DK2364084T3 - Farmaceutiske sammensætninger med lavdosis liponsyre og fremgangsmåder - Google Patents
Farmaceutiske sammensætninger med lavdosis liponsyre og fremgangsmåder Download PDFInfo
- Publication number
- DK2364084T3 DK2364084T3 DK09825441.0T DK09825441T DK2364084T3 DK 2364084 T3 DK2364084 T3 DK 2364084T3 DK 09825441 T DK09825441 T DK 09825441T DK 2364084 T3 DK2364084 T3 DK 2364084T3
- Authority
- DK
- Denmark
- Prior art keywords
- lens
- pharmaceutical composition
- lipoic acid
- age
- cells
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 24
- 235000019136 lipoic acid Nutrition 0.000 title description 28
- 229960002663 thioctic acid Drugs 0.000 title description 28
- 238000000034 method Methods 0.000 title description 27
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 title 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 44
- 239000013543 active substance Substances 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 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 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 claims 1
- 210000000695 crystalline len Anatomy 0.000 description 66
- 239000003795 chemical substances by application Substances 0.000 description 26
- 230000002350 accommodative effect Effects 0.000 description 19
- 230000007423 decrease Effects 0.000 description 16
- 208000002177 Cataract Diseases 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 206010024214 Lenticular opacities Diseases 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- IZFHEQBZOYJLPK-SSDOTTSWSA-N (R)-dihydrolipoic acid Chemical compound OC(=O)CCCC[C@@H](S)CCS IZFHEQBZOYJLPK-SSDOTTSWSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 201000010041 presbyopia Diseases 0.000 description 6
- IZFHEQBZOYJLPK-UHFFFAOYSA-N dihydrolipoic acid Chemical compound OC(=O)CCCCC(S)CCS IZFHEQBZOYJLPK-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- GZKOSYKBUIHLIZ-UHFFFAOYSA-N 5-(thiaselenolan-3-yl)pentanoic acid Chemical compound OC(=O)CCCCC1CCS[Se]1 GZKOSYKBUIHLIZ-UHFFFAOYSA-N 0.000 description 4
- PKMRODAPABWQIT-UHFFFAOYSA-N 5-(thiaselenolan-5-yl)pentanoic acid Chemical compound OC(=O)CCCCC1CC[Se]S1 PKMRODAPABWQIT-UHFFFAOYSA-N 0.000 description 4
- 230000004308 accommodation Effects 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000004792 oxidative damage Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 3
- 101000654530 Tupaia virus (isolate Tupaia/Thailand/-/1986) Small hydrophobic protein Proteins 0.000 description 3
- 238000006664 bond formation reaction Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 210000003644 lens cell Anatomy 0.000 description 3
- 210000001542 lens epithelial cell Anatomy 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 229910052711 selenium Inorganic materials 0.000 description 3
- 239000011669 selenium Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 231100000750 In vitro toxicology Toxicity 0.000 description 2
- 101710150593 Protein beta Proteins 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 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 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000007723 transport mechanism Effects 0.000 description 2
- AYDAHOIUHVUJHQ-UHFFFAOYSA-N 1-(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)pyrrole-2,5-dione Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=CC=2)OC(=O)C1=CC=2N1C(=O)C=CC1=O AYDAHOIUHVUJHQ-UHFFFAOYSA-N 0.000 description 1
- YGIABALXNBVHBX-UHFFFAOYSA-N 1-[4-[7-(diethylamino)-4-methyl-2-oxochromen-3-yl]phenyl]pyrrole-2,5-dione Chemical compound O=C1OC2=CC(N(CC)CC)=CC=C2C(C)=C1C(C=C1)=CC=C1N1C(=O)C=CC1=O YGIABALXNBVHBX-UHFFFAOYSA-N 0.000 description 1
- UHXDQFCGWCHHSL-UHFFFAOYSA-N 5-(diselenolan-3-yl)pentanoic acid Chemical group OC(=O)CCCCC1CC[Se][Se]1 UHXDQFCGWCHHSL-UHFFFAOYSA-N 0.000 description 1
- 102000003669 Antiporters Human genes 0.000 description 1
- 108090000084 Antiporters Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000013578 denaturing buffer Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000087 laser glass Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
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- 102000035118 modified proteins Human genes 0.000 description 1
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- 239000002637 mydriatic agent Substances 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 239000002071 nanotube Substances 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003342 selenium Chemical class 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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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
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- 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
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Claims (11)
1. Farmaceutisk sammensætning til okular anvendelse omfattende aktivstof som er: 5-(l,2-dithiolan-3-yl)pentansyre; 6,8-dimercaptooctanonsyre; dihydrolipoat; 5-(l,2-thiaselenolan-5-yl)penta nsyre, 5-(l,2-thiaselenolan-3-yl)penta nsyre; eller et salt eller ester deraf, i en mængde på 10 til 250 μΜ og mindst én farmaceutisk acceptabel bærer.
2. Farmaceutisk sammensætning til anvendelse ifølge krav 1, hvor aktivstoffet er til stede i en mængde på 10 til 100 μΜ.
3. Farmaceutisk sammensætning til anvendelse ifølge krav 1, hvor aktivstoffet er 5-(l,2-dithiolan-3-yl)pentansyre eller et salt eller ester deraf.
4. Farmaceutisk sammensætning til anvendelse ifølge krav 1, hvor aktivstoffet er R-enantiomeren.
5. Farmaceutisk sammensætning til anvendelse ifølge krav 1, omfattende en emulgator og en bufret bærer.
6. Farmaceutisk sammensætning ifølge kravene 1 til 5 til anvendelse i forebyggelse eller behandling af iltningsbeskadigelse af celler.
7. Farmaceutisk sammensætning til anvendelse ifølge krav 6, yderligere omfattende en kemisk energikilde til simultan eller fortløbende anvendelse med aktivstoffet.
8. Farmaceutisk sammensætning ifølge krav 7, hvor den aktive kemiske energikilde administreres simultant med aktivstoffet.
9. Farmaceutisk sammensætning til anvendelse ifølge krav 8, hvor den kemiske energikilde er glucose eller NADPH.
10. Farmaceutisk sammensætning ifølge krav 6, hvor behandlingen yderligere omfatter tilførsel af energi for at fremme brydning af disulfidbindinger.
11. Farmaceutisk sammensætning ifølge krav 6, hvor cellerne er okularceller.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/267,208 US9044439B2 (en) | 2008-03-05 | 2008-11-07 | Low dose lipoic and pharmaceutical compositions and methods |
| PCT/US2009/063469 WO2010054135A1 (en) | 2008-11-07 | 2009-11-06 | Low dose lipoic acid pharmaceutical compositions and methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2364084T3 true DK2364084T3 (da) | 2016-01-25 |
Family
ID=41054317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09825441.0T DK2364084T3 (da) | 2008-11-07 | 2009-11-06 | Farmaceutiske sammensætninger med lavdosis liponsyre og fremgangsmåder |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US9044439B2 (da) |
| EP (2) | EP2939539B1 (da) |
| CA (1) | CA2742973C (da) |
| DK (1) | DK2364084T3 (da) |
| ES (2) | ES2561600T3 (da) |
| PL (1) | PL2364084T3 (da) |
| WO (1) | WO2010054135A1 (da) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050112113A1 (en) * | 2000-08-16 | 2005-05-26 | Till Jonathan S. | Presbyopia treatment by lens alteration |
| US8697109B2 (en) | 2000-08-16 | 2014-04-15 | Encore Health, Llc | Caged mercaptan and seleno-mercaptan compounds and methods of using them |
| US7914815B2 (en) * | 2000-08-16 | 2011-03-29 | Encore Health, Llc | Method for delivery of pharmaceuticals for treating or preventing presbyopia |
| US8647612B2 (en) * | 2008-03-05 | 2014-02-11 | Encore Health, Llc | Dithiol compounds, derivatives, and treatment of presbyopia |
| US7935332B2 (en) * | 2000-08-16 | 2011-05-03 | Encore Health, Llc | Presbyopia treatment by lens alteration |
| US8147816B2 (en) * | 2000-08-16 | 2012-04-03 | Encore Health, Llc | Presbyopia treatment by lens alteration |
| US8102027B2 (en) * | 2007-08-21 | 2012-01-24 | Broadcom Corporation | IC package sacrificial structures for crack propagation confinement |
| WO2009111635A2 (en) | 2008-03-05 | 2009-09-11 | Encore Health, Llc | Dithiol compounds, derivatives, and uses therefor |
| US9044439B2 (en) | 2008-03-05 | 2015-06-02 | Encore Health, Llc | Low dose lipoic and pharmaceutical compositions and methods |
| EP4082542A1 (en) | 2009-06-15 | 2022-11-02 | Encore Health, LLC | Dithiol compounds, derivatives, and uses therefor |
| EP2442645B1 (en) | 2009-06-15 | 2014-08-27 | Encore Health, Llc | Choline esters |
| TWI588560B (zh) | 2012-04-05 | 2017-06-21 | 布萊恩荷登視覺協會 | 用於屈光不正之鏡片、裝置、方法及系統 |
| US9201250B2 (en) | 2012-10-17 | 2015-12-01 | Brien Holden Vision Institute | Lenses, devices, methods and systems for refractive error |
| JP2015533430A (ja) | 2012-10-17 | 2015-11-24 | ブリエン ホールデン ビジョン インスティテュートBrien Holden Vision Institute | 屈折異常用のレンズ、デバイス、方法、及びシステム |
| MX384877B (es) * | 2014-03-03 | 2025-03-14 | Novartis Ag | Composiciones de éster de colina de ácido lipoico y métodos de uso. |
| TW202103696A (zh) * | 2019-04-17 | 2021-02-01 | 日商參天製藥股份有限公司 | 硫辛酸前藥 |
| CN113387923A (zh) | 2020-03-13 | 2021-09-14 | 诺华股份有限公司 | 硫辛酸胆碱酯盐的药物组合物及使用其的治疗方法 |
Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB935962A (en) | 1960-06-17 | 1963-09-04 | Fujisawa Pharmaceutical Co | Improvements in or relating to the production of 6.8-dithiooctanamides |
| US3855240A (en) | 1969-04-28 | 1974-12-17 | Exxon Research Engineering Co | Sulfur containing heterocycles |
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2008
- 2008-11-07 US US12/267,208 patent/US9044439B2/en active Active
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- 2009-11-06 EP EP15162722.1A patent/EP2939539B1/en not_active Not-in-force
- 2009-11-06 PL PL09825441T patent/PL2364084T3/pl unknown
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| US20090227677A1 (en) | 2009-09-10 |
| EP2364084A1 (en) | 2011-09-14 |
| US20150297561A1 (en) | 2015-10-22 |
| EP2364084A4 (en) | 2012-05-23 |
| US9517225B2 (en) | 2016-12-13 |
| PL2364084T3 (pl) | 2016-06-30 |
| CA2742973C (en) | 2017-05-23 |
| HK1212157A1 (en) | 2016-06-10 |
| EP2939539A1 (en) | 2015-11-04 |
| ES2681477T3 (es) | 2018-09-13 |
| US9044439B2 (en) | 2015-06-02 |
| CA2742973A1 (en) | 2010-05-14 |
| EP2364084B1 (en) | 2016-01-06 |
| WO2010054135A1 (en) | 2010-05-14 |
| ES2561600T3 (es) | 2016-02-29 |
| EP2939539B1 (en) | 2018-04-25 |
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