CN113855656A - Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory - Google Patents
Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory Download PDFInfo
- Publication number
- CN113855656A CN113855656A CN202111308364.2A CN202111308364A CN113855656A CN 113855656 A CN113855656 A CN 113855656A CN 202111308364 A CN202111308364 A CN 202111308364A CN 113855656 A CN113855656 A CN 113855656A
- Authority
- CN
- China
- Prior art keywords
- tetrahydrocurcumin
- tween
- solid dispersion
- memory
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LBTVHXHERHESKG-UHFFFAOYSA-N tetrahydrocurcumin Chemical compound C1=C(O)C(OC)=CC(CCC(=O)CC(=O)CCC=2C=C(OC)C(O)=CC=2)=C1 LBTVHXHERHESKG-UHFFFAOYSA-N 0.000 title claims abstract description 119
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000007962 solid dispersion Substances 0.000 claims abstract description 20
- 210000005013 brain tissue Anatomy 0.000 claims description 21
- 238000012360 testing method Methods 0.000 claims description 19
- 239000000047 product Substances 0.000 claims description 15
- 229920000136 polysorbate Polymers 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 10
- 229920000053 polysorbate 80 Polymers 0.000 claims description 10
- 102100023460 Choline O-acetyltransferase Human genes 0.000 claims description 9
- 102100022033 Presenilin-1 Human genes 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000012876 carrier material Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 210000002569 neuron Anatomy 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 150000005846 sugar alcohols Polymers 0.000 claims description 4
- 239000012085 test solution Substances 0.000 claims description 4
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000012982 microporous membrane Substances 0.000 claims description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000012088 reference solution Substances 0.000 claims description 2
- 239000013558 reference substance Substances 0.000 claims description 2
- 239000012488 sample solution Substances 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000009210 therapy by ultrasound Methods 0.000 claims description 2
- 101150054987 ChAT gene Proteins 0.000 claims 1
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 abstract description 22
- 229940109262 curcumin Drugs 0.000 abstract description 16
- 235000012754 curcumin Nutrition 0.000 abstract description 11
- 239000004148 curcumin Substances 0.000 abstract description 11
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 abstract description 11
- 230000006870 function Effects 0.000 abstract description 3
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 8
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 238000012347 Morris Water Maze Methods 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 210000003710 cerebral cortex Anatomy 0.000 description 6
- 230000000971 hippocampal effect Effects 0.000 description 6
- 108010036933 Presenilin-1 Proteins 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 5
- 210000001320 hippocampus Anatomy 0.000 description 5
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 4
- 102100021257 Beta-secretase 1 Human genes 0.000 description 4
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 4
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 4
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 4
- 235000003373 curcuma longa Nutrition 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 229940044519 poloxamer 188 Drugs 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 4
- 229960002646 scopolamine Drugs 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- 235000003392 Curcuma domestica Nutrition 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 235000013976 turmeric Nutrition 0.000 description 3
- UEPVWRDHSPMIAZ-IZTHOABVSA-N (1e,4z,6e)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one Chemical compound C1=C(O)C(OC)=CC(\C=C\C(\O)=C\C(=O)\C=C\C=2C=CC(O)=CC=2)=C1 UEPVWRDHSPMIAZ-IZTHOABVSA-N 0.000 description 2
- 102000012440 Acetylcholinesterase Human genes 0.000 description 2
- 108010022752 Acetylcholinesterase Proteins 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- 244000008991 Curcuma longa Species 0.000 description 2
- HJTVQHVGMGKONQ-LUZURFALSA-N Curcumin II Natural products C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=CC(O)=CC=2)=C1 HJTVQHVGMGKONQ-LUZURFALSA-N 0.000 description 2
- RSAHICAPUYTWHW-UHFFFAOYSA-N Hexahydrocurcumin Chemical compound C1=C(O)C(OC)=CC(CCC(O)CC(=O)CCC=2C=C(OC)C(O)=CC=2)=C1 RSAHICAPUYTWHW-UHFFFAOYSA-N 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229940022698 acetylcholinesterase Drugs 0.000 description 2
- JYTVKRNTTALBBZ-UHFFFAOYSA-N bis demethoxycurcumin Natural products C1=CC(O)=CC=C1C=CC(=O)CC(=O)C=CC1=CC=CC(O)=C1 JYTVKRNTTALBBZ-UHFFFAOYSA-N 0.000 description 2
- PREBVFJICNPEKM-YDWXAUTNSA-N bisdemethoxycurcumin Chemical compound C1=CC(O)=CC=C1\C=C\C(=O)CC(=O)\C=C\C1=CC=C(O)C=C1 PREBVFJICNPEKM-YDWXAUTNSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- NMRUIRRIQNAQEB-UHFFFAOYSA-N demethoxycurcumin Natural products OC(=CC(C=CC1=CC(=C(C=C1)O)OC)=O)C=CC1=CC=C(C=C1)O NMRUIRRIQNAQEB-UHFFFAOYSA-N 0.000 description 2
- YXAKCQIIROBKOP-UHFFFAOYSA-N di-p-hydroxycinnamoylmethane Natural products C=1C=C(O)C=CC=1C=CC(=O)C=C(O)C=CC1=CC=C(O)C=C1 YXAKCQIIROBKOP-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- UEPVWRDHSPMIAZ-UHFFFAOYSA-N p-hydroxycinnamoyl feruloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(O)=CC(=O)C=CC=2C=CC(O)=CC=2)=C1 UEPVWRDHSPMIAZ-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000234299 Zingiberaceae Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MUYJSOCNDLUHPJ-UHFFFAOYSA-N bishydrocurcumin Natural products C1=C(O)C(OC)=CC(CCC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 MUYJSOCNDLUHPJ-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 108010010165 curculin Proteins 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- MUYJSOCNDLUHPJ-XVNBXDOJSA-N dihydrocurcumin Chemical compound C1=C(O)C(OC)=CC(CCC(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 MUYJSOCNDLUHPJ-XVNBXDOJSA-N 0.000 description 1
- BWHPKBOLJFNCPW-UHFFFAOYSA-N dihydrocurcumin Natural products C1=C(O)C(OC)=CC(CCC(=O)C=C(O)C=CC=2C=C(OC)C(O)=CC=2)=C1 BWHPKBOLJFNCPW-UHFFFAOYSA-N 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000009920 food preservation Methods 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- -1 oxygen free radical Chemical class 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Images
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
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention provides application of tetrahydrocurcumin in preparing a medicine or a health-care product for improving memory. The invention also provides a solid dispersion of tetrahydrocurcumin, a preparation method and application thereof. Pharmacodynamics proves that the tetrahydrocurcumin has the function of obviously improving memory, and the efficacy is obviously superior to that of curcumin under the same dosage.
Description
The application is a divisional application provided by an invention patent application with the application number of 201810468409.4 and the application date of 2018, 05 and 16.
Technical Field
The invention relates to a new application of tetrahydrocurcumin, in particular to an application in preparing a medicine or a health-care product for improving memory.
Background
Memory impairment refers to a state in which an individual is unable to remember or recall information or skills, either permanently or temporarily, due to pathophysiological or contextual causes. The memory includes memory, keeping and reappearance, and has close relation with the psychoneural functions. Memory is divided into transient (within minutes, seconds) short term (days) and long term (months, years) memory based on neurophysiological and biochemical studies. Memory and forgetting are concomitant, and forgetting has temporal regularity and selectivity. The newly-learned materials are forgotten most quickly and gradually develop into a long-term forgetting, and the things which once arouse high attention are difficult to forget.
Turmeric (rhizomacurcumae longae) is a dried rhizome of curcuma longa (curcumae longae L.) belonging to the family zingiberaceae, mainly produced in japan, usa, africa, china, etc., and used in india for seasoning, food preservation, beauty treatment and medicine. The chemical components of the turmeric mainly comprise curcumin and volatile oil, and in addition, sugar, sterol and the like. The Curcumin mainly comprises Curcumin (curculin), demethoxycurcumin (demethoxycurcumin) and bisdemethoxycurcumin (bisdemethoxycurcumin). Curcumin is a main effective component in turmeric rhizome, has various pharmacological actions such as anti-inflammation, antioxidation, oxygen free radical elimination, liver protection, fibrosis resistance and the like, and is widely concerned at home and abroad. Curcumin is rapidly metabolized in the body to glucuronic acid conjugates, sulfate conjugates, dihydrocurcumin, tetrahydrocurcumin and hexahydrocurcumin, which are converted to tetrahydrocurcumin.
Tetrahydrocurcumin (THC) is also widely regarded at home and abroad as the most active and major metabolite produced during the in vivo metabolism of curcumin. Research shows that the tetrahydrocurcumin has pharmacological activities of protecting liver, resisting tumor, resisting oxidation, reducing blood sugar, reducing blood fat and the like. No report that tetrahydrocurcumin can improve memory is found.
Disclosure of Invention
The invention aims to provide application of tetrahydrocurcumin in preparing a medicine or a health-care product for improving memory.
The invention provides an application of tetrahydrocurcumin as a unique active ingredient in preparing a medicament or a health-care product for improving memory;
the drug can increase CHAT protein content in brain tissue, reduce A beta protein content, reduce PS1 protein content and/or protect neurons.
Furthermore, the medicine is a medicine for improving the memory acquisition disorder and improving the memory.
Furthermore, the medicament is prepared into a common preparation in pharmacy by taking tetrahydrocurcumin as a unique active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Further, the formulation is a solid dispersion.
The invention also provides a tetrahydrocurcumin solid dispersion which is prepared from the following raw and auxiliary materials in parts by weight:
1 part of tetrahydrocurcumin, 1-20 parts of water-soluble carrier material and 0.1-15 parts of synergist;
wherein the water-soluble carrier material is selected from one or more of polyethylene glycol, poloxamer and polyvinylpyrrolidone; the synergist is selected from one or more of polyalcohol, lecithin, and Tween.
Further, the polyalcohol is one or a mixture of more than one of ethylene glycol, propylene glycol and glycerol; the tween is one or a mixture of more than one of tween 20, tween 40, tween 60, tween 65, tween 80 and tween 85.
Further, the solid dispersion is prepared from the following raw and auxiliary materials in parts by weight:
1 part of tetrahydrocurcumin, 02-12 parts of polyethylene glycol 40078 and 10 parts of tween 800.5.
The present invention also provides a method for preparing the aforementioned solid dispersion, which comprises the steps of:
(1) weighing raw and auxiliary materials according to the proportion;
(2) taking tetrahydrocurcumin, a water-soluble carrier material and a synergist, and preparing the solid dispersion by adopting a solvent method or a melting method.
The invention also provides a detection method of the solid dispersion, which adopts high performance liquid chromatography for detection and comprises the following steps:
a. preparation of control solutions: precisely weighing appropriate amount of tetrahydrocurcumin reference substance, and adding mobile phase to obtain solution containing 10 μ g per 1 ml;
b. preparation of a test solution: precisely weighing 150mg of the content of the product, placing the content in a 10ml volumetric flask, precisely adding a mobile phase to a constant volume, shaking up, carrying out ultrasonic treatment for 1-10 minutes, taking out, placing the product to room temperature, precisely sucking the product in the 1ml to 10ml volumetric flask, fixing the volume of the mobile phase, and filtering the product by using a 0.45 mu m microporous membrane to obtain a filtrate, namely a test solution; the ultrasonic power is not lower than 100W, and the frequency is not lower than 40 kHz;
the determination method comprises the following steps: precisely sucking 5-15 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, and measuring;
c. chromatographic condition and system adaptability test: octadecylsilane chemically bonded silica is used as a filler, and acetonitrile: 0.02% -1% phosphoric acid or glacial acetic acid solution (30-60): 70-40 is a mobile phase, the detection wavelength is 280nm, and the theoretical plate number is not less than 1000-3000 calculated according to tetrahydrocurcumin.
In conclusion, pharmacodynamics proves that the tetrahydrocurcumin has the function of obviously improving memory, the efficacy is obviously superior to that of curcumin under the same dosage, and the clinical application prospect is excellent.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 shows HE staining of mouse cerebral cortex.
Figure 2 is mouse brain hippocampal HE staining.
Detailed Description
The raw materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products.
Example 1 Tetrahydrocurcumin/PEG/Tween 80 solid Dispersion
TABLE 1 charging ratio of tetrahydrocurcumin/PEG/Tween 80 solid dispersion
The preparation method comprises the following steps: the preparation method adopts a melting method. Feeding the components according to the proportion in the table 1, weighing PEG4000 and Tween 80, heating at 70-80 ℃ until the components are completely melted, adding tetrahydrocurcumin, stirring uniformly, continuously heating until the tetrahydrocurcumin is completely dissolved, quickly placing into an ice water bath for cooling and curing, and crushing to obtain the four-component tetrahydrocurcumin/PEG/Tween 80 solid dispersion.
Example 2 Tetrahydrocurcumin/poloxamer 188/Tween 80 solid Dispersion
TABLE 2 charging ratio of tetrahydrocurcumin/poloxamer 188/tween 80 solid dispersion
The preparation method comprises the following steps: the preparation method adopts a melting method. Feeding the components according to the proportion shown in the table 2, weighing poloxamer 188 and tween 80, heating at 70-80 ℃ until the components are completely melted, adding tetrahydrocurcumin, stirring uniformly, continuously heating until the tetrahydrocurcumin is completely dissolved, quickly placing into an ice-water bath for cooling and curing, and crushing to obtain the four-component tetrahydrocurcumin/poloxamer 188/tween 80 solid dispersion.
The beneficial effects of the present invention are demonstrated by specific pharmacodynamic tests below.
Test example 1 Tetrahydrocurcumin (THC) and curcumin (Cur) improve learning and memory function of scopolamine-injured mice with memory acquisition disorder
1. Experimental methods
(1) Experimental animal Kunming mouse, male, 4 weeks old, purchased from Sichuan academy of traditional Chinese medicine.
(2) The dosage and grouping of the medicines are as follows: normal control, adjuvant control group, model group, tetrahydrocurcumin solid dispersant (THC) group (200mg/kg), curcumin solid dispersant group (200mg/kg), each group containing 12 animals.
The administration mode comprises the following steps: pre-test dosing, gavage dosing, 0.1ml/10g body weight/day, total test sample dosing time of 35 days, and continued dosing during the Morris water maze test training period (10 days total). The normal control group is perfused with distilled water with the same volume, and the auxiliary material control group and the model group are perfused with menstruum with the same volume.
(3) Measurement index
(3.1) Morris water maze experiment-defined as voyage: after administration for 25 days, a water maze experiment was performed, in which the mouse was placed in a circular pool (120 cm in diameter, 50cm in height, 30cm in depth and 10cm from the top of the pool) with a circular platform (the surface of the platform was designed with some rough lines to facilitate the mouse to catch) about 6.5cm in diameter and 29cm in height, hidden under 1cm of water surface. The pool water was stained white with a dye and the time for the mouse to seek the platform was recorded (escape latency). If the platform is not found within 90s, the experimenter brings it up to the platform, and after staying for 5s, the experimenter returns to the rearing cage, and the escape latency is recorded as 90 s.
(3.2) Morris water maze experiment-space exploration experiment: and removing the platform in the morning of the next day after the positioning navigation is finished, enabling the animal to enter water at the position right opposite to the platform, recording the swimming track for 60s, and measuring the staying time and the swimming stroke of the animal in the quadrant of the platform. And recording the times of crossing the original platform.
(3.3) before the water maze training, except the normal control group, the other groups are injected with 3mg/kg of scopolamine in the abdominal cavity, and the scopolamine is continuously given every day in the whole training and testing period.
(3.4) after the water maze experiment is finished, taking mouse brain tissue, staining the mouse brain tissue by an immunohistochemical method, observing the mouse hippocampal tissue under a light microscope, and determining the expression strength of choline acetyltransferase (CHAT), acetylcholinesterase (AchE) and intracerebral acetylcholine (Ach).
2. Results of the experiment
As can be seen from table 3, the time for the mice to find the platform was significantly prolonged (P <0.05, P <0.01) at days 8, 9 and 10 after the model group was modeled, compared to the control group; compared with the model group, the time for the THC group mice to find the platform at the 10 th day after the model building is obviously shortened (P <0.01), the time for the Cur group mice to find the platform at the 10 th day after the model building is shortened (P <0.05), and the THC and the Cur are shown to be capable of obviously improving the learning and memory capacity of the scopolamine mice.
TABLE 3 Effect of test substances on mouse latency
Note: model group compared to normal group, P <0.05, P < 0.01; the other groups compared with the model group, delta P <0.05 and delta P < 0.01.
As can be seen from table 4, compared with the control group, in the space exploration experiment of the model group on day 11 after the model building, the residence time of the mouse in the platform, the movement time of the effective area and the residence time in the first quadrant are all obviously shortened, (P < 0.01); compared with the model group, the THC group mice have obviously prolonged moving time in the effective area and retention time in the first quadrant (P <0.01), the Cur group mice have obviously prolonged moving time in the effective area and retention time in the first quadrant (P <0.05 and P <0.01 respectively), and the THC and Cur can obviously improve the space exploration memory capacity of the scopolamine mice.
TABLE 4 influence of test substances on the spatial exploration memory of mice
Note: model group compared to normal group, P <0.05, P < 0.01; the other groups compared with the model group, delta P <0.05 and delta P < 0.01.
The statistical results in table 5 show that compared with the adjuvant control group, the CHAT protein content in the mouse brain tissue of the model group is obviously reduced, and the statistical significance is very significant (P < 0.01). Compared with a model group, the CHAT protein content of the brain tissue of the mice in the THC group is obviously increased and has very obvious statistical significance (P <0.01), and the CHAT protein content of the brain tissue of the mice in the Cur group is increased and has obvious statistical significance (P < 0.05).
TABLE 5 Effect of test substances on CHAT mean optical Density of mouse brain tissue
Note: p <0.05 in the model group compared to the adjuvant group; compared with the model group, the THC group has the delta P <0.05 and the delta P < 0.01.
Experimental results prove that the tetrahydrocurcumin can effectively and obviously improve the memory acquisition disorder and improve the memory, has the drug effect obviously superior to that of curcumin under the same dosage and has excellent clinical application prospect.
Test example 2 improvement of learning and memory function of D-galactose combined with aluminum trichloride impaired memory acquisition disorder mice by Tetrahydrocurcumin (THC)
1. Experimental methods
(1) Male Kunming mice of 4 weeks old were randomly divided into a normal control group, an adjuvant control group, a model group, and a tetrahydrocurcumin solid dispersant (THC) (200mg/kg) group, each of which had 12 animals.
Pre-test dosing, gavage dosing, 0.1ml/10g body weight/day, total test sample dosing time of 35 days, and continued dosing during the Morris water maze test training period (10 days total). The normal control group is perfused with distilled water with the same volume, and the auxiliary material control group and the model group are perfused with menstruum with the same volume.
The experimental AD modeling adopts ig AlCl3(20mg/kg) in combination with ip D-galactose (120 mg/kg). Daily gavage of AlCl3: 0.1ml/10g body weight, D-galactose injected intraperitoneally: 0.1ml/20g body weight. Normal control mice were modelled sequentially for 70 days with ig equal volume of MilliQ water (0.1ml/10g body weight) and ip equal volume of physiological saline (0.1ml/20g body weight).
(2) Measurement index
Morris water maze experiment-defined as voyage: after administration for 25 days, a water maze experiment was performed, in which the mouse was placed in a circular pool (120 cm in diameter, 50cm in height, 30cm in depth and 10cm from the top of the pool) with a circular platform (the surface of the platform was designed with some rough lines to facilitate the mouse to catch) about 6.5cm in diameter and 29cm in height, hidden under 1cm of water surface. The pool water was stained white with a dye and the time for the mouse to seek the platform was recorded (escape latency). If the platform is not found within 90s, the experimenter brings it up to the platform, and after staying for 5s, the experimenter returns to the rearing cage, and the escape latency is recorded as 90 s.
Morris water maze experiment-space exploration experiment: and removing the platform in the morning of the next day after the positioning navigation is finished, enabling the animal to enter water at the position right opposite to the platform, recording the swimming track for 60s, and measuring the staying time and the swimming stroke of the animal in the quadrant of the platform. And recording the times of crossing the original platform.
After the water maze experiment is finished, taking a mouse brain tissue, HE staining to observe the cell damage lesion degree of the mouse hippocampus and cortex, and observing the expression intensity of beta-Amyloid (Abeta, Amyloid beta-peptide), Amyloid-pro-beta-lyase 1(BACE) and Presenilin-1 (Presenilin-1, PS1) in the mouse hippocampus tissue after immunohistochemical staining.
2. Results of the experiment
As can be seen from table 6, compared with the control group, on day 10 of the water maze experiment, the time for the mouse to find the platform is obviously prolonged, the total movement distance is obviously increased, and the statistical significance is significant (P <0.05, P < 0.01); compared with the model group, the time for the THC group mice to find the platform at the 10 th day after the model building is obviously shortened (P <0.01), the total movement distance is obviously reduced (P <0.01), and the statistical significance is remarkable. Shows that THC can obviously improve the learning and memory ability of D-galactose combined with aluminum trichloride to damage mice.
TABLE 6 Effect of test substances on mouse latency
Note: model group vs. normal group<0.05，**P<0.01; the remaining set is compared to the model set,△P<0.05，△△P<0.01。
the statistical results in table 7 show that compared with the control group, the brain tissue Abeta protein content of the mouse in the model group is obviously increased, and the statistical significance is significant (P < 0.01). Compared with the model group, the brain tissue Abeta protein content of the mice in the THC group is obviously reduced, and the statistical significance is remarkable (P is less than 0.01).
TABLE 7 Effect of test substances on the mean optical Density of Abeta in mouse brain tissue
Note: p <0.05 in the model group compared to the adjuvant group; compared with the model group, the THC group has the delta P <0.05 and the delta P < 0.01.
The statistical result in Table 8 shows that the brain tissue PS-1 protein content of the model group mice is obviously increased compared with the normal control group, and the statistical significance is significant (P < 0.01). Compared with the model group, the brain tissue PS-1 protein content of the mice in the THC group is reduced, and the statistical significance is achieved (P is less than 0.05).
TABLE 8 Effect of test substances on the mean optical Density of mouse brain tissue PS-1
Note: p <0.05 in the model group compared to the adjuvant group; compared with the model group, the THC group has the delta P <0.05 and the delta P < 0.01.
The statistical results in Table 9 show that the content of BACE protein in brain tissue of mice in the model group is obviously increased compared with that in the normal control group, and the statistical significance is significant (P < 0.01). Compared with the model group, the brain tissue BACE protein content of the mice in the THC group has no obvious difference and has no statistical significance.
TABLE 9 test substance vs mouse brainEffect of tissue BACE average optical Density
Note: p <0.05 in the model group compared to the adjuvant group; compared with the model group, the THC group has the delta P <0.05 and the delta P < 0.01.
As shown in fig. 1 and 2, the results of HE staining of cerebral cortex and HE staining of hippocampus of mice showed that the normal control group: the brain tissue capsule is complete, each cell layer of the cortex is regularly and orderly arranged, the morphological structure is normal, the staining is clear, the nerve fiber is densely arranged, the hippocampus structure is complete, the neuron is regularly arranged, the cell number is not reduced or increased, wherein 1 (1/6) hippocampus DG area neuron generates a small amount of necrosis, the cell is triangular, and the staining is deep. Vehicle model group: the capsule of the brain tissue is complete, each cell layer of the cortex is arranged regularly and clearly, the nerve fibers are arranged densely, and 4 cases (4/6) of the brain tissue have disordered cerebral cortex cell arrangement and a small amount of centrum cell necrosis can be seen in the cortex and the hippocampal region respectively. Model group: in 5 cases (5/6) of the cerebral tissues in the group, the hippocampal regions all have different numbers of centrum cell necrosis, and the cells are triangular and are deeply dyed; the cells in the cerebral cortex are disorganized, and a small amount of microglial cell proliferation is observed. THC group: in 2(2/6) cases of this group, a small amount of centrum cell necrosis was observed in the cerebral cortex, cells in the hippocampal region were aligned and no cell proliferation or reduction was observed, and cells in the cerebral cortex and hippocampal region of the remaining tissues were aligned and no abnormality was observed.
Experimental results prove that the tetrahydrocurcumin can effectively increase the CHAT protein content of brain tissues, reduce the A beta protein content, reduce the PS1 protein content and/or protect neurons, improve the memory acquisition disorder and improve the memory.
In conclusion, the tetrahydrocurcumin can effectively improve memory and improve memory acquisition disorder, and provides a new choice for clinically improving the memory acquisition disorder.
Claims (9)
1. The application of tetrahydrocurcumin as the only active component in preparing the medicine or health-care product for improving the memory;
the drug can increase CHAT protein content in brain tissue, reduce A beta protein content, reduce PS1 protein content and/or protect neurons.
2. Use according to claim 1, characterized in that: the medicine is used for improving the memory acquisition disorder and improving the memory.
3. Use according to claim 1 or 2, characterized in that: the medicament is a common preparation in pharmacy prepared by taking tetrahydrocurcumin as a unique active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
4. Use according to claim 3, characterized in that: the formulation is a solid dispersion.
5. A tetrahydrocurcumin solid dispersion is characterized in that: the medicament is prepared from the following raw and auxiliary materials in parts by weight:
1 part of tetrahydrocurcumin, 1-20 parts of water-soluble carrier material and 0.1-15 parts of synergist;
wherein the water-soluble carrier material is selected from one or more of polyethylene glycol, poloxamer and polyvinylpyrrolidone; the synergist is selected from one or more of polyalcohol, lecithin, and Tween.
6. The solid dispersion of claim 5, wherein: the polyalcohol is one or more of ethylene glycol, propylene glycol and glycerol; the tween is one or a mixture of more than one of tween 20, tween 40, tween 60, tween 65, tween 80 and tween 85.
7. The solid dispersion of claim 6, wherein: the medicament is prepared from the following raw and auxiliary materials in parts by weight:
1 part of tetrahydrocurcumin, 02-12 parts of polyethylene glycol 40078 and 10 parts of tween 800.5.
8. A method of preparing the solid dispersion according to any one of claims 5 to 7, characterized by: it comprises the following steps:
(1) weighing raw and auxiliary materials according to the proportion;
(2) taking tetrahydrocurcumin, a water-soluble carrier material and a synergist, and preparing the solid dispersion by adopting a solvent method or a melting method.
9. The method for detecting a solid dispersion according to any one of claims 5 to 7, which comprises the steps of:
a. preparation of control solutions: precisely weighing appropriate amount of tetrahydrocurcumin reference substance, and adding mobile phase to obtain solution containing 10 μ g per 1 ml;
b. preparation of a test solution: precisely weighing 150mg of the content of the product, placing the content in a 10ml volumetric flask, precisely adding a mobile phase to a constant volume, shaking up, carrying out ultrasonic treatment for 1-10 minutes, taking out, placing the product to room temperature, precisely sucking the product in the 1ml to 10ml volumetric flask, fixing the volume of the mobile phase, and filtering the product by using a 0.45 mu m microporous membrane to obtain a filtrate, namely a test solution; the ultrasonic power is not lower than 100W, and the frequency is not lower than 40 kHz;
the determination method comprises the following steps: precisely sucking 5-15 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, and measuring;
c. chromatographic condition and system adaptability test: octadecylsilane chemically bonded silica is used as a filler, and acetonitrile: 0.02% -1% phosphoric acid or glacial acetic acid solution (30-60): 70-40 is a mobile phase, the detection wavelength is 280nm, and the theoretical plate number is not less than 1000-3000 calculated according to tetrahydrocurcumin.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017103438007 | 2017-05-16 | ||
| CN201710343800 | 2017-05-16 | ||
| CN201810468409.4A CN108853069A (en) | 2017-05-16 | 2018-05-16 | Purposes of the tetrahydro curcumin in the drug or health care product that preparation improves memory |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810468409.4A Division CN108853069A (en) | 2017-05-16 | 2018-05-16 | Purposes of the tetrahydro curcumin in the drug or health care product that preparation improves memory |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113855656A true CN113855656A (en) | 2021-12-31 |
Family
ID=64334495
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111308364.2A Pending CN113855656A (en) | 2017-05-16 | 2018-05-16 | Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory |
| CN202111069565.1A Pending CN113648292A (en) | 2017-05-16 | 2018-05-16 | Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory |
| CN201810468409.4A Pending CN108853069A (en) | 2017-05-16 | 2018-05-16 | Purposes of the tetrahydro curcumin in the drug or health care product that preparation improves memory |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111069565.1A Pending CN113648292A (en) | 2017-05-16 | 2018-05-16 | Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory |
| CN201810468409.4A Pending CN108853069A (en) | 2017-05-16 | 2018-05-16 | Purposes of the tetrahydro curcumin in the drug or health care product that preparation improves memory |
Country Status (1)
| Country | Link |
|---|---|
| CN (3) | CN113855656A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110261496B (en) * | 2019-04-17 | 2022-04-05 | 四川省中医药科学院 | Method for detecting content of tetrahydrocurcumin |
| CN113577045A (en) * | 2021-09-06 | 2021-11-02 | 四川省中医药转化医学中心 | Application of tetrahydrocurcumin in preparation of medicine for preventing and/or treating high altitude cognitive disorder |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058516A (en) * | 2009-11-18 | 2011-05-18 | 北京世纪博康医药科技有限公司 | Solid dispersion and preparation thereof |
| CN104739751A (en) * | 2013-12-26 | 2015-07-01 | 四川省中医药科学院 | Tetrahydrocurcumin solid dispersion and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011114350A2 (en) * | 2010-03-15 | 2011-09-22 | Laila Nutraceuticals | Boswellia oil, its fractions and compositions for enhancing brain function |
-
2018
- 2018-05-16 CN CN202111308364.2A patent/CN113855656A/en active Pending
- 2018-05-16 CN CN202111069565.1A patent/CN113648292A/en active Pending
- 2018-05-16 CN CN201810468409.4A patent/CN108853069A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058516A (en) * | 2009-11-18 | 2011-05-18 | 北京世纪博康医药科技有限公司 | Solid dispersion and preparation thereof |
| CN104739751A (en) * | 2013-12-26 | 2015-07-01 | 四川省中医药科学院 | Tetrahydrocurcumin solid dispersion and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| KWOK KIN CHENG等: "Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain", 《THE AAPS JOURNAL》 * |
| 廖利等: "四氢姜黄素的研究进展", 《世界科学技术-中医药现代化》 * |
| 梁艳红: "四氢姜黄素β-环糊精包和物的制备方法研究", 《化学工程与装备》 * |
| 赵苗等: "姜黄素对阿尔茨海默病模型小鼠记忆获得和巩固障碍的影响", 《湖北科技学院学报（医学版）》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113648292A (en) | 2021-11-16 |
| CN108853069A (en) | 2018-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Almeida et al. | Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice | |
| Kim et al. | p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments | |
| JP6353073B2 (en) | Composition for cell recovery and method for producing and using the same | |
| Li et al. | Evaluation of paeonol skin-target delivery from its microsponge formulation: in vitro skin permeation and in vivo microdialysis | |
| US20100093847A1 (en) | Anti-obesity active agent and anti-obesity method | |
| KR20110042314A (en) | Use of a chinese traditional medicinal composition for preparing medicine for promoting bone marrow-derived mesenchymal stem cell survival in vivo and cardiac muscle differentiation | |
| CN113855656A (en) | Application of tetrahydrocurcumin in preparation of medicine or health-care product for improving memory | |
| CN107811967A (en) | Anti-parasite medicine in-situ solidification sustained-release injector and preparation method thereof | |
| CN101890030B (en) | Composite capable of preventing bacteria, viruses, oxidation and pigment deposition | |
| Khorrami et al. | Tacrolimus ameliorates functional disturbances and oxidative stress in isoproterenol-induced myocardial infarction | |
| Yosipovitch | Pruritus | |
| CN104042655A (en) | Application of Chinese herb Pien Tze Huang and preparation thereof in preparation of drugs for treating non-alcoholic fatty liver disease (NAFLD) | |
| CN107205920A (en) | Injectable buprenorphine formulation | |
| Baskar et al. | Study on improving bioavailability ratio of anti-inflammatory compound from ginger through nano transdermal delivery | |
| KR101743960B1 (en) | G 19 Pharmaceutical composition for preventing treating or retarding Alzheimers disease or dementia comprising G protein-Coupled Receptor19 agonist as an active ingredient | |
| Ekong et al. | Co-administration of Rauwolfia vomitoria with Gongronema latifolium or Vernonia amygdalina on spatial learning, memory, and some bio-molecules | |
| Islam et al. | Clinicopathological studies on gentamicin toxicity in White Leghorn commercial layers | |
| KR102203325B1 (en) | Composition comprising Exosome Mimetics derived from Red Blood Cells for Material Delivery and Use Thereof | |
| WO2017106584A1 (en) | Treatment of central nervous system and mental disorders with agonists of beta-3 adrenoceptor | |
| CN102008536B (en) | Tripterygium wilfordii hook extract cataplasm and preparation method thereof | |
| Qu et al. | Induction of substantial myocardial regeneration by an active fraction of the Chinese herb Rosa laevigata Michx | |
| CN110063972A (en) | The application of Shexiang Baoxin Pills or Shexiang Baoxin Pills extract in preparation treatment neurodegenerative disease | |
| CN108743950A (en) | Insecticide and preparation method thereof | |
| CN1056748C (en) | Use of bolbostemmaoside A to prepare medicine for treatment of leukemia | |
| RU2674086C1 (en) | Method of modeling neurodegenerative diseases in adult laboratory rodents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211231 |
|
| RJ01 | Rejection of invention patent application after publication |