474733B2 (en) | 2016-10-25 |
EP1339394A1 (en) | 2003-09-03 |
AU2002212395A1 (en) | 2002-05-15 |
ES2370811T3 (en) | 2011-12-23 |
CN1486177A (en) | 2004-03-31 |
US20050267042A1 (en) | 2005-12-01 |
JP2004512353A (en) | 2004-04-22 |
CN100467016C (en) | 2009-03-11 |
FI20002392A0 (en) | 2000-10-30 |
ATE522203T1 (en) | 2011-09-15 |
EA200300532A1 (en) | 2003-10-30 |
EP1339394B1 (en) | 2011-08-31 |
FI20002392A (en) | 2002-05-01 |
FI121528B (en) | 2010-12-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1339394B1 (en) | Pharmaceutical preparation for binding acetaldehyde in saliva, stomach and large intestine | |
JP4771565B2 (en) | Sustained release formulation | |
EP0234670B1 (en) | Sustained-release pharmaceutical formulation containing xanthan gum | |
JP5607550B2 (en) | Gastric retentive sustained release dosage form comprising a combination of a non-opioid analgesic and an opioid analgesic | |
EP2389163B1 (en) | Controlled release pharmaceutical or food formulation and process for its preparation | |
FR2518409A1 (en) | SUSTAINED RELEASE THERAPEUTIC PREPARATIONS BASED ON HYDROXYPROPYLMETHYLCELLULOSE | |
KR100322340B1 (en) | Oral cholesterol lowering agents | |
JPH0773480B2 (en) | Amino acid based nutrition pellets | |
JPH08104629A (en) | Form for taking medicine for oral application | |
JP2014122237A (en) | Element and preparation intended to be added to tobacco product | |
EA021063B1 (en) | Composition for foodstuff for binding acetaldehyde and use thereof | |
WO2006115770A2 (en) | Orally disintegrating pharmaceutical tablet formulations of olanzapine | |
KR20150016382A (en) | Composition for preventing headaches | |
CN107835684A (en) | Prevention is still drank after a night the composition of symptom | |
JP5879359B2 (en) | Pharmaceutical compositions comprising citric acid and bicarbonate and their use for treating cystinuria | |
HUE032753T2 (en) | Pharmaceutical composition comprising bicarbonate salt, and use thereof as a medicament in the treatment and/or prevention of urinary lithiasis and related diseases | |
US20110171296A1 (en) | Method and preparation for binding acetaldehyde in saliva, the stomach and the large intestine | |
EP2640365A1 (en) | Pharmaceutical composition comprising krebs cycle precursor salt, in particular citrate salt, and use thereof as a medicament | |
CN101773497A (en) | Compound alpha-keto acid tablet and preparation method thereof | |
AU2011100052A4 (en) | Method and preparartion for binding acetaldehyde in the stomach | |
JP2016514120A (en) | Composition for oral administration for binding aldehydes in the gastrointestinal tract | |
JP2024093842A (en) | Sustained functional food and its manufacturing method | |
JP2002522376A (en) | Compressed composition containing clarified xanthan gum | |
JPH11246392A (en) | Oral solid formulation | |
IE67128B1 (en) | Smoking substitute |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2002538910 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001980581 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 635/KOLNP/2003 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200300532 Country of ref document: EA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 018216285 Country of ref document: CN |
|
WWP | Wipo information: published in national office |
Ref document number: 2001980581 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10415422 Country of ref document: US |