CN101076248A - 使用d－苏型哌甲酯的治疗 - Google Patents
使用d－苏型哌甲酯的治疗 Download PDFInfo
- Publication number
- CN101076248A CN101076248A CNA2005800425053A CN200580042505A CN101076248A CN 101076248 A CN101076248 A CN 101076248A CN A2005800425053 A CNA2005800425053 A CN A2005800425053A CN 200580042505 A CN200580042505 A CN 200580042505A CN 101076248 A CN101076248 A CN 101076248A
- Authority
- CN
- China
- Prior art keywords
- oil
- administration
- salt
- methylphenidate
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- DUGOZIWVEXMGBE-CHWSQXEVSA-N dexmethylphenidate Chemical compound C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-CHWSQXEVSA-N 0.000 title claims abstract description 39
- 229960001042 dexmethylphenidate Drugs 0.000 title claims abstract description 39
- 238000011282 treatment Methods 0.000 title claims description 32
- 238000000034 method Methods 0.000 claims abstract description 50
- -1 erythro methylphenidates Chemical class 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
- 208000000323 Tourette Syndrome Diseases 0.000 claims abstract description 19
- 208000016620 Tourette disease Diseases 0.000 claims abstract description 19
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims description 46
- 238000009472 formulation Methods 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 32
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 14
- 239000000194 fatty acid Substances 0.000 claims description 14
- 229930195729 fatty acid Natural products 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 239000007788 liquid Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- DUGOZIWVEXMGBE-OLZOCXBDSA-N methyl (S)-phenyl[(R)-piperidin-2-yl]acetate Chemical compound C([C@@H]1[C@@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-OLZOCXBDSA-N 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000012459 cleaning agent Substances 0.000 claims description 9
- 239000003921 oil Substances 0.000 claims description 9
- 235000019198 oils Nutrition 0.000 claims description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 8
- 230000003188 neurobehavioral effect Effects 0.000 claims description 8
- 150000004665 fatty acids Chemical class 0.000 claims description 7
- 230000004044 response Effects 0.000 claims description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003599 detergent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 230000006735 deficit Effects 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 230000010349 pulsation Effects 0.000 claims description 4
- 239000000344 soap Substances 0.000 claims description 4
- 239000000375 suspending agent Substances 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 239000000730 antalgic agent Substances 0.000 claims description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
- 230000003920 cognitive function Effects 0.000 claims description 3
- 239000003995 emulsifying agent Substances 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 210000003205 muscle Anatomy 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical group FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019483 Peanut oil Nutrition 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 239000010775 animal oil Substances 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 125000002091 cationic group Chemical group 0.000 claims description 2
- 235000005687 corn oil Nutrition 0.000 claims description 2
- 239000002285 corn oil Substances 0.000 claims description 2
- 235000012343 cottonseed oil Nutrition 0.000 claims description 2
- 239000002385 cottonseed oil Substances 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 2
- 229940093471 ethyl oleate Drugs 0.000 claims description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methyl alcohol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002480 mineral oil Substances 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 239000004006 olive oil Substances 0.000 claims description 2
- 235000008390 olive oil Nutrition 0.000 claims description 2
- 239000000312 peanut oil Substances 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 claims description 2
- 239000012266 salt solution Substances 0.000 claims description 2
- 239000008159 sesame oil Substances 0.000 claims description 2
- 235000011803 sesame oil Nutrition 0.000 claims description 2
- 239000001593 sorbitan monooleate Substances 0.000 claims description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 claims description 2
- 229940035049 sorbitan monooleate Drugs 0.000 claims description 2
- 239000003549 soybean oil Substances 0.000 claims description 2
- 235000012424 soybean oil Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 2
- 229940099259 vaseline Drugs 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims 1
- 230000001149 cognitive effect Effects 0.000 claims 1
- 239000004519 grease Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 abstract description 13
- 229960001344 methylphenidate Drugs 0.000 abstract description 13
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 208000035475 disorder Diseases 0.000 abstract description 2
- 208000016686 tic disease Diseases 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 229940079593 drug Drugs 0.000 description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 11
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 11
- 239000002775 capsule Substances 0.000 description 8
- 230000036461 convulsion Effects 0.000 description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 6
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 6
- 206010028347 Muscle twitching Diseases 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 239000002269 analeptic agent Substances 0.000 description 3
- 230000003555 analeptic effect Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003405 delayed action preparation Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 240000004859 Gamochaeta purpurea Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 206010029216 Nervousness Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000008234 Tics Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 235000021251 pulses Nutrition 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- GHUXAYLZEGLXDA-UHFFFAOYSA-N 8-azido-5-ethyl-6-phenylphenanthridin-5-ium-3-amine;bromide Chemical compound [Br-].C12=CC(N=[N+]=[N-])=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 GHUXAYLZEGLXDA-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010027304 Menopausal symptoms Diseases 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920006184 cellulose methylcellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- DUGOZIWVEXMGBE-STQMWFEESA-N methyl (S)-phenyl[(S)-piperidin-2-yl]acetate Chemical compound C([C@H]1[C@@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-STQMWFEESA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000007889 pulsatile dosage form Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- GIZSHQYTTBQKOQ-UHFFFAOYSA-N threo-Syringoylglycerol Chemical compound COC1=CC(C(O)C(O)CO)=CC(OC)=C1O GIZSHQYTTBQKOQ-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
Classifications
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
本发明公开了对能响应哌甲酯和/或其一种或多种异构体给药的疾病的治疗方法，所述方法包括鉴别罹患具有家族史和诊断的抽搐或Tourette综合征疾病或病症的患者，并给药所述患者治疗有效量的、基本不含1－苏型异构体和赤型哌甲酯的D－苏型哌甲酯。
Description
相关申请的交叉参考
本申请要求2004年12月9日提交的美国申请No.60,634,562的优选权，其公开的全文合并于此作为参考。
技术领域
本发明特别涉及对一类罹患Tourette综合征的患者的治疗方法，所述患者还罹患能响应D-苏型哌甲酯或其盐(例如，盐酸D-苏型哌甲酯)给药的疾病。本发明还公开了给药所述患者治疗有效量的基本上没有1-苏型异构体和没有赤型哌甲酯的D-苏型哌甲酯的方法。
背景技术
Tourette综合征是严重的神经病症，其特征为面部和其它身体部位的多处抽搐，通常发病于儿童或青少年，并经常伴随咕哝和强迫性发声。其症状通常是孩子在小学时，始发于青春期后许多生长过快的状况。虽然Tourette综合征没有治愈方法，但是药物可以缓解部分症状。
抽搐是突发的迅速而重复的运动(运动抽搐)或发声(发声抽搐)。运动抽搐通常涉及面部或上身单一部位的肌肉。抽搐有两种主要类型。单纯性抽搐涉及一组肌肉-例如，摇头、眨眼、吸鼻、伸颈、耸肩和面部扭曲。复合型抽搐涉及超过一组肌肉-例如，击打自己或咬自己、蹦跳、和走路时旋转。
抽搐有时随时间从一种单纯型抽搐向另一种发展或者从单纯型向复合型发展。另外，有些抽搐缓慢而持续而不是短暂而迅速，有些抽搐涉及下身。发声抽搐也可以是单纯型(咳嗽、清嗓、咆哮)或复合型(反复叙述事情、重复他人的话、说秽语)。
抽搐被认为是影响身体运动系统的遗传性神经病。抽搐也能由头部受伤或药物如某些类型的刺激物引起。患有抽搐病的人主诉在抽搐发作前，体内有急迫的满积感。这种满积感称为前兆。抽搐的人经常在抽搐结束后感到轻松。虽然抽搐是不自觉的，但用自觉的努力有时能短时间抑制急迫感。抽搐的爆发经常在自觉的抑制之后，以减轻内在的满积感。
罹患Tourette综合征或抽搐者也能患有其它病恙，包括注意力缺陷障碍(ADD)、注意力缺陷多动障碍(ADHD)、和/或一种或多种认知功能降低、疲倦和/或与给药止痛剂无关，但可能与潜伏的癌症、癌症的治疗、或这两者有关的神经性行为减慢。例如，一些内科医生估计，超过50％的Tourette综合征患者也患有ADHD。
中枢神经系统(CNS)兴奋剂经常被处方用于治疗ADHD。目前，这些兴奋剂禁用于下列类型的患者：(a)罹患Tourette综合征或抽搐和/或(b)具有Tourette综合征或抽搐的家族史。Tourette综合征也被认为是施用盐酸哌甲酯药物的不良反应。过去，某些参考文献提出，患有抽搐、Tourette综合征或者有Tourette综合征或抽搐家族史的患者，不应采用含有哌甲酯的药物。本发明特别涉及对患有抽搐、Tourette综合征或者有Tourette综合征或抽搐家族史的患者施用哌甲酯。
哌甲酯表现出如下的四个单独的光学异构体：
1-苏型 d-赤型
d-苏型 1-赤型
其中R2是苯基。药学可接受的盐通常可以临床给药。
哌甲酯的苏型外消旋体(对映异构体对)是中枢神经系统的轻度兴奋剂，药理活性从定性上类似于苯丙胺。与应用哌甲酯的DL-苏型消旋体有关的不希望的副作用包括食欲减退、体重减轻、失眠、头晕和烦躁。此外，该消旋体是II类控制物质，其在静脉给药或通过吸入或摄入给药能产生欣快作用，从而意味着高度的滥用可能性。
DL-苏型哌甲酯的缓释制剂已经产生，其提供了药物以日为时程的缓慢释放。但是，已经发现，使用缓释制剂时，与全天给药常规剂型比较，药物的峰血浆浓度降低了。在一些研究中，DL-苏型哌甲酯的缓释制剂已显示出比常规剂型的疗效低。
脉冲释放剂型，其中单一的剂型中含有两种剂量，一种在摄入后即刻释放，另一种在延迟数小时后释放，该剂型最近已被提议作为最高有效性给药方案的方法。虽然脉冲剂型提供了多剂药物在预定时间间隔的有效释放，但这种剂型可能制造起来很复杂并且昂贵。无论如何，我们需要对所有的患者给药最有效用和疗效的药剂，在哌甲酯的情况下，现已相信，通过给药单一有效的异构体，即D-苏型哌甲酯，这种目的可以最佳实现。
已经发现，使用哌甲酯的D-苏型异构体(2R:2′R)，其基本上不含1-苏型异构体和赤型哌甲酯，能产生保持高度活性水平并同时具有降低欣快作用和减少患者滥用可能性的哌甲酯药物。参见美国专利No.5,908,850，其全文合并在此作为参考。因此，D-苏型哌甲酯(2R:2′R)可以具有治疗活性提高而副作用降低，而L-苏型哌甲酯可在患者中产生不需要的副作用、欣快感和药物滥用。
对于改进罹患Tourette综合征合并患有另一种能反应D-苏型哌甲酯的病症的患者的治疗方法，有持续的需要。本发明涉及这些目的，以及其它重要目的。
发明概述
不受理论的局限，本发明部分涉及这样一种假设，即基本上不含1-苏型异构体和赤型哌甲酯的D-苏型哌甲酯，可以安全施用于一类患者，所述患者罹患了Tourette综合征和/或抽搐，连同ADD、ADHD或其它可以响应给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯的病症。其它病症可包括一种或多种认知功能、疲倦以及与给药止痛剂无关，但可能与潜在的癌症、癌症治疗、或这两者有关的神经行为减慢的疾病。本发明公开了治疗一类患者的方法，而不是仅仅涵盖了治疗某些适应症。为此目的，公开的是对给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯有响应的疾病或病症的治疗方法，所述方法包括，鉴别罹患所述疾病或病症以及有抽搐或Tourette综合征家族史或诊断的患者，并给药所述患者包含治疗有效量的、基本上不含1-苏型异构体和赤型哌甲酯的D-苏型哌甲酯的剂型。其它实施方案是对诊断患有注意力缺陷障碍或注意力缺陷多动障碍并出现抽搐或具有Tourette综合征家族史的患者的治疗方法，包括鉴别患者和给药所述患者包含治疗有效量的、基本上不含1-苏型异构体和赤型哌甲酯的D-苏型哌甲酯的剂型。
在本发明的一些实施方案中，治疗有效量是D-苏型哌甲酯的单次有效量(bolus)剂量。在实施方案中适于口服给药的剂型可以是优选的。有效量可以皮下、静脉内、肌内或腹膜内给药。在一些实施方案中，给药也可以借助于选自无菌液体或液体混合物、醇类、二元醇类、甘油缩酮类和醚类的药物载体。
还有可以优选的实施方案，其中有效量是0.01重量％D-苏型哌甲酯或其盐。在一些实施方案中，剂型可以具有选自羧甲基纤维素钠、山梨醇、右旋糖苷和稳定剂的粘度增加物质。在其它实施方案中，单次有效量剂型可以是患者体重的大约0.01mg/kg-大约1mg/kg或者大约0.1mg/kg-大约0.5mg/kg。单次有效量剂型也可令人理解含有药学可接受的载体。也可以领会脉动剂型(pulsatile dosage forms)适用于本发明。
具体的优选实施方案
本发明一方面提供了对这样一类患者的治疗方法，他们同时患有(a)Tourette综合征和/或抽搐以及(b)另一种响应给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯的病症。该方法包括鉴别患有疾病或病症的患者，例如注意力缺陷障碍或注意力缺陷多动障碍，和具有抽搐或Tourette综合征的家族史或诊断，并给药所述患者治疗有效量的基本上不含1-苏型异构体和赤型哌甲酯的D-苏型哌甲酯。D-苏型哌甲酯可以单剂、单次有效量剂量给药，每24小时给药一剂。药物也可以脉动剂型或以产生两种药物剂量的剂型给药。
对给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯有响应的疾病，记载于美国专利No.6,486,177中，该专利已转让给本申请的受让人，并以其全文合并在此作为参考。它们可包括疲倦、神经行为减慢、和从癌症或从其治疗如化疗、放疗、施用控制疼痛的药物所产生的神经行为减慢、以及从治疗肿瘤病症的给药引起的神经行为减慢。其它疾病包括绝经期症状、认知功能障碍引起的沮丧(“认识副作用”)和癌症相关的疲倦、以及对此的治疗。肿瘤病症的治疗可以认为是控制疼痛的给药和生物治疗，包括减轻疼痛的药物、化疗、放疗和手术。在一些特别优选的实施方案中，肿瘤病症的治疗是化疗或施用减轻疼痛的药物。在公开方法的其它实施例中，减轻疼痛的药物是一种或多种阿片止痛剂、神经阻滞剂或其它精神调节剂。对给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯有响应的其它疾病，可以是某些类型的与患有获得性免疫缺陷综合症(AIDS)或AIDS相关病症包括但不限于AIDS-相关的痴呆的患者有关的认知下降，包括在美国专利No.6,602,887中，这里以其全文合并作为参考。
对给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯有响应的疾病，也可以包括，例如ADD和ADHD，概述于美国专利No.6,528,530，这里以其全文合并作为参考。
对给药D-苏型哌甲酯或其盐例如盐酸D-苏型哌甲酯有响应的疾病，也可以包括，例如与绝经期有关的症状，包括血管舒缩不稳定、神经质、兴奋性、疲倦、神经行为减慢、冷淡、精神沮丧和短期记忆受损，概述于美国专利6,486,177，这里以其全文合并作为参考。
根据本发明的一种方法，给药基本上不含1-苏型异构体和赤型哌甲酯的D-苏型哌甲酯的单次有效量剂型。“基本不含”，用在本文指存在化合物的一种光学异构体，而几乎或完全排除所述化合物的任何其它光学异构体。例如，在本发明的背景下，如果剂型内D-苏型哌甲酯的量代表了剂型中哌甲酯总量的至少约95％、至少约96％、至少约97％、至少约98％、或至少约99％，则D-苏型哌甲酯在剂型内“基本不含”哌甲酯的其他光学异构体。D-苏型可以通过本领域技术人员已知的方法分离。
“长期的”，用在本文指为了治疗需要治疗的患者的神经疾病的目的，持续、规律、长期地治疗性给药，即基本不中断的定期给药，例如每天，为期至少数周或数月至数年。
“单次有效量(bolus)”，用于本文指作为单一事件的给药。术语“单次有效量”意在排除如缓释、脉冲释放和时间释放的剂型，并包括任何能用于递送单一剂量的剂型。根据本发明，一个单次有效量优选每天一次给药需要治疗的患者，更优选在早晨。本发明的单次有效量剂量可以用本领域技术人员已知的任何传统形式给药。适用的给药方法包括口服剂型、注射和输注。哌甲酯药物的单次有效量剂型由，例如，美国专利No.6,602,887教导，这里以其全文合并作为参考。
本发明的方法也可以按照授予Mehta等的美国专利No.5,837,284的记载而实行，该专利已转让给本申请的受让人，这里以其全文合并作为参考。在这样的剂型中，第一剂量的释放优选即刻发生，例如，释放可以发生在给药后约30分钟内。在很少或基本上没有药物释放的时间后，第二剂量释放。这样的释放图形可以称为“脉动”。
第一剂量的释放可以在摄入后大约半小时内，优选约15分钟内，更优选摄入后约5分钟内。第二剂量，或延迟释放，可包括在此期间特定剂型的药物释放不超过约10％的一段时间，之后是大约0.5小时至大约2.5小时的一段时间，优选大约1.5小时，更优选大约1小时，其中不少于约70％，优选不少于约80％，更优选不少于约90％的药物被释放。如果需要，在使用适当的剂型的情况下，可以按照某些实施方案进行第三次释放。因此，本方法中可以采用提供3个或多个剂量的剂型。
脉动剂型递送的剂量在许多途径中可以不同。例如，第一剂量可以提供患者的日处方药物摄入量的大约30％至大约70％，第二剂量提供大约70％至大约30％。如果需要两个近似等同的剂量，初始剂量优选提供患者药物的日处方摄入量的大约40％至大约60％，第二剂量优选提供大约60％至大约40％。需要的话，第一剂量和第二剂量可以各提供患者药物的日处方摄入量的大约50％。但是，对于本领域技术人员显见的是，体内药物代谢的作用可能需要调整各剂量的相对量，使得，例如，第二剂量可以调整为比第一剂量提供更多的药物，以补偿药物释放和药物代谢之间的任何竞争。
延迟剂型可以用本领域已知的方法实现。通过使用某些被称作“季胺基甲基丙烯酸酯共聚物”的共聚物，它们可以部分被提供。季胺基甲基丙烯酸酯共聚物包括丙烯酸酯基和/或甲基丙烯酸酯基连同季铵基。该共聚物可以掺入制剂中，用于涂敷含有药物的粒子。
用于本发明方法中的丙烯酸酯基和/或甲基丙烯酸酯基可以称作“丙烯酸基”。丙烯酸基优选源于选自丙烯酸的C1-C6烷基酯和甲基丙烯酸的C1-C6烷基酯。可以优选丙烯酸的C1-C6烷基酯和甲基丙烯酸的C1-C6烷基酯。适用的单体包括，例如，丙烯酸甲酯、丙烯酸乙酯、甲基丙烯酸甲酯和甲基丙烯酸乙酯。优选丙烯酸乙酯和甲基丙烯酸甲酯，高度优选含有丙烯酸乙酯和甲基丙烯酸甲酯的共聚物。还优选所述共聚物的分子量约150,000。
在用单次有效量剂型的实施方案中，这里描述的化合物可以采用药学可接受的载体，例如，溶液、悬液、片剂、胶囊、油膏、酏剂和可注射复合物。药物制剂通常能含有大约1重量％至大约90重量％的活性成分。单一剂量形式的制剂，“单位剂型”，优选含有约20％至约90％活性成分。术语“活性成分”用在本文指本文所述的化合物、其盐、以及本文所述的化合物与其它药物活性化合物的混合物。剂量单位形式，例如，片剂或胶囊，通常含有大约0.001g至大约1.0g的活性成分。药物制剂可以口服、胃肠外或局部给药。
含有本文所述的药物制剂可以通过本领域技术人员已知的方法制备，例如，常规混合、粒化、溶解或冻干。口服剂型包括胶囊、丸剂、片剂、锭剂、菱形片、熔体、粉末、溶液、悬液和乳液。本发明提供的口服剂型可以是片剂、胶囊等的形式并可以是任何适合口服给药的形状，如球形、立方形、椭圆、豆形或椭球形。对于口服剂型，例如，化合物可以与一种或多种固体的药物可接受载体结合，任选粒化产生的混合物。可以任选包括一种或多种药学可接受的助剂，例如，流动调节剂和润滑剂。适用的载体包括，例如，填料乳糖、纤维素制剂、磷酸钙、以及粘合剂如甲基纤维素、羟甲基纤维素，和淀粉如玉米淀粉、土豆淀粉、大米淀粉和小麦淀粉。剂型可以是颗粒的形式，其可以是不规则的形状。剂型可以包括含有粒子的胶囊。可以口服给药的药物制剂的例子是明胶组成的干填充的胶囊，和明胶和增塑剂如甘油或山梨醇组成的软密封的胶囊。干填充胶囊可以含有例如在与填料、粘合剂、助流剂和稳定剂的混合物中的颗粒形式的活性成分。在软胶囊中，活性成分优选溶解或悬浮在适当的液体助剂中，例如脂肪油、石蜡油、或液体聚乙二醇，任选存在稳定剂。其它可口服给药的形式包括含有活性成分的糖浆，例如，浓度约0.01％-20％的悬浮形式，或者是给药时能在大约2至大约5毫升的量中提供适当的单次剂量的类似浓度。用于口服液体剂型的适当的赋形剂包括稀释剂如水和醇类，例如乙醇、苯甲醇和聚乙二醇，带有或不带有药学可接受的表面活性剂、助悬剂或乳化剂。适用的还有与液体如奶结合的粉末状或液体浓缩物。这样的浓缩物也可以装入单次剂量。
本文所述的混合物可以是胃肠外给药的，即，皮下、静脉内、肌肉内或腹膜内，作为化合物在带有药物载体的生理可接受的稀释剂中的可注射剂。胃肠外给药的溶液可以是输注溶液的形式。药物载体可以是，例如，无菌液体或液体例如水、盐水、右旋糖水溶液和相关的糖溶液、醇如乙醇、二醇如丙二醇或聚乙二醇、甘油缩酮如2，2-二甲基-1，3-二氧戊烷-4-甲醇、醚如聚(乙二醇)400、油、脂肪酸、脂肪酸酯或甘油酯的混合物，可以加入或不加入药学可接受的表面活性剂如肥皂或清洁剂、助悬剂如果胶、卡波姆、甲基纤维素、羟丙甲基纤维素或羧甲基纤维素、或者乳化剂或其他药学可接受的助剂。可以用于胃肠外制剂的油的例子包括石油、动物油、植物油、或合成油，例如花生油、大豆油、芝麻油、棉籽油、玉米油、橄榄油、矿脂和矿物油。适用的脂肪酸包括，例如，油酸、硬脂酸和异硬脂酸。适用的脂肪酸酯包括油酸乙酯和豆蔻酸异丙酯。适用的皂类包括脂肪酸碱金属盐、铵盐和三乙醇胺盐。适用的清洁剂包括阳离子清洁剂如二甲基二烷基卤化铵和卤化烷基吡啶鎓盐；阴离子清洁剂如烷基、芳基和烯烃磺酸盐、甘油一酸酯硫酸盐和磺基琥珀酸酯盐；非离子清洁剂如脂肪胺氧化物、脂肪酸烷醇酰胺和聚氧乙烯丙烯共聚物；和两性清洁剂如烷基-(-氨基丙酸酯和2-烷基咪唑啉季铵盐；以及清洁剂的混合物。胃肠外制剂通常在溶液中可含有至少约0.01重量％的活性成分。也可以有利应用防腐剂和缓冲剂。注射悬液可以包括粘度增加物质，例如，羧甲基纤维素钠、山梨醇或右旋糖苷，还能包括稳定剂。为了使注射部位的刺痛最小化，可注射的组合物可含有非离子的表面活性剂，亲水-亲脂平衡(HLB)为约12至约17。所述制剂中表面活性剂的量为约5重量％至约15重量％。表面活性剂可以是具有超过HLB的单一成分或者具有所需HLB的两种或多种成分的混合物。适用的表面活性剂的具体例子包括聚乙烯山梨糖醇酐脂肪酸酯，例如，山梨糖醇酐单油酸酯。
用于治疗具体患者的剂量中，D-苏型哌甲酯的优选量可以很容易地由本领域技术人员确定。确定适当的剂量的因素包括，例如，患者的体重和年龄、药治疗的疾病的类型和程度、和患者的其它情况包括其它疾病和患者可能采用的其它药物。通常，D-苏型哌甲酯的剂量为约0.01mg/kg患者体重至约1mg/kg患者体重。适用量可以由本领域技术人员确定。例如，相对小的儿童通常需要大约0.03至大约0.3mg/kg的剂量，而较大的儿童或成人需要大约0.1mg/kg至大约0.4或0.5mg/kg。
Claims (29)
1.治疗对给药D-苏型哌甲酯或其盐有响应的疾病或病症的方法，所述方法包括下述步骤：
-鉴别罹患所述疾病或病症以及罹患Tourette综合征或抽搐或者具有Tourette综合征或抽搐家族史的患者；和
-给药所述患者包括治疗有效量D-苏型哌甲酯或其盐的剂型，所述D-苏型哌甲酯基本不含1-苏型异构体及其盐和赤型哌甲酯及其盐。
2.权利要求1的方法，其中所述治疗有效量是单次有效剂量。
3.权利要求1的方法，其中所述剂型适合口服给药。
4.权利要求1的方法，其中所述给药是皮下、静脉内、肌肉内或腹膜内。
5.权利要求1的方法，其中所述给药借助于选自无菌液体或液体的混合物、醇类、二元醇类、甘油缩酮类和醚类的药物载体。
6.权利要求5的方法，其中所述无菌液体或液体的混合物是水、盐水、右旋糖水溶液、或相关的糖溶液。
7.权利要求5的方法，其中所述醇是乙醇。
8.权利要求5的方法，其中所述二元醇是丙二醇或聚乙二醇。
9.权利要求5的方法，其中所述甘油缩酮是2，2-二甲基-1，3-二氧戊烷-4-甲醇。
10.权利要求5的方法，其中所述醚是聚(乙二醇)400、油、脂肪酸、脂肪酸酯或甘油酯。
11.权利要求10的方法，进一步包括至少一种药学可接受的表面活性剂、助悬剂、乳化剂、或其它药学可接受的助剂。
12.权利要求11的方法，其中所述表面活性剂是皂类、清洁剂、或清洁剂的混合物。
13.权利要求11的方法，其中所述助悬剂是果胶、卡波姆、甲基纤维素、羟丙甲基纤维素或羧甲基纤维素。
14.权利要求10的方法，其中所述油选自石油、动物油、植物油、或合成油。
15.权利要求14的方法，其中所述油是花生油、大豆油、芝麻油、棉籽油、玉米油、橄榄油、矿脂、或矿物油。
16.权利要求10的方法，其中所述脂肪酸选自油酸、硬脂酸和异硬脂酸。
17.权利要求10的方法，其中所述脂肪酸酯选自油酸乙酯和豆蔻酸异丙酯。
18.权利要求12的方法，其中所述皂类是脂肪酸的碱金属盐、铵盐和三乙醇胺盐。
19.权利要求12的方法，其中所述清洁剂选自阳离子清洁剂、阴离子清洁剂、非离子清洁剂和两性清洁剂。
20.权利要求19的方法，其中所述清洁剂是二甲基二烷基卤化铵、卤化烷基吡啶鎓盐、烷基、芳基和烯烃的磺酸盐、甘油一酸酯硫酸盐、磺基琥珀酸酯盐、脂肪胺氧化物、脂肪酸烷醇酰胺、聚氧乙烯丙烯共聚物、烷基-氨基丙酸酯、或2-烷基咪唑啉季铵盐。
21.权利要求1的方法，其中所述治疗有效量是0.01重量％的D-苏型哌甲酯或其盐。
22.权利要求1的方法，进一步包括施用选自羧甲基纤维素钠、右旋糖苷的粘度增加物质和稳定剂。
23.权利要求11的方法，其中所述表面活性剂占剂型的大约5重量％至大约15重量％。
24.权利要求11的方法，其中所述表面活性剂选自聚乙烯山梨糖醇酐脂肪酸酯。
25.权利要求24的方法，其中表面活性剂是山梨糖醇酐单油酸酯。
26.权利要求1的方法，其中所述疾病是注意力缺陷多动障碍、与绝经期有关的症状、或一种或多种认知功能降低、疲倦、和与给药止痛剂无关，但可能与潜伏的癌症、癌症的治疗、或这两者有关的神经行为减慢。
27.权利要求1的方法，其中所述疾病是疲倦、和从癌症或从其治疗如化疗、放疗、施用控制疼痛的药物所产生的神经行为减慢和认知副作用、或者从治疗肿瘤病症的给药引起的神经行为减慢。
28.权利要求1的方法，其中所述给药是通过脉动剂型。
29.权利要求1的方法，其中所述剂型提供了药物的两种剂量。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63456204P | 2004-12-09 | 2004-12-09 | |
| US60/634,562 | 2004-12-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101076248A true CN101076248A (zh) | 2007-11-21 |
Family
ID=36578626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005800425053A Pending CN101076248A (zh) | 2004-12-09 | 2005-12-08 | 使用d－苏型哌甲酯的治疗 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20060127421A1 (zh) |
| EP (1) | EP1830648A4 (zh) |
| JP (1) | JP2008523097A (zh) |
| KR (1) | KR20070087643A (zh) |
| CN (1) | CN101076248A (zh) |
| AR (1) | AR053655A1 (zh) |
| AU (1) | AU2005313887B2 (zh) |
| BR (1) | BRPI0517166A (zh) |
| CA (1) | CA2591247A1 (zh) |
| IL (1) | IL183746A0 (zh) |
| NZ (1) | NZ555842A (zh) |
| WO (1) | WO2006063256A2 (zh) |
| ZA (1) | ZA200705560B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106959367A (zh) * | 2009-10-30 | 2017-07-18 | 协和梅迪克斯株式会社 | 用于测定样本中的待测定成分的方法和试剂盒 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090076079A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched methylphenidate |
| US20100249248A1 (en) * | 2007-10-24 | 2010-09-30 | Suntory Holdings Limited | LIGAND AGENTS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARs) |
| WO2015188092A1 (en) * | 2014-06-06 | 2015-12-10 | Rhodes Pharmaceuticals, L.P. | Methods for treating attention deficit hyperactivity disorder with methylphenidate |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2507631A (en) * | 1944-01-19 | 1950-05-16 | Ciba Pharm Prod Inc | Pyridine and piperidine compounds and process of making same |
| US2957880A (en) * | 1953-12-23 | 1960-10-25 | Ciba Pharm Prod Inc | Process for the conversion of stereoisomers |
| US2838519A (en) * | 1953-12-23 | 1958-06-10 | Ciba Pharm Prod Inc | Process for the conversion of stereoisomers |
| US4137300A (en) * | 1976-08-20 | 1979-01-30 | Ciba-Geigy Corporation | Sustained action dosage forms |
| US4410700A (en) * | 1980-07-03 | 1983-10-18 | The United States Of America As Represented By The Department Of Health And Human Services | Preparation of chiral 1-benzyl-1,2,3,4-tetrahydroisoquinolines by optical resolution |
| GB2112730B (en) * | 1981-09-30 | 1985-12-18 | Nat Res Dev | Encapsulated particles |
| US4904476A (en) * | 1986-03-04 | 1990-02-27 | American Home Products Corporation | Formulations providing three distinct releases |
| US4794001A (en) * | 1986-03-04 | 1988-12-27 | American Home Products Corporation | Formulations providing three distinct releases |
| US4986987A (en) * | 1986-05-09 | 1991-01-22 | Alza Corporation | Pulsed drug delivery |
| US4992445A (en) * | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5114946A (en) * | 1987-06-12 | 1992-05-19 | American Cyanamid Company | Transdermal delivery of pharmaceuticals |
| US5236689A (en) * | 1987-06-25 | 1993-08-17 | Alza Corporation | Multi-unit delivery system |
| US5391381A (en) * | 1987-06-25 | 1995-02-21 | Alza Corporation | Dispenser capable of delivering plurality of drug units |
| US5283193A (en) * | 1988-06-27 | 1994-02-01 | Asahi Kasei Kogyo K.K. | Process for producing optically active α-substituted organic acid and microorganism and enzyme used therefor |
| SE509029C2 (sv) * | 1988-08-16 | 1998-11-30 | Ss Pharmaceutical Co | Långtidsverkande diklofenak-natriumpreparat |
| US5202128A (en) * | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5217718A (en) * | 1989-08-18 | 1993-06-08 | Cygnus Therapeutic Systems | Method and device for administering dexmedetomidine transdermally |
| US5284769A (en) * | 1989-10-16 | 1994-02-08 | Chiros Ltd. | Process for preparing a single enantiomer of a lactam using lactamase |
| US5362755A (en) * | 1990-01-05 | 1994-11-08 | Sepracor, Inc. | Method for treating asthma using optically pure (R)-albuterol |
| US5229131A (en) * | 1990-02-05 | 1993-07-20 | University Of Michigan | Pulsatile drug delivery system |
| US5158777A (en) * | 1990-02-16 | 1992-10-27 | E. R. Squibb & Sons, Inc. | Captopril formulation providing increased duration of activity |
| JP2558396B2 (ja) * | 1990-06-28 | 1996-11-27 | 田辺製薬株式会社 | 放出制御型製剤 |
| US5104899A (en) * | 1990-08-13 | 1992-04-14 | Sepracor, Inc. | Methods and compositions for treating depression using optically pure fluoxetine |
| US5232705A (en) * | 1990-08-31 | 1993-08-03 | Alza Corporation | Dosage form for time-varying patterns of drug delivery |
| US5156850A (en) * | 1990-08-31 | 1992-10-20 | Alza Corporation | Dosage form for time-varying patterns of drug delivery |
| US5160744A (en) * | 1991-06-27 | 1992-11-03 | Alza Corporation | Verapmil therapy |
| US5326570A (en) * | 1991-07-23 | 1994-07-05 | Pharmavene, Inc. | Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine |
| DE69229881T2 (de) * | 1991-10-04 | 1999-12-09 | Yoshitomi Pharmaceutical Industries, Ltd. | Tablette mit verzögerter freisetzung |
| DE69222006T2 (de) * | 1991-10-30 | 1998-01-22 | Glaxo Group Ltd | Mehrschichtzusammensetzungen enthaltend Histamin- oder Serotonin- Antagonisten |
| US5580578A (en) * | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
| US5223265A (en) * | 1992-01-10 | 1993-06-29 | Alza Corporation | Osmotic device with delayed activation of drug delivery |
| US5308348A (en) * | 1992-02-18 | 1994-05-03 | Alza Corporation | Delivery devices with pulsatile effect |
| US5331000A (en) * | 1992-03-09 | 1994-07-19 | Sepracor Inc. | Antipyretic and analgesic methods and compositions containing optically pure R(-) ketoprofen |
| US5424950A (en) * | 1992-06-02 | 1995-06-13 | Honeywell Inc. | Vehicle control surface position feedback compensator for reducing vehicle oscillation |
| US5299121A (en) * | 1992-06-04 | 1994-03-29 | Medscreen, Inc. | Non-prescription drug medication screening system |
| US5512293A (en) * | 1992-07-23 | 1996-04-30 | Alza Corporation | Oral sustained release drug delivery device |
| ES2257757T3 (es) * | 1992-08-03 | 2006-08-01 | Sepracor Inc. | Carboxilato de terfenadina y el tratamiento de trastornos alergicos. |
| US5376384A (en) * | 1992-12-23 | 1994-12-27 | Kinaform Technology, Inc. | Delayed, sustained-release pharmaceutical preparation |
| JP3091618B2 (ja) * | 1993-01-29 | 2000-09-25 | 四郎 小林 | 開環重合法および開環重合用酵素触媒 |
| DE9303805U1 (de) * | 1993-03-15 | 1993-06-09 | Blumenkron, Jorge Lopez, Puebla | Flexibler Flüssigkeitstank |
| JP2916978B2 (ja) * | 1993-08-25 | 1999-07-05 | エスエス製薬株式会社 | 放出開始制御型製剤 |
| US5500227A (en) * | 1993-11-23 | 1996-03-19 | Euro-Celtique, S.A. | Immediate release tablet cores of insoluble drugs having sustained-release coating |
| US5567441A (en) * | 1995-03-24 | 1996-10-22 | Andrx Pharmaceuticals Inc. | Diltiazem controlled release formulation |
| GB9514451D0 (en) * | 1995-07-14 | 1995-09-13 | Chiroscience Ltd | Sustained-release formulation |
| MXPA98000395A (es) * | 1995-07-14 | 2005-04-29 | Medeva Europ Ltd | Composicion que comprende d-treo-metilfenidato y otra droga. |
| US6486177B2 (en) * | 1995-12-04 | 2002-11-26 | Celgene Corporation | Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate |
| US6355656B1 (en) * | 1995-12-04 | 2002-03-12 | Celgene Corporation | Phenidate drug formulations having diminished abuse potential |
| US5733756A (en) * | 1996-01-05 | 1998-03-31 | Celgene Corporation | Lactams and processes for stereoselective enrichment of lactams, amides, and esters |
| US5922736A (en) * | 1995-12-04 | 1999-07-13 | Celegene Corporation | Chronic, bolus administration of D-threo methylphenidate |
| US5908850A (en) * | 1995-12-04 | 1999-06-01 | Celgene Corporation | Method of treating attention deficit disorders with d-threo methylphenidate |
| US5837284A (en) * | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US6242464B1 (en) * | 1996-01-22 | 2001-06-05 | Chiroscience Limited | Single isomer methylphenidate and resolution process |
| JP2000504008A (ja) * | 1996-02-02 | 2000-04-04 | メデバ・ユアラプ・リミテッド | Ｄ―トレオ―（ｒ，ｒ）―メチルフェニデートの調製およびエピメリゼーションによる不要エナンチオマーリサイクルの方法 |
| GB9604943D0 (en) * | 1996-03-08 | 1996-05-08 | Chiroscience Ltd | Resolution |
| GB9606417D0 (en) * | 1996-03-27 | 1996-06-05 | Chiroscience Ltd | Asymmetric cyclisation |
| GB9700912D0 (en) * | 1997-01-17 | 1997-03-05 | Chiroscience Ltd | Resolution |
| US5965734A (en) * | 1997-01-31 | 1999-10-12 | Celgene Corporation | Processes and intermediates for preparing 2-substituted piperidine stereoisomers |
| US5936091A (en) * | 1997-05-22 | 1999-08-10 | Celgene Corporation | Processes and intermediates for resolving piperidyl acetamide stereoisomers |
| US6962997B1 (en) * | 1997-05-22 | 2005-11-08 | Celgene Corporation | Process and intermediates for resolving piperidyl acetamide steroisomers |
| CA2653839A1 (en) * | 1998-11-02 | 2000-05-11 | John G. Devane | Multiparticulate modified release composition |
| US6395752B1 (en) * | 1999-03-04 | 2002-05-28 | Pharmaquest Limited | Method of treating depression using 1-threo-methylphenidate |
| US6127385A (en) * | 1999-03-04 | 2000-10-03 | Pharmaquest Limited | Method of treating depression using l-threo-methylphenidate |
| US20030170181A1 (en) * | 1999-04-06 | 2003-09-11 | Midha Kamal K. | Method for preventing abuse of methylphenidate |
| US6340476B1 (en) * | 1999-04-06 | 2002-01-22 | Armaquest, Inc. | Pharmaceutical dosage form for pulsatile delivery of methylphenidate |
| US6221883B1 (en) * | 2000-04-12 | 2001-04-24 | Ross Baldessarini | Method of dopamine inhibition using l-threo-methylphenidate |
| US20020132793A1 (en) * | 2000-08-28 | 2002-09-19 | Mel Epstein | Use of methylphenidate compounds to enhance memory |
| US20020103162A1 (en) * | 2000-08-28 | 2002-08-01 | Mel Epstein | Use of threo-methylphenidate compounds to enhance memory |
| US6344215B1 (en) * | 2000-10-27 | 2002-02-05 | Eurand America, Inc. | Methylphenidate modified release formulations |
| US6359139B1 (en) * | 2000-11-07 | 2002-03-19 | Celgene Corporation | Methods for production of piperidyl acetamide stereoisomers |
| CA2499601A1 (en) * | 2002-09-19 | 2004-04-01 | University Of Utah Research Foundation | Modulating vesicular monoamine transporter trafficking and function: a novel approach for the treatment of parkinson's disease |
-
2005
- 2005-12-08 JP JP2007545674A patent/JP2008523097A/ja active Pending
- 2005-12-08 US US11/298,093 patent/US20060127421A1/en not_active Abandoned
- 2005-12-08 EP EP05853561A patent/EP1830648A4/en not_active Withdrawn
- 2005-12-08 WO PCT/US2005/044677 patent/WO2006063256A2/en active Application Filing
- 2005-12-08 CA CA002591247A patent/CA2591247A1/en not_active Abandoned
- 2005-12-08 NZ NZ555842A patent/NZ555842A/en not_active IP Right Cessation
- 2005-12-08 AU AU2005313887A patent/AU2005313887B2/en not_active Ceased
- 2005-12-08 BR BRPI0517166-0A patent/BRPI0517166A/pt not_active IP Right Cessation
- 2005-12-08 CN CNA2005800425053A patent/CN101076248A/zh active Pending
- 2005-12-08 KR KR1020077015592A patent/KR20070087643A/ko not_active Ceased
- 2005-12-09 AR ARP050105159A patent/AR053655A1/es unknown
-
2007
- 2007-06-07 IL IL183746A patent/IL183746A0/en unknown
- 2007-07-06 ZA ZA200705560A patent/ZA200705560B/xx unknown
-
2011
- 2011-01-12 US US13/005,068 patent/US20110118310A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106959367A (zh) * | 2009-10-30 | 2017-07-18 | 协和梅迪克斯株式会社 | 用于测定样本中的待测定成分的方法和试剂盒 |
| CN106959367B (zh) * | 2009-10-30 | 2019-06-14 | 协和梅迪克斯株式会社 | 用于测定样本中的待测定成分的方法和试剂盒 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL183746A0 (en) | 2007-10-31 |
| EP1830648A2 (en) | 2007-09-12 |
| NZ555842A (en) | 2010-10-29 |
| CA2591247A1 (en) | 2006-06-15 |
| US20110118310A1 (en) | 2011-05-19 |
| WO2006063256A2 (en) | 2006-06-15 |
| WO2006063256A3 (en) | 2007-03-29 |
| BRPI0517166A (pt) | 2008-09-30 |
| KR20070087643A (ko) | 2007-08-28 |
| AR053655A1 (es) | 2007-05-16 |
| JP2008523097A (ja) | 2008-07-03 |
| EP1830648A4 (en) | 2008-03-12 |
| ZA200705560B (en) | 2008-11-26 |
| US20060127421A1 (en) | 2006-06-15 |
| AU2005313887A1 (en) | 2006-06-15 |
| AU2005313887B2 (en) | 2011-10-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100093797A1 (en) | Methods For Treatment Of Cognitive And Menopausal Disorders With D-Threo Methylphenidate | |
| CA2678806C (en) | Treating adhd and other diseases involving inflammation | |
| JPH0637395B2 (ja) | ジペプタイド誘導体を含有する、筋萎縮性側索硬化症を治療するための薬剤 | |
| US20110118310A1 (en) | Treatment Using D-Threo Methylphenidate | |
| UA57733C2 (uk) | Спосіб профілактики відсроченого блювання та назальний аерозольний препарат метоклопраміду | |
| JP7695724B2 (ja) | 医薬組成物およびその適用 | |
| JP4614638B2 (ja) | 鎮痛剤組成物 | |
| US11478463B2 (en) | Mast cell stabilizers for treatment of chronic inflammatory conditions | |
| PT1492539E (pt) | Terapia de estatina para intensificar a manutenção cognitiva | |
| CN112656936A (zh) | 免疫细胞因子白介素-22在制备抗抑郁药物中的应用 | |
| CN115813932A (zh) | 一种用于重度抑郁症治疗的新的药物组合 | |
| CN1929841A (zh) | (+)－赤型－甲氟喹的药物组合物及其用途 | |
| JP4695326B2 (ja) | 鼻炎用医薬組成物 | |
| JP2008285474A (ja) | 抗アデノウイルス剤を含有する医薬組成物 | |
| Nicholas et al. | 5. Pharmacologic management | |
| JP2000212091A (ja) | 消化管機能異常治療剤 | |
| WO2000028984A1 (fr) | Remedes agissant contre un trouble fonctionnel du tractus digestif | |
| MXPA06012348A (es) | Metodos para atenuar el potencial de co-abuso. | |
| MXPA01006136A (en) | Combination of cerivastatin and fibrates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20071121 |