ES2752021T3 - Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades - Google Patents
Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades Download PDFInfo
- Publication number
- ES2752021T3 ES2752021T3 ES14712798T ES14712798T ES2752021T3 ES 2752021 T3 ES2752021 T3 ES 2752021T3 ES 14712798 T ES14712798 T ES 14712798T ES 14712798 T ES14712798 T ES 14712798T ES 2752021 T3 ES2752021 T3 ES 2752021T3
- Authority
- ES
- Spain
- Prior art keywords
- sulfasalazine
- pharmaceutical composition
- approximately
- methods
- patient
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 315
- 239000000203 mixture Substances 0.000 title claims description 176
- 208000015122 neurodegenerative disease Diseases 0.000 title claims description 85
- 230000004770 neurodegeneration Effects 0.000 title claims description 57
- 238000011282 treatment Methods 0.000 title description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 55
- 201000010099 disease Diseases 0.000 title description 49
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims abstract description 835
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims abstract description 825
- 229960001940 sulfasalazine Drugs 0.000 claims abstract description 824
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims abstract description 823
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 402
- 229920000642 polymer Polymers 0.000 claims abstract description 98
- 229920003083 Kollidon® VA64 Polymers 0.000 claims abstract description 82
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 38
- 206010053395 Progressive multiple sclerosis Diseases 0.000 claims description 73
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 63
- 238000010922 spray-dried dispersion Methods 0.000 claims description 39
- 206010015037 epilepsy Diseases 0.000 claims description 11
- 238000000338 in vitro Methods 0.000 description 192
- 241000699670 Mus sp. Species 0.000 description 92
- 230000036470 plasma concentration Effects 0.000 description 91
- 241000700159 Rattus Species 0.000 description 75
- 239000003937 drug carrier Substances 0.000 description 72
- 238000009472 formulation Methods 0.000 description 58
- 238000004458 analytical method Methods 0.000 description 56
- 210000000278 spinal cord Anatomy 0.000 description 50
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 49
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 49
- 208000004296 neuralgia Diseases 0.000 description 49
- 208000021722 neuropathic pain Diseases 0.000 description 49
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 43
- 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 description 40
- 239000007921 spray Substances 0.000 description 33
- 239000006186 oral dosage form Substances 0.000 description 31
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 30
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 29
- -1 2-pyridylsulfamoyl Chemical group 0.000 description 28
- 208000012902 Nervous system disease Diseases 0.000 description 27
- 208000025966 Neurological disease Diseases 0.000 description 27
- 239000006185 dispersion Substances 0.000 description 27
- 239000003814 drug Substances 0.000 description 27
- 102100035300 Cystine/glutamate transporter Human genes 0.000 description 26
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 26
- 108091006241 SLC7A11 Proteins 0.000 description 26
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 26
- 210000002381 plasma Anatomy 0.000 description 26
- 230000004083 survival effect Effects 0.000 description 24
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 22
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 22
- 210000004705 lumbosacral region Anatomy 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 19
- 210000001130 astrocyte Anatomy 0.000 description 19
- 229930195712 glutamate Natural products 0.000 description 19
- 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 description 19
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 19
- 206010039073 rheumatoid arthritis Diseases 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 18
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 17
- 230000004913 activation Effects 0.000 description 17
- 229920002678 cellulose Chemical class 0.000 description 17
- 239000001913 cellulose Chemical class 0.000 description 17
- 235000010980 cellulose Nutrition 0.000 description 17
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 229920001577 copolymer Polymers 0.000 description 15
- 230000000926 neurological effect Effects 0.000 description 14
- 229960004181 riluzole Drugs 0.000 description 14
- 208000024827 Alzheimer disease Diseases 0.000 description 13
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 201000006417 multiple sclerosis Diseases 0.000 description 13
- 229960002806 daclizumab Drugs 0.000 description 12
- 229920001519 homopolymer Polymers 0.000 description 12
- 230000003959 neuroinflammation Effects 0.000 description 12
- 230000002314 neuroinflammatory effect Effects 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 210000001056 activated astrocyte Anatomy 0.000 description 11
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 11
- 229960000556 fingolimod Drugs 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 208000023105 Huntington disease Diseases 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 208000018737 Parkinson disease Diseases 0.000 description 10
- 208000030886 Traumatic Brain injury Diseases 0.000 description 10
- 210000004960 anterior grey column Anatomy 0.000 description 10
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 10
- 238000000634 powder X-ray diffraction Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000009529 traumatic brain injury Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 210000001642 activated microglia Anatomy 0.000 description 9
- 210000003169 central nervous system Anatomy 0.000 description 9
- 229960000913 crospovidone Drugs 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 9
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 9
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 9
- 238000011002 quantification Methods 0.000 description 9
- 208000032382 Ischaemic stroke Diseases 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000006724 microglial activation Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000001694 spray drying Methods 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 7
- 206010012289 Dementia Diseases 0.000 description 7
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 7
- 206010013886 Dysaesthesia Diseases 0.000 description 7
- 201000011240 Frontotemporal dementia Diseases 0.000 description 7
- 208000004454 Hyperalgesia Diseases 0.000 description 7
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 208000006289 Rett Syndrome Diseases 0.000 description 7
- 206010053552 allodynia Diseases 0.000 description 7
- 229940064856 azulfidine Drugs 0.000 description 7
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000001565 modulated differential scanning calorimetry Methods 0.000 description 7
- 208000035824 paresthesia Diseases 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- KIHYPELVXPAIDH-HNSNBQBZSA-N 1-[[4-[(e)-n-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-c-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid Chemical compound CCC1=CC(C(\C)=N\OCC=2C=C(C(C3CCCCC3)=CC=2)C(F)(F)F)=CC=C1CN1CC(C(O)=O)C1 KIHYPELVXPAIDH-HNSNBQBZSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 6
- 206010061818 Disease progression Diseases 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002139 L01XE22 - Masitinib Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 6
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
- 230000001910 anti-glutamatergic effect Effects 0.000 description 6
- 229940112129 campath Drugs 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229960002436 cladribine Drugs 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 6
- 230000005750 disease progression Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 230000009206 glutamatergic signaling Effects 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 229960004577 laquinimod Drugs 0.000 description 6
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 description 6
- 229940047834 lemtrada Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- WJEOLQLKVOPQFV-UHFFFAOYSA-N masitinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3SC=C(N=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 WJEOLQLKVOPQFV-UHFFFAOYSA-N 0.000 description 6
- 229960004655 masitinib Drugs 0.000 description 6
- 229960001156 mitoxantrone Drugs 0.000 description 6
- 210000002161 motor neuron Anatomy 0.000 description 6
- 229950005751 ocrelizumab Drugs 0.000 description 6
- 230000000750 progressive effect Effects 0.000 description 6
- 229960004641 rituximab Drugs 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 229950005693 siponimod Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229940121136 tecfidera Drugs 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 208000009999 tuberous sclerosis Diseases 0.000 description 6
- 229940079023 tysabri Drugs 0.000 description 6
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- HLKZFSVWBQSKKH-UHFFFAOYSA-N but-3-enoic acid;1-ethenylpyrrolidin-2-one Chemical compound OC(=O)CC=C.C=CN1CCCC1=O HLKZFSVWBQSKKH-UHFFFAOYSA-N 0.000 description 5
- 208000037765 diseases and disorders Diseases 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- 210000004498 neuroglial cell Anatomy 0.000 description 5
- 239000008196 pharmacological composition Substances 0.000 description 5
- 229920001983 poloxamer Polymers 0.000 description 5
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 5
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- GECHUMIMRBOMGK-UHFFFAOYSA-N sulfapyridine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=CC=N1 GECHUMIMRBOMGK-UHFFFAOYSA-N 0.000 description 5
- 229960002211 sulfapyridine Drugs 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 210000000115 thoracic cavity Anatomy 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 4
- 229920003091 Methocel™ Polymers 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 210000003050 axon Anatomy 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229960001680 ibuprofen Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- FDFKDQNRMVBBTQ-UHFFFAOYSA-N C(C=1C(C(=O)O)=CC=CC1)(=O)O.OCCCOC(C)=O Chemical compound C(C=1C(C(=O)O)=CC=CC1)(=O)O.OCCCOC(C)=O FDFKDQNRMVBBTQ-UHFFFAOYSA-N 0.000 description 3
- 108010029697 CD40 Ligand Proteins 0.000 description 3
- 102100032937 CD40 ligand Human genes 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 229920003134 Eudragit® polymer Polymers 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 206010028289 Muscle atrophy Diseases 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical class CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003593 chromogenic compound Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002178 crystalline material Substances 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 229960003943 hypromellose Drugs 0.000 description 3
- 235000015110 jellies Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- KBOPZPXVLCULAV-UHFFFAOYSA-M mesalaminate(1-) Chemical compound NC1=CC=C(O)C(C([O-])=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-M 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- 210000000274 microglia Anatomy 0.000 description 3
- 230000002025 microglial effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000020763 muscle atrophy Effects 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 235000019615 sensations Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- VTMJKPGFERYGJF-ZETCQYMHSA-N 4-[(s)-amino(carboxy)methyl]benzoic acid Chemical group OC(=O)[C@@H](N)C1=CC=C(C(O)=O)C=C1 VTMJKPGFERYGJF-ZETCQYMHSA-N 0.000 description 2
- YNLYSYYYCDVVJF-UHFFFAOYSA-N 4-[N-[3,5-bis(trifluoromethyl)anilino]-C-methylcarbonimidoyl]-5-[[4-(trifluoromethyl)phenyl]methyl]-1,2-oxazole-3-carboxylic acid Chemical compound C=1C=C(C(F)(F)F)C=CC=1CC=1ON=C(C(O)=O)C=1C(C)=NNC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 YNLYSYYYCDVVJF-UHFFFAOYSA-N 0.000 description 2
- 208000011403 Alexander disease Diseases 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000004044 Hypesthesia Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- OYIFNHCXNCRBQI-BYPYZUCNSA-N L-2-aminoadipic acid Chemical compound OC(=O)[C@@H](N)CCCC(O)=O OYIFNHCXNCRBQI-BYPYZUCNSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000037273 Pathologic Processes Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010059712 Pronase Proteins 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000906446 Theraps Species 0.000 description 2
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 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 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- QIHLUZAFSSMXHQ-UHFFFAOYSA-N budipine Chemical compound C1CN(C(C)(C)C)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QIHLUZAFSSMXHQ-UHFFFAOYSA-N 0.000 description 2
- 229960002452 budipine Drugs 0.000 description 2
- 239000000337 buffer salt Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003596 drug target Substances 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000003492 excitotoxic effect Effects 0.000 description 2
- 231100000063 excitotoxicity Toxicity 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000009477 glass transition Effects 0.000 description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 208000034783 hypoesthesia Diseases 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 229940062717 keppra Drugs 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 229940072170 lamictal Drugs 0.000 description 2
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 2
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical compound CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- 230000006764 neuronal dysfunction Effects 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000009054 pathological process Effects 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 230000002974 pharmacogenomic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 2
- 229960001233 pregabalin Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000001739 rebound effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000007962 solid dispersion Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940035305 topamax Drugs 0.000 description 2
- 125000005591 trimellitate group Chemical group 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 1
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- JJNQWYPLIWCKRB-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]ethynyl]benzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 JJNQWYPLIWCKRB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DOUBAFNWVFAWEC-UHFFFAOYSA-N 3-hydroxypropyl acetate Chemical compound CC(=O)OCCCO DOUBAFNWVFAWEC-UHFFFAOYSA-N 0.000 description 1
- JBGQWKQSSOCCDO-UHFFFAOYSA-N 5-benzyl-4-[N-[3,5-bis(trifluoromethyl)anilino]-C-methylcarbonimidoyl]-1,2-oxazole-3-carboxylic acid Chemical compound C=1C=CC=CC=1CC=1ON=C(C(O)=O)C=1C(C)=NNC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JBGQWKQSSOCCDO-UHFFFAOYSA-N 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102000006941 Amino Acid Transport System X-AG Human genes 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 208000003164 Diplopia Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 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 description 1
- 108091006151 Glutamate transporters Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 101000884399 Homo sapiens Arylamine N-acetyltransferase 2 Proteins 0.000 description 1
- 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 description 1
- 101000693844 Homo sapiens Insulin-like growth factor-binding protein complex acid labile subunit Proteins 0.000 description 1
- 101000635799 Homo sapiens Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Proteins 0.000 description 1
- 101100149812 Homo sapiens SOD1 gene Proteins 0.000 description 1
- 101000713305 Homo sapiens Sodium-coupled neutral amino acid transporter 1 Proteins 0.000 description 1
- 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
- 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229920005479 Lucite® Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 1
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 1
- 229920003108 Methocel™ A4M Polymers 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100113998 Mus musculus Cnbd2 gene Proteins 0.000 description 1
- 101000693855 Mus musculus Insulin-like growth factor-binding protein complex acid labile subunit Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 102100026783 N-alpha-acetyltransferase 16, NatA auxiliary subunit Human genes 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010034962 Photopsia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102100030852 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Human genes 0.000 description 1
- 238000011831 SOD1-G93A transgenic mouse Methods 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000006463 Talin Human genes 0.000 description 1
- 108010083809 Talin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 238000001772 Wald test Methods 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000007844 axonal damage Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000022371 chronic pain syndrome Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 229920001531 copovidone Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940057307 dihydrate calcium sulfate Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000004914 glial activation Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000001057 ionotropic effect Effects 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910000065 phosphene Inorganic materials 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229940072169 rilutek Drugs 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 101150062190 sod1 gene Proteins 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 230000003238 somatosensory effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 229940034107 sulfazine Drugs 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011222 transcriptome analysis Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361759933P | 2013-02-01 | 2013-02-01 | |
| US201361780340P | 2013-03-13 | 2013-03-13 | |
| PCT/US2014/014290 WO2014121137A2 (en) | 2013-02-01 | 2014-01-31 | Compositions and methods for the treatment of neurodegenerative and other diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2752021T3 true ES2752021T3 (es) | 2020-04-02 |
Family
ID=50382538
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14712798T Active ES2752021T3 (es) | 2013-02-01 | 2014-01-31 | Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US9597339B2 (OSRAM) |
| EP (1) | EP2950797B1 (OSRAM) |
| JP (2) | JP6328146B2 (OSRAM) |
| KR (1) | KR20150139830A (OSRAM) |
| CN (1) | CN105163735B (OSRAM) |
| AU (2) | AU2014212109B2 (OSRAM) |
| CA (1) | CA2899032A1 (OSRAM) |
| ES (1) | ES2752021T3 (OSRAM) |
| IL (1) | IL240206A0 (OSRAM) |
| WO (1) | WO2014121137A2 (OSRAM) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2752021T3 (es) * | 2013-02-01 | 2020-04-02 | Glialogix Inc | Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades |
| KR102364840B1 (ko) * | 2014-11-05 | 2022-02-18 | 삼성전자주식회사 | 신경세포의 탈수초화와 연관된 질환을 치료하기 위한 약학적 조성물 및 그를 이용하는 방법 |
| US20160199393A1 (en) * | 2015-01-08 | 2016-07-14 | China Medical University | Methods of treating brain ischemia or hypoxia |
| ES2650175B1 (es) * | 2016-04-15 | 2019-02-04 | Servicio Andaluz De Salud | Tratamiento de enfermedades neurodegenerativas |
| CN109414507A (zh) * | 2016-04-26 | 2019-03-01 | 美国圣路易斯大学 | 用于预防和治疗神经退行性疾病的高度选择性腺苷a3受体亚型激动剂 |
| US20180110760A1 (en) * | 2016-10-21 | 2018-04-26 | Glialogix, Inc. | Compositions and methods for the treatmentof neurodegenerative and other diseases |
| US10473672B2 (en) * | 2017-02-09 | 2019-11-12 | Kaohsiung Chang Gung Memorial Hospital | Methods for diagnosing and treating Alzheimers disease using G72 protein and SLC7A11 mRNA as biomarkers |
| RU2680844C1 (ru) * | 2017-10-12 | 2019-02-28 | федеральное государственное автономное образовательное учреждение высшего образования "Казанский (Приволжский) федеральный университет" (ФГАОУ ВО КФУ) | Применение сульфасалазина в качестве ингибитора образования конечных продуктов гликирования |
| WO2019102992A1 (ja) * | 2017-11-21 | 2019-05-31 | 積水化学工業株式会社 | 皮膚外用剤 |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2396145A (en) | 1940-12-14 | 1946-03-05 | Pharmscia Ab | Heterocyclic sulphonamido azo compounds |
| FR2608988B1 (fr) | 1986-12-31 | 1991-01-11 | Centre Nat Rech Scient | Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanoparticules |
| MX9702357A (es) | 1994-09-29 | 1997-06-28 | Andaris Ltd | Microparticulas secadas por aspersion como vehiculos terapeuticos. |
| US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| ITMI962356A1 (it) | 1996-11-13 | 1998-05-13 | Uni Degli Studi Di Brescia D I | Uso di composti derivati da molecole ad attivita' antinfiammatoria di tipo non steroideo per la prevenzione e il trattamento di |
| PT954282E (pt) | 1997-01-16 | 2005-06-30 | Massachusetts Inst Technology | Preparacao de particulas para inalacao |
| WO1999066903A2 (en) | 1998-06-24 | 1999-12-29 | Advanced Inhalation Research, Inc. | Large porous particles emitted from an inhaler |
| DE69936386T2 (de) | 1998-08-25 | 2008-03-06 | Advanced Inhalation Research, Inc., Cambridge | Sprühgetrocknete proteinformulierungen |
| US6586008B1 (en) | 1999-08-25 | 2003-07-01 | Advanced Inhalation Research, Inc. | Use of simple amino acids to form porous particles during spray drying |
| KR100417623B1 (ko) | 2000-03-28 | 2004-02-05 | 주식회사 뉴로테크 | 뇌질환 예방 및 치료용 조성물 |
| CA2307278A1 (en) | 2000-04-28 | 2001-10-28 | University Of British Columbia | Use of n-heterocyclic substituted salicylic acids for inhibition of cellular uptake of cystine |
| KR100664822B1 (ko) | 2002-02-01 | 2007-01-04 | 화이자 프로덕츠 인코포레이티드 | 변형된 분무-건조 장치를 이용한 균질한 분무-건조된 고체비결정성 약물 분산액의 제조 방법 |
| AU2003239463B2 (en) | 2002-02-01 | 2007-10-18 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions using pressure nozzles |
| CL2004001884A1 (es) | 2003-08-04 | 2005-06-03 | Pfizer Prod Inc | Procedimiento de secado por pulverizacion para la formacion de dispersiones solidas amorfas de un farmaco y polimeros. |
| US20060045865A1 (en) | 2004-08-27 | 2006-03-02 | Spherics, Inc. | Controlled regional oral delivery |
| EP1824564A4 (en) | 2004-10-27 | 2009-09-16 | Uab Research Foundation | METHOD FOR TREATING GLIOM |
| CA2620389C (en) | 2005-08-31 | 2014-06-17 | Abraxis Bioscience, Llc | Compositions and methods for preparation of poorly water soluble drugs with increased stability |
| US20070053869A1 (en) | 2005-09-02 | 2007-03-08 | Yuichi Sugiyama | Formulation and method for enhancement of gastrointestinal absorption of pharmaceutical agents |
| GB0602123D0 (en) * | 2006-02-02 | 2006-03-15 | Novartis Ag | Organic compounds |
| ES2672627T3 (es) | 2006-02-02 | 2018-06-15 | Novartis Ag | Tratamiento de la esclerosis tuberosa |
| US7964585B2 (en) | 2006-03-14 | 2011-06-21 | Case Western Reserve University | Composition and method of treating peripheral neuropathy |
| NZ575171A (en) | 2006-08-31 | 2012-04-27 | Aptalis Pharmatech Inc | Drug delivery systems comprising solid solutions of weakly basic drugs |
| WO2008135828A2 (en) | 2007-05-03 | 2008-11-13 | Pfizer Products Inc. | Nanoparticles comprising a drug, ethylcellulose, and a bile salt |
| WO2009073215A1 (en) | 2007-12-06 | 2009-06-11 | Bend Research, Inc. | Pharmaceutical compositions comprising nanoparticles and a resuspending material |
| CN101959504A (zh) * | 2008-02-28 | 2011-01-26 | 比艾尔-坡特拉有限公司 | 用于难溶性药物的药物组合物 |
| PT2113254E (pt) * | 2008-04-28 | 2012-11-26 | Txcell | Composições para o tratamento de um estado inflamatório auto-imune |
| TW201014605A (en) | 2008-09-16 | 2010-04-16 | Genentech Inc | Methods for treating progressive multiple sclerosis |
| EP3130396B1 (en) | 2009-03-27 | 2021-03-17 | Bend Research, Inc. | Spray-drying process |
| WO2012031129A2 (en) | 2010-09-03 | 2012-03-08 | Bend Research, Inc. | Spray-drying apparatus and methods of using the same |
| US9084944B2 (en) | 2010-09-03 | 2015-07-21 | Bend Research, Inc. | Spray-drying apparatus and methods of using the same |
| HK1204970A1 (en) | 2012-01-31 | 2015-12-11 | Cerulean Pharma Inc. | Polymer-agent conjugates, particles, compositions, and related methods of use |
| ES2752021T3 (es) * | 2013-02-01 | 2020-04-02 | Glialogix Inc | Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades |
| WO2015103230A1 (en) | 2013-12-31 | 2015-07-09 | Ascendia Pharmaceuticals, Llc | Pharmaceutical compositions for poorly water-soluble compounds |
-
2014
- 2014-01-31 ES ES14712798T patent/ES2752021T3/es active Active
- 2014-01-31 US US14/170,405 patent/US9597339B2/en not_active Expired - Fee Related
- 2014-01-31 JP JP2015556185A patent/JP6328146B2/ja not_active Expired - Fee Related
- 2014-01-31 CA CA2899032A patent/CA2899032A1/en not_active Abandoned
- 2014-01-31 WO PCT/US2014/014290 patent/WO2014121137A2/en not_active Ceased
- 2014-01-31 CN CN201480019892.8A patent/CN105163735B/zh not_active Expired - Fee Related
- 2014-01-31 AU AU2014212109A patent/AU2014212109B2/en not_active Ceased
- 2014-01-31 KR KR1020157023718A patent/KR20150139830A/ko not_active Withdrawn
- 2014-01-31 EP EP14712798.9A patent/EP2950797B1/en active Active
-
2015
- 2015-07-29 IL IL240206A patent/IL240206A0/en unknown
-
2016
- 2016-11-30 US US15/365,843 patent/US9980978B2/en not_active Expired - Fee Related
- 2016-11-30 US US15/365,835 patent/US9974798B2/en not_active Expired - Fee Related
-
2017
- 2017-02-10 US US15/430,294 patent/US9918997B2/en not_active Expired - Fee Related
-
2018
- 2018-04-17 US US15/955,020 patent/US10398713B2/en not_active Expired - Fee Related
- 2018-04-17 JP JP2018079284A patent/JP2018123159A/ja active Pending
- 2018-08-28 AU AU2018222921A patent/AU2018222921A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014121137A3 (en) | 2014-11-27 |
| KR20150139830A (ko) | 2015-12-14 |
| WO2014121137A2 (en) | 2014-08-07 |
| EP2950797B1 (en) | 2019-09-11 |
| JP2016507526A (ja) | 2016-03-10 |
| AU2014212109A1 (en) | 2015-08-06 |
| CN105163735B (zh) | 2018-12-11 |
| JP2018123159A (ja) | 2018-08-09 |
| US20170079991A1 (en) | 2017-03-23 |
| US9974798B2 (en) | 2018-05-22 |
| US20140221321A1 (en) | 2014-08-07 |
| US9597339B2 (en) | 2017-03-21 |
| US9980978B2 (en) | 2018-05-29 |
| US20170165279A1 (en) | 2017-06-15 |
| AU2014212109B2 (en) | 2018-05-31 |
| US20190015431A1 (en) | 2019-01-17 |
| JP6328146B2 (ja) | 2018-05-23 |
| CA2899032A1 (en) | 2014-08-07 |
| CN105163735A (zh) | 2015-12-16 |
| US20170079990A1 (en) | 2017-03-23 |
| AU2018222921A1 (en) | 2018-09-20 |
| US10398713B2 (en) | 2019-09-03 |
| EP2950797A2 (en) | 2015-12-09 |
| IL240206A0 (en) | 2015-09-24 |
| US9918997B2 (en) | 2018-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2752021T3 (es) | Composiciones y métodos para el tratamiento de enfermedades neurodegenerativas y otras enfermedades | |
| ES2320847T3 (es) | Formulaciones mejoradas de lamotrigina | |
| HK1248521A1 (en) | Oral therapeutic compound delivery system | |
| Aslani et al. | Design, formulation and evaluation of its physiochemical properties of acetaminophen, ibuprofen and caffeine as effervescent tablet | |
| KR102486126B1 (ko) | 알펠리십을 포함하는 제약 조성물 | |
| JP2022160654A (ja) | 細胞生存性及び／又は細胞増殖を低減するための薬物の組み合わせ | |
| US20200009118A1 (en) | Compositions and methods for the treatmentof neurodegenerative and other diseases | |
| ES2729208T3 (es) | Terapia basada en baclofeno y acamprosato de trastornos de degeneración macular | |
| ES2963626T3 (es) | Una composición farmacéutica de un compuesto de pirazol dispersado en una matriz polimérica | |
| Deshmukh et al. | Probiotic-assisted colon-specific delivery of anti-inflammatory Drug-5 ASA | |
| KR20250152109A (ko) | 종양학적 병리 및 신경병증성 통증 치료에 사용하기 위한 2-하이드록시-옥타데센-9-시스-오에이트 | |
| Ochiuz et al. | Hydrophilic Matrix Tablets Based on Carbopol for Improving the Oral Bioavailability of Sodium |