CA3046355C - Glyceryl 3-hydroxybutyrates for traumatic brain injury - Google Patents
Glyceryl 3-hydroxybutyrates for traumatic brain injury Download PDFInfo
- Publication number
- CA3046355C CA3046355C CA3046355A CA3046355A CA3046355C CA 3046355 C CA3046355 C CA 3046355C CA 3046355 A CA3046355 A CA 3046355A CA 3046355 A CA3046355 A CA 3046355A CA 3046355 C CA3046355 C CA 3046355C
- Authority
- CA
- Canada
- Prior art keywords
- hydroxybutyrate
- glyceryl
- composition
- ester
- tbi
- 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
- 208000030886 Traumatic Brain injury Diseases 0.000 title claims abstract description 88
- 230000009529 traumatic brain injury Effects 0.000 title claims abstract description 88
- CBTHKODKAPVTNY-UHFFFAOYSA-N 2,3-dihydroxypropyl 3-hydroxybutanoate Chemical class CC(O)CC(=O)OCC(O)CO CBTHKODKAPVTNY-UHFFFAOYSA-N 0.000 title 1
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 230000000149 penetrating effect Effects 0.000 claims abstract description 9
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical group CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 56
- -1 glyceryl (3-hydroxybutyrate) ester Chemical class 0.000 claims description 54
- WHBMMWSBFZVSSR-UHFFFAOYSA-M 3-hydroxybutyrate Chemical compound CC(O)CC([O-])=O WHBMMWSBFZVSSR-UHFFFAOYSA-M 0.000 claims description 51
- 150000002148 esters Chemical class 0.000 claims description 45
- 150000002576 ketones Chemical class 0.000 claims description 45
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 42
- 208000027418 Wounds and injury Diseases 0.000 claims description 35
- 208000014674 injury Diseases 0.000 claims description 35
- 230000006378 damage Effects 0.000 claims description 34
- 239000007983 Tris buffer Substances 0.000 claims description 31
- 235000005911 diet Nutrition 0.000 claims description 27
- 230000037213 diet Effects 0.000 claims description 27
- 230000037058 blood plasma level Effects 0.000 claims description 24
- 208000024891 symptom Diseases 0.000 claims description 20
- 230000037406 food intake Effects 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 15
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 claims description 12
- 201000001421 hyperglycemia Diseases 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- 230000037396 body weight Effects 0.000 claims description 11
- 150000001720 carbohydrates Chemical class 0.000 claims description 11
- 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 10
- 239000008103 glucose Substances 0.000 claims description 10
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 claims description 9
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical group CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 claims description 6
- 230000000926 neurological effect Effects 0.000 claims description 4
- 230000002411 adverse Effects 0.000 claims description 3
- 230000036765 blood level Effects 0.000 claims description 3
- 208000029028 brain injury Diseases 0.000 claims description 3
- 230000002085 persistent effect Effects 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 2
- 235000021590 normal diet Nutrition 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 230000001052 transient effect Effects 0.000 claims description 2
- 238000011477 surgical intervention Methods 0.000 claims 10
- 210000004958 brain cell Anatomy 0.000 claims 4
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical group CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 claims 3
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 125000005456 glyceride group Chemical group 0.000 abstract description 2
- 235000020887 ketogenic diet Nutrition 0.000 description 53
- 235000003642 hunger Nutrition 0.000 description 24
- 230000037351 starvation Effects 0.000 description 24
- 238000011867 re-evaluation Methods 0.000 description 12
- 230000003087 glucogenic effect Effects 0.000 description 11
- 206010010071 Coma Diseases 0.000 description 10
- 206010010254 Concussion Diseases 0.000 description 10
- 235000014633 carbohydrates Nutrition 0.000 description 10
- 230000009514 concussion Effects 0.000 description 10
- 210000004556 brain Anatomy 0.000 description 9
- 239000000194 fatty acid Substances 0.000 description 8
- 230000035611 feeding Effects 0.000 description 8
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- 235000016709 nutrition Nutrition 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 208000007976 Ketosis Diseases 0.000 description 6
- 235000021196 dietary intervention Nutrition 0.000 description 6
- 206010015037 epilepsy Diseases 0.000 description 6
- 230000003345 hyperglycaemic effect Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 235000012054 meals Nutrition 0.000 description 6
- 230000004060 metabolic process Effects 0.000 description 6
- 210000002381 plasma Anatomy 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 208000019695 Migraine disease Diseases 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000035861 hyperketonemia Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 208000025978 Athletic injury Diseases 0.000 description 4
- 206010022489 Insulin Resistance Diseases 0.000 description 4
- 208000008348 Post-Concussion Syndrome Diseases 0.000 description 4
- 206010041738 Sports injury Diseases 0.000 description 4
- 208000003443 Unconsciousness Diseases 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 235000020934 caloric restriction Nutrition 0.000 description 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 230000003292 diminished effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 206010000410 Acetonaemia Diseases 0.000 description 3
- 206010019196 Head injury Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- AOWPVIWVMWUSBD-RNFRBKRXSA-N [(3r)-3-hydroxybutyl] (3r)-3-hydroxybutanoate Chemical compound C[C@@H](O)CCOC(=O)C[C@@H](C)O AOWPVIWVMWUSBD-RNFRBKRXSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 235000019577 caloric intake Nutrition 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000001610 euglycemic effect Effects 0.000 description 3
- 230000002641 glycemic effect Effects 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 230000002361 ketogenic effect Effects 0.000 description 3
- 230000004140 ketosis Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 150000004667 medium chain fatty acids Chemical class 0.000 description 3
- 229940057917 medium chain triglycerides Drugs 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 208000010444 Acidosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000007950 acidosis Effects 0.000 description 2
- 208000026545 acidosis disease Diseases 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000004153 glucose metabolism Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical group CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 235000021085 polyunsaturated fats Nutrition 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 235000000891 standard diet Nutrition 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- WTKMPKREPYCDPG-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-hydroxybutanoate Chemical class CCC(O)C(=O)OCC(O)CO WTKMPKREPYCDPG-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000219823 Medicago Species 0.000 description 1
- 206010027603 Migraine headaches Diseases 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 206010039203 Road traffic accident Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 235000021074 carbohydrate intake Nutrition 0.000 description 1
- 230000007963 carbohydrate restriction Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 235000013350 formula milk Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000009525 mild injury Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 235000021084 monounsaturated fats Nutrition 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 229940033080 omega-6 fatty acid Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229940116369 pancreatic lipase Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 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
- 239000010452 phosphate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15/404,396 | 2017-01-12 | ||
| US15/404,396 US9925164B1 (en) | 2017-01-12 | 2017-01-12 | Glyceryl 3-hydroxybutyrates for traumatic brain injury |
| PCT/US2017/063853 WO2018132189A1 (en) | 2017-01-12 | 2017-11-30 | Glyceryl 3-hydroxybutyrates for traumatic brain injury |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA3046355A1 CA3046355A1 (en) | 2018-07-19 |
| CA3046355C true CA3046355C (en) | 2023-08-01 |
Family
ID=61633011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3046355A Active CA3046355C (en) | 2017-01-12 | 2017-11-30 | Glyceryl 3-hydroxybutyrates for traumatic brain injury |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US9925164B1 (enExample) |
| EP (1) | EP3568129A4 (enExample) |
| JP (1) | JP7278593B2 (enExample) |
| KR (1) | KR102443942B1 (enExample) |
| CN (1) | CN110114067A (enExample) |
| BR (1) | BR112019014128A2 (enExample) |
| CA (1) | CA3046355C (enExample) |
| IL (1) | IL267934B2 (enExample) |
| MX (1) | MX391851B (enExample) |
| MY (1) | MY207193A (enExample) |
| WO (1) | WO2018132189A1 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11103470B2 (en) | 2017-11-22 | 2021-08-31 | Axcess Global Sciences, Llc | Non-racemic beta-hydroxybutyrate compounds and compositions enriched with the R-enantiomer and methods of use |
| US11241403B2 (en) | 2016-03-11 | 2022-02-08 | Axcess Global Sciences, Llc | Beta-hydroxybutyrate mixed salt compositions and methods of use |
| US11202769B2 (en) | 2017-11-22 | 2021-12-21 | Axcess Global Sciences, Llc | Ketone body esters of s-beta-hydroxybutyrate and/or s-1,3-butanediol for modifying metabolic function |
| US11026929B2 (en) | 2016-04-19 | 2021-06-08 | Keto Patent Group, Inc. | Administration of berberine metabolites |
| CA3021784A1 (en) * | 2016-04-19 | 2017-10-26 | Keto Patent Group, Inc. | Administration of butyrate, beta-hydroxybutyrate, and related compounds in humans |
| US11806324B2 (en) | 2018-04-18 | 2023-11-07 | Axcess Global Sciences, Llc | Beta-hydroxybutyric acid compositions and methods for oral delivery of ketone bodies |
| US12109182B2 (en) | 2016-04-19 | 2024-10-08 | Axcess Global Sciences, Llc | Administration of R-beta-hydroxybutyrate and related compounds in humans |
| US10925843B2 (en) | 2018-04-18 | 2021-02-23 | Axcess Global Sciences, Llc | Compositions and methods for keto stacking with beta-hydroxybutyrate and acetoacetate |
| US10376528B2 (en) | 2017-03-10 | 2019-08-13 | Tecton Group, Llc | Composition comprising ketone body and nicotinamide adenine dinucleotide modulator and methyl donor |
| US12171735B2 (en) | 2017-04-19 | 2024-12-24 | Axcess Global Sciences, Llc | Administration of butyrate, beta-hydroxybutyrate, cannabidiol, and related compounds in humans |
| GB201715654D0 (en) | 2017-09-27 | 2017-11-08 | Tdeltas Ltd | Method of treatment |
| US12090129B2 (en) | 2017-11-22 | 2024-09-17 | Axcess Global Sciences, Llc | Non-racemic beta-hydroxybutyrate compounds and compositions enriched with the R-enantiomer and methods of use |
| US11944598B2 (en) | 2017-12-19 | 2024-04-02 | Axcess Global Sciences, Llc | Compositions containing s-beta-hydroxybutyrate or non-racemic mixtures enriched with the s-enatiomer |
| US12329734B2 (en) | 2017-12-19 | 2025-06-17 | Axcess Global Sciences, Llc | Use of S-beta-hydroxybutyrate compounds for induction and maintenance of flow |
| US12091383B2 (en) * | 2019-01-17 | 2024-09-17 | Ketolipix Therapeutics Gmbh | Method for producing lipids comprising structural units based on glycerides of hydroxycarboxylc acids |
| JP7235873B2 (ja) * | 2019-01-17 | 2023-03-08 | アイオーアイ オレオ ゲーエムベーハー | ヒドロキシカルボン酸のグリセリドの製造方法 |
| US12472200B2 (en) | 2019-05-15 | 2025-11-18 | Axcess Global Sciences, Llc | Autobiotic compositions and method for promoting healthy gut microbiome |
| IL288343B2 (en) * | 2019-05-30 | 2024-04-01 | Neuroenergy Ventures Inc | Glyceryl tris (beta-hydroxybutyrate) and neuronal transient ischemic attacks |
| WO2020249195A1 (de) * | 2019-06-12 | 2020-12-17 | Ioi Oleo Gmbh | Verfahren zur herstellung von polyolbasierten estern von ketocarbonsäuren |
| CN114008015B (zh) * | 2019-06-12 | 2024-02-20 | 凯托利皮克斯治疗有限责任公司 | 羟基羧酸多元醇酯、特别是聚甘油酯的制备方法 |
| US11969430B1 (en) | 2023-03-10 | 2024-04-30 | Axcess Global Sciences, Llc | Compositions containing paraxanthine and beta-hydroxybutyrate or precursor for increasing neurological and physiological performance |
| US11950616B2 (en) | 2019-06-21 | 2024-04-09 | Axcess Global Sciences, Llc | Non-vasoconstricting energy-promoting compositions containing ketone bodies |
| US12167993B2 (en) | 2019-06-21 | 2024-12-17 | Axcess Global Sciences, Llc | Non-vasoconstricting energy-promoting compositions containing ketone bodies |
| JP2023543110A (ja) * | 2020-07-13 | 2023-10-13 | ケトリピックス セラポーティクス ゲーエムベーハー | オキソブタノールでエステル化されたポリグリセロールエステルを製造する方法 |
| US12186297B2 (en) | 2020-08-26 | 2025-01-07 | Axcess Global Sciences, Llc | Compositions and methods for increasing lean-to-fat mass ratio |
| US20240342121A1 (en) * | 2021-07-09 | 2024-10-17 | Georgia State University Research Foundation, Inc. | The use of beta-hydroxybutyrates for the treatment or prevention of aneurysms and dissections |
| IL312317B2 (en) | 2021-11-12 | 2025-04-01 | Arxada Ag | Polyol-derived compounds |
| US20250002446A1 (en) | 2021-11-26 | 2025-01-02 | Arxada Ag | Acetoacetate Based Ketals |
| WO2023139357A1 (en) * | 2022-01-18 | 2023-07-27 | Today Inc. | Molecules, nutritional formulations, and methods of providing nutritional support |
| US12023382B2 (en) | 2022-01-18 | 2024-07-02 | Today Inc. | Molecules, formulations, and methods for nutritional support of athletes, patients, and others |
| WO2023167989A2 (en) * | 2022-03-04 | 2023-09-07 | Guardian Biosciences, LLC | Compositions and methods to promote brain health |
| EP4605371A1 (en) | 2022-10-18 | 2025-08-27 | Arxada AG | Polyol-derived compounds |
| WO2025074001A2 (en) | 2023-10-05 | 2025-04-10 | Arxada Ag | Enzymatic reduction of acetoacetate |
| WO2025196156A1 (en) | 2024-03-20 | 2025-09-25 | Arxada Ag | Continuous hydrogenation process of acetoacetate esters |
| WO2025224319A1 (en) | 2024-04-25 | 2025-10-30 | Arxada Ag | Reduction of acetoacetate esters in the presence of amines |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4598203B2 (ja) | 1995-12-01 | 2010-12-15 | ビーティージー・インターナショナル・リミテッド | 脳機能改善剤 |
| US6323237B1 (en) | 1997-03-17 | 2001-11-27 | Btg International Limited | Therapeutic compositions |
| JP4740426B2 (ja) * | 1997-03-17 | 2011-08-03 | ビーティージー・インターナショナル・リミテッド | 治療用組成物 |
| GB0420856D0 (en) * | 2004-09-20 | 2004-10-20 | Ketocytonyx Inc | Cns modulators |
| ES2548700T3 (es) | 2005-05-26 | 2015-10-20 | The Regents Of The University Of Colorado, A Body Corporate | Inhibición de la vía alternativa del complemento para el tratamiento de lesión cerebral traumática, lesión de médula espinal y afecciones relacionadas |
| KR20090003148A (ko) | 2006-04-03 | 2009-01-09 | 액세라인크 | 나이와 관련된 기억 손상의 치료를 위한 케톤 생성조성물의 용도 |
| WO2008005818A1 (en) * | 2006-06-30 | 2008-01-10 | Stepan Co | Glyceride esters for the treatment of diseases associated with reduced neuronal metabolism of glucose |
| CA2684213A1 (en) | 2007-04-12 | 2008-10-23 | Regents Of The University Of Minnesota | Ischemia/reperfusion protection compositions and methods of using |
| JP2009173766A (ja) | 2008-01-24 | 2009-08-06 | Ono Kogei Kk | 炭素繊維含有コーティング組成物およびその調製方法 |
| US8642654B2 (en) | 2009-04-16 | 2014-02-04 | Isis Innovation Limited | Hydroxybutyrate ester and medical use thereof |
| EA201190115A1 (ru) | 2009-01-24 | 2012-02-28 | ФИТОФАРМ ПиЭлСи | Лечение расстройств, опосредованных нейротрофическим фактором |
| GB201002983D0 (en) * | 2010-02-22 | 2010-04-07 | Tdeltas Ltd | Nutritinal composition |
| CA2873057C (en) | 2011-05-09 | 2020-02-25 | University Of South Florida | The use of ketone esters for prevention of cns oxygen toxicity |
| US20140072654A1 (en) | 2011-12-23 | 2014-03-13 | Savind, Inc. | Cancer with metabolic therapy and hyperbaric oxygen |
| FR2997302B1 (fr) | 2012-10-29 | 2015-02-06 | Assist Publ Hopitaux De Paris | Prevention et traitement des deficits en pyruvate deshydrogenase |
| DK2914251T3 (da) | 2012-11-05 | 2019-11-04 | Us Health | Ketonlegemer til beskyttelse af væv mod beskadigelse som følge af ioniseringsstråling |
| EP2925308B1 (en) | 2012-11-28 | 2019-12-25 | University Of South Florida | Targeting cancer with metabolic therapy and hyperbaric oxygen |
| PE20151949A1 (es) | 2013-03-19 | 2016-01-05 | Univ South Florida | Composiciones y metodos para producir cetosis elevada y sostenida |
| WO2015034812A2 (en) * | 2013-09-04 | 2015-03-12 | Beth Israel Deaconess Medical Center | A new ketogenic diet and its use in treating the critically ill |
| CA2973342A1 (en) | 2014-01-13 | 2015-10-15 | University Of South Florida | Methods of sustaining dietary ketosis and its effects on lipid profile |
| US20160078782A1 (en) | 2014-09-17 | 2016-03-17 | The Trustees Of Boston College | Glucose Ketone Index for MetabolicTherapy |
| US9364456B1 (en) | 2015-06-30 | 2016-06-14 | University Of South Florida | Ketone esters for treatment of angelman syndrome |
| WO2017011294A1 (en) | 2015-07-10 | 2017-01-19 | Cognate Nutritionals, Inc. | Prophylaxis and mitigation of migraine headaches using medium chain triglycerides, ketone esters, and other ketogenic sources |
| US10292952B2 (en) | 2016-03-11 | 2019-05-21 | Axcess Global Sciences, Llc | Mixed salt compositions for maintaining or restoring electrolyte balance while producing elevated and sustained ketosis |
| WO2017165445A1 (en) | 2016-03-21 | 2017-09-28 | Csilla Ari D'agostino | Administration of exogenous ketone to lower blood glucose |
| US10376482B2 (en) | 2016-04-03 | 2019-08-13 | Franco Cavaleri | Butyrate and beta-hydroxybutyrate compositions |
| CA3021784A1 (en) | 2016-04-19 | 2017-10-26 | Keto Patent Group, Inc. | Administration of butyrate, beta-hydroxybutyrate, and related compounds in humans |
| WO2018009208A1 (en) | 2016-07-08 | 2018-01-11 | Cognate Nutritionals, Inc. | Nutritional mitiggation of the cns effects of traumatic brain injury |
| US10588877B2 (en) | 2016-07-21 | 2020-03-17 | Savind, Inc. | Compositions comprising β-hydroxybutyric acid and salt, and methods of using the same |
| US20180057846A1 (en) | 2016-08-30 | 2018-03-01 | KetoneAid Inc. | Partially buffered free acid and/or ketone blend for rapid onset ketosis and metabolic therapy |
| US20180055797A1 (en) | 2016-08-31 | 2018-03-01 | KetoneAid Inc. | Non-racemic ketone salts for rapid-onset nutritional ketosis and metabolic therapy |
| CA3036688A1 (en) | 2016-09-12 | 2018-03-15 | University Of South Florida | Neuroregeneration improved by ketone |
-
2017
- 2017-01-12 US US15/404,396 patent/US9925164B1/en active Active
- 2017-11-30 KR KR1020197020924A patent/KR102443942B1/ko active Active
- 2017-11-30 WO PCT/US2017/063853 patent/WO2018132189A1/en not_active Ceased
- 2017-11-30 EP EP17891194.7A patent/EP3568129A4/en active Pending
- 2017-11-30 IL IL267934A patent/IL267934B2/en unknown
- 2017-11-30 MY MYPI2019003665A patent/MY207193A/en unknown
- 2017-11-30 CN CN201780080457.XA patent/CN110114067A/zh active Pending
- 2017-11-30 CA CA3046355A patent/CA3046355C/en active Active
- 2017-11-30 MX MX2019008269A patent/MX391851B/es unknown
- 2017-11-30 BR BR112019014128-6A patent/BR112019014128A2/pt not_active Application Discontinuation
- 2017-11-30 JP JP2019536598A patent/JP7278593B2/ja active Active
-
2018
- 2018-03-01 US US15/909,240 patent/US10736867B2/en active Active
-
2020
- 2020-06-10 US US16/897,349 patent/US11638702B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| KR20190104546A (ko) | 2019-09-10 |
| US11638702B2 (en) | 2023-05-02 |
| US20180193300A1 (en) | 2018-07-12 |
| EP3568129A4 (en) | 2020-12-09 |
| US9925164B1 (en) | 2018-03-27 |
| IL267934B1 (en) | 2024-05-01 |
| IL267934A (en) | 2019-09-26 |
| MX391851B (es) | 2025-03-21 |
| CA3046355A1 (en) | 2018-07-19 |
| MY207193A (en) | 2025-02-05 |
| JP2020504134A (ja) | 2020-02-06 |
| MX2019008269A (es) | 2019-09-13 |
| IL267934B2 (en) | 2024-09-01 |
| US20200297686A1 (en) | 2020-09-24 |
| WO2018132189A1 (en) | 2018-07-19 |
| CN110114067A (zh) | 2019-08-09 |
| KR102443942B1 (ko) | 2022-09-15 |
| JP7278593B2 (ja) | 2023-05-22 |
| US10736867B2 (en) | 2020-08-11 |
| EP3568129A1 (en) | 2019-11-20 |
| BR112019014128A2 (pt) | 2020-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11638702B2 (en) | Glyceryl 3-hydroxybutyrates for traumatic brain injury | |
| EP3558458B1 (en) | Glyceryl 3-hydroxybutyrates for migraine symptom management | |
| Martinez | Restoring the DHA levels in the brains of Zellweger patients | |
| JP2020504134A5 (enExample) | ||
| US20200108040A1 (en) | Agent for improving brain function and agent for preventing or treating cognitive impairment | |
| Jahromi et al. | Islamic fasting and multiple sclerosis | |
| Sears et al. | Therapeutic uses of high-dose omega-3 fatty acids to treat comatose patients with severe brain injury | |
| Lin et al. | Application of ketogenic diets for pediatric neurocritical care | |
| Vining | The ketogenic diet | |
| Arora et al. | Phase I single center trial of ketogenic diet for adults with traumatic brain injury | |
| US20030096736A1 (en) | Lactoferrin for age related disorders in humans | |
| Lotfi et al. | Biological activities of astaxanthin in the treatment of neurodegenerative diseases | |
| Keskin et al. | Protein substitutions as new-generation pharmanutrition approach to managing phenylketonuria | |
| Maltese et al. | Ketogenic diet as antiepileptic therapy: administration and formulas | |
| Kahraman et al. | Successful management of rhabdomyolysis with triheptanoin in a child with severe long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency | |
| HK40012461A (en) | Glyceryl 3-hydroxybutyrates for traumatic brain injury | |
| Kuźniar et al. | Ketogenic diet and intermittent fasting-impact on body weight and various diseases | |
| CN1969675A (zh) | 治疗癫痫的饮食配方 | |
| Quertinmount et al. | A Novel Approach to Treating Alzheimer's Disease | |
| Raj et al. | KETOGENIC DIET IN EPILEPSY | |
| Hu et al. | Impact of zinc supplementation on the clinical outcomes in critically ill patients: a systematic review and meta-analysis | |
| Tufano et al. | 188/Neonatal and Perinatal Medicine | |
| CN121102248A (zh) | 一种组合物及其制备方法和在保护大脑健康中的应用 | |
| Gruenwald et al. | Efficacy and tolerability of mussel-Lyprinol® omega-3-complex on inflammatory rheumatoid disorders | |
| grief will become a Major | MENTAL DISORDERS FOR EVERYONE |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |
|
| EEER | Examination request |
Effective date: 20210831 |