CN106038522A - Application of rhein in preparation of anti-depression medicines - Google Patents
Application of rhein in preparation of anti-depression medicines Download PDFInfo
- Publication number
- CN106038522A CN106038522A CN201610494641.6A CN201610494641A CN106038522A CN 106038522 A CN106038522 A CN 106038522A CN 201610494641 A CN201610494641 A CN 201610494641A CN 106038522 A CN106038522 A CN 106038522A
- Authority
- CN
- China
- Prior art keywords
- chrysophanic acid
- depression
- medicine
- salt
- chrysophanic
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 40
- 229940079593 drug Drugs 0.000 title claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 230000037396 body weight Effects 0.000 claims abstract description 14
- 239000004615 ingredient Substances 0.000 claims abstract description 6
- LQGUBLBATBMXHT-UHFFFAOYSA-N chrysophanol Chemical compound C1=CC=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O LQGUBLBATBMXHT-UHFFFAOYSA-N 0.000 claims description 189
- 239000000935 antidepressant agent Substances 0.000 claims description 42
- 230000001430 anti-depressive effect Effects 0.000 claims description 22
- 229940005513 antidepressants Drugs 0.000 claims description 17
- 239000007924 injection Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 239000000725 suspension Substances 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000000857 drug effect Effects 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 23
- 229960004801 imipramine Drugs 0.000 abstract description 16
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 abstract description 16
- 238000002474 experimental method Methods 0.000 abstract description 11
- 238000005516 engineering process Methods 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- 241000699670 Mus sp. Species 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 238000012048 forced swim test Methods 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000010171 animal model Methods 0.000 description 6
- 230000009182 swimming Effects 0.000 description 6
- 241000581650 Ivesia Species 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000000994 depressogenic effect Effects 0.000 description 4
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 4
- 229960002102 imipramine hydrochloride Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010054089 Depressive symptom Diseases 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- FPVGTPBMTFTMRT-NSKUCRDLSA-L fast yellow Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(N)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 FPVGTPBMTFTMRT-NSKUCRDLSA-L 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229920001491 Lentinan Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 2
- 229940022405 astaxanthin Drugs 0.000 description 2
- 235000013793 astaxanthin Nutrition 0.000 description 2
- 239000001168 astaxanthin Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002401 inhibitory 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
- 229940115286 lentinan Drugs 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 230000006996 mental state Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KQLDDLUWUFBQHP-UHFFFAOYSA-N Cordycepin Natural products C1=NC=2C(N)=NC=NC=2N1C1OCC(CO)C1O KQLDDLUWUFBQHP-UHFFFAOYSA-N 0.000 description 1
- 241000190633 Cordyceps Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 206010021703 Indifference Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 241000205407 Polygonum Species 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 240000001745 Rheum palmatum Species 0.000 description 1
- 235000008090 Rheum palmatum Nutrition 0.000 description 1
- 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001720 action spectrum Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- OFEZSBMBBKLLBJ-BAJZRUMYSA-N cordycepin Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)C[C@H]1O OFEZSBMBBKLLBJ-BAJZRUMYSA-N 0.000 description 1
- OFEZSBMBBKLLBJ-UHFFFAOYSA-N cordycepine Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)CC1O OFEZSBMBBKLLBJ-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001543 purgative effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
-
- 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
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
Abstract
The invention relates to the pharmacy technology, and particularly relates to application of rhein in preparation of anti-depression medicines. The anti-depression medicinal ingredient of the medicine is rhein or rhein salt, and the dosage is 0.01-100mg of rhein per kilogram of body weight or rhein salt equivalent to the amount of 0.01-100mg of rhein per kilogram of body weight; and the anti-depression effect can be generated in 60 minutes after the medicine is administrated. The medicine has the advantages of remarkable anti-depression effect, small dosage, quick response and the like. In a mammal mouse experiment, the rhein has a quick anti-depression effect stronger than that of a conventional anti-depression medicine imipramine, and is expected to become a novel quick and efficient anti-depression medicine.
Description
Technical field
The present invention relates to pharmaceutical technology, particularly to chrysophanic acid purposes in preparing anti-depression drug.
Background technology
Depression is also known as depressive disorder, low as main clinical characteristics with notable and lasting mental state.Clinical visible mental state
Low unbecoming with its situation, the downhearted of emotion can be from depressed to extremely grieved, and depression of feeling oneself inferior is the most pessimistic and worldweary,
Can there be suicidal attempt or behavior.Some cases has obvious anxiety and mobility intense, and severe patient may occur in which the essence such as hallucination, vain hope
God's disease symptoms.Outbreak continues at least two weeks more than, up to the several years every time.Majority of cases has the tendency of recurrent exerbation, shows effect every time
Great majority can be alleviated, and part can have residual symptoms or transfer to chronic.
Drug therapy is the primary treatment measure of the above paralepsy of moderate.Traditional tricyclic antidepressants, tetracyclic antidepressants
Relatively big due to untoward reaction with oxidase inhibitor, application significantly reduces.The antidepressants of a line are main the most clinically
Including selective serotonin reuptake inhibitor, 5-hydroxy tryptamine and NRI etc., but use this
Class drug effect is slow, and action spectrum is narrow, easily recurs after drug withdrawal.At present, whole industry is all little, more in research and development instant effect, side effect
Effective medicine.
Chrysophanic acid is a kind of chemical substance, for coffee-like needle, fusing point 321-322 DEG C, water insoluble, can be dissolved in pyridine,
Sodium bicarbonate aqueous solution, is slightly soluble in ethanol, benzene, aminoform, ether and petroleum ether.Chrysophanic acid derive from polygonum rheum palmatum and
The positions such as the rhizome of the multiple medicinal plants such as Radix Polygoni Multiflori, Folium Symplocoris Caudatae, Folium Sennae or pod, have (1) anti-tumor activity: black to mice
Melanoma, ehrlich carcinoma, hepatocarcinoma, breast carcinoma, P388 leukaemia have certain inhibitory action；(2) antibacterial activity: right
Staphylococcus, streptococcus, diphtheria corynebacterium, bacillus subtilis, Salmonella paratyphi, dysentery bacterium etc. all have inhibitory action；(3) immunity presses down
Make and use: organism antibody can be suppressed to produce, suppress carbon clearance ability, alleviate the weight of immune organ, reduce leukocyte count；
(4) diuresis: sodium in urine, potassium concentration can be made to raise, promotes ureteral peristalsis, increases urine volume；(5) discharge function: big
Yellow acid itself is without discharge function, and its intestinal flora converted product chrysophanic acid anthrone has Purgative activity, it is possible to reduce colon to sodium and chlorine
The absorption of ion, increases potassium ion secretion；(6) treatment diabetic nephropathy: can improve abnormal carbohydrate metabolism, reverses insulin and supports
Anti-, effectively prevent diabetic nephropathy, and safety is preferable.
At present, application chrysophanic acid have not been reported as active ingredient preventing/treating depression.
Summary of the invention
Based on inventor chancing on, the present invention provides a kind of salt using chrysophanic acid or chrysophanic acid as active ingredient
Antidepressants, this medicine has the advantages such as antidepressant effect is notable, dosage is few, rapid-action.
The technical scheme that the present invention is claimed is as follows:
The medicine of a kind of depression, it is characterised in that its antidepressant active ingredient is the salt of chrysophanic acid or chrysophanic acid.
The pharmaceutical composition of a kind of depression, it is characterised in that its antidepressant composition and effectiveness includes chrysophanic acid or Radix Et Rhizoma Rhei
The salt of acid.
The medicine of a kind of Fast Anti depression, it is characterised in that its active ingredient is the salt of chrysophanic acid or chrysophanic acid.
The medicine of described Fast Anti depression, it is characterised in that its effective dose is that every kg body weight 0.01-100mg is big
Yellow acid or the salt of every considerable amount of chrysophanic acid of kg body weight 0.01-100mg chrysophanic acid；Antidepressant can be produced in being administered latter 60 minutes
Effect.
Arbitrary described medicine, it is characterised in that after also including simultaneously using with chrysophanic acid, treatment depression is had actively
Effect ingredient and/or make the stability-enhanced pharmaceutically acceptable composition of chrysophanic acid.
Arbitrary described medicine, it is characterised in that also include acceptable auxiliary element on pharmacopedics.
Arbitrary described medicine, it is characterised in that its dosage form be powder, granule, tablet, capsule, pill, solution,
Suspension or injection.
Chrysophanic acid purposes in preparing anti-depression drug, it is characterised in that with the salt of chrysophanic acid or chrysophanic acid as medicine
Effect composition prepares anti-depression drug.
In described purposes, the effective dose of described anti-depression drug is every kg body weight 0.01-100mg chrysophanic acid or every
The salt of the considerable amount of chrysophanic acid of kg body weight 0.01-100mg chrysophanic acid；Antidepressant effect can be produced in being administered latter 60 minutes.
A kind of method for the treatment of/prevention of depression, it is characterised in that make experimenter take in claim 1～7 arbitrary described
Medicine.
Dosage is: provide 0.01-100mg chrysophanic acid per kg body weight per day, or 0.01-100mg chrysophanic acid is suitable
The salt of the chrysophanic acid of amount.
The research of the present invention finds, in mammal mouse experiment, chrysophanic acid has effect of Fast Anti depression, and
More more effective than conventional antidepressant agents imipramine.
Mouse model tail-suspention test finds, the high dose group (10mg/kg) of chrysophanic acid and 1%DMSO matched group
Compare, within 60 minutes, just can substantially shorten the mouse tail suspension dead time in injection.The low dose group dead time also shows that reduction becomes
Gesture；And imipramine is compared the dead time and is the most substantially shortened with normal saline after injecting 60 minutes.Result shows the big of high dose
Yellow acid gets final product onset in a short period of time, and effect is extremely notable, the depressive symptom that can cause anti-mouse because forcing outstanding tail.
And chrysophanic acid is in the case of dosage is less than imipramine, earlier demonstrates antidepressant effect than imipramine.Embodiment 1 is listed
Mice is respectively organized after 60 minutes in observed 6 minutes in injection, latter 4 minutes interior accumulative dead times, result such as Fig. 2
Shown in.
Further, in forced swim test, dead time during chrysophanic acid dosage 10mg/kg and imipramine positive controls
(15mg/kg) dead time is quite (as shown in Figure 3).Comparing with imipramine, chrysophanic acid effective dose is lower.It is indicated above that
Chrysophanic acid has stronger antidepressant effect to model mice, has the potentiality as Fast Anti antidepressant agents.
The effective ingredient chrysophanic acid of antidepressant drug of the present invention, its chemical structural formula as it is shown in figure 1, also have antitumor,
Antibacterial, antiinflammatory, effectively preventing the effect such as diabetes, nephropathy, safety is good.Therefore, chrysophanic acid is expected to become quick, Effective Anti
Depressed new drug.
Experimental data based on the present invention, the present invention be claimed the anti-depression drug with chrysophanic acid as active ingredient or
Pharmaceutical composition, the most any medicine or fast identifying with chrysophanic acid as active ingredient and identify that its indication comprises depression
The medicine of speed depression, or the pharmaceutical composition with chrysophanic acid as composition and effectiveness to be all that the patent that is claimed of the present invention is anti-press down
Strongly fragrant disease drug.The present invention is also claimed chrysophanic acid purposes in preparing anti-depression drug, any with chrysophanic acid as drug effect
Composition prepares the production row for the purpose of profit of anti-depression drug, Fast Anti antidepressant agents, antidepressant compositions
For broadly falling into the scope that the present invention is claimed.
The medicament screening experiment that the present invention uses is: forced swim test and Tail suspension test, is that conventional two kind move
Thing behavioral despair depression model is tested, and can preferably ensure the reliability of the selection result.
Mouse forced swimming test has been used for the screening of a lot of antidepressant drug.And great majority have clinical treatment effect
Antidepressants are also proved in forced swim test and can effectively reduce the dead time.What is called is motionless refers to that " animal stops in water
Only struggling, or in floating state, only expose nostril and keep breathing, the most tiny limb motion, to keep head to float over water
Face ".Give to intend the medicine of screening before the test.Swimming under obsessive state due to animal makes animal can not escape from adverse circumstances,
Cause animal behavior desperate.This kind of model method simplicity, reliably, is widely used in screening and the evaluation of antidepressant medicament.
Tail suspension test is that mice no longer struggles under outstanding shape of tail state, presents the motionless state of distinctive peace and quiet, antidepressant
Medicine can substantially shorten the persistent period of motionless state.During test, mouse tail fixed, hang by the feet.Do not make mouse tail distortion folding
Folded.The meter record dead time.Stationarity indices is: " animal all limbs in addition to breathing are the most motionless ".Tail-suspention test is to various antidepressants
Medicine is the most very sensitive, and avoids temperature and the handicapped interference of animal movement in swimming test, thus by some Mus kinds
During screening antidepressant drug, can effectively verify and supplement the result of forced swim test.
The chrysophanic acid purposes in preparing anti-depression drug that the present invention provides, prepared obtained by antidepressant
Thing, can the general knowledge of technical staff based on pharmaceutical field and add the auxiliary element that do not affects medicine effect, such as carrier, figuration
Agent, correctives etc..Owing to this medicine all can be taken effect by the mode such as oral, injection, subcutaneous embedding, therefore, dosage form can be many
Sample, include but not limited to powder, granule, tablet, capsule, pill, solution, suspension or injection.
The anti-depression drug that the present invention provides can also be mixed with other with chrysophanic acid or derivatives thereof with the use of right
Treatment depression has the ingredient of positive role.
Those skilled in the art can add makes the stability-enhanced stabilizer of chrysophanic acid, as long as not affecting sending out of drug effect
Waving, the anti-depression drug of gained is all in the scope of protection of present invention.
Anti-depression drug provided by the present invention, described depression includes prevention and two stages for the treatment of.
The consumption of described anti-depression drug is: provide 0.01-100mg chrysophanic acid, or 0.01-per kg body weight per day
The salt of the considerable amount of chrysophanic acid of 100mg chrysophanic acid.
The administering mode of described anti-depression drug is for being administered orally, instil or injecting；Administration object is mammal, the described food in one's mouth
Breast animal includes people.
Owing in classical depressed animal model, the shortening of animal dead time is likely due to the central excitatory work of medicine
With caused, therefore the present invention has carried out mice Open field activity (Open field test) the most simultaneously, to check the autonomous of mice
Activeness, it is to avoid the interference of central stimulants.Result shows, compared with matched group, high concentration chrysophanic acid is to mice autonomic activities
Do not make significant difference, therefore the probability of false positive results can be got rid of, it was demonstrated that chrysophanic acid has significant antidepressant effect really.
The pharmaceutical composition that the present invention is claimed, refers to that manually compound is blended in one with two kinds and above composition and effectiveness
Act the medicine prepared.The Cordyceps applied for and announce before the chrysophanic acid of the most this compositions such as present invention employing and applicant
The antidepressant compositions of the combinations of substances such as element, lentinan, astaxanthin.Be different from comprise certain active ingredient but
It it is the natural plants of complicated component.
Accompanying drawing explanation
Fig. 1. the chemical structural formula of chrysophanic acid.
Fig. 2. the chrysophanic acid impact on Tail suspension test,
Wherein, vertical coordinate: tail-suspention test mice dead time (s)；Abscissa: be from left to right followed successively by: 1%DMSO compares
Group, chrysophanic acid low dose group (5mg/kg), chrysophanic acid high dose group (10mg/kg), saline control group, the imipramine positive is right
According to group (15mg/kg).
Result: CD1 male mice is after the chrysophanic acid lumbar injection 60 minutes of various dose, and high dose group is in mouse tail suspension
Experiment demonstrates extremely significantly antidepressant effect (every treated animal N=24, t check * p ＜ 0.05, * * p ＜ 0.01).
Fig. 3. the chrysophanic acid impact on mouse forced swimming test,
Wherein, vertical coordinate: forced swim test mice dead time (s), abscissa: be from left to right followed successively by: 1%DMSO
Matched group, chrysophanic acid low dose group (5mg/kg), chrysophanic acid high dose group (10mg/kg), saline control group, imipramine sun
Property matched group (15mg/kg).
Result: CD1 male mice is after the chrysophanic acid lumbar injection five days of various dose, in mouse forced swimming test
Demonstrate notable antidepressant effect (every treated animal N=8-10, t check * p ＜ 0.05, * * p ＜ 0.01).
Detailed description of the invention
Below by way of specific embodiment, the present invention is described in detail, it is to be understood that following embodiment is only used as
Explain and explanation, limit the scope of the present invention the most in any form.
In following embodiment, not specified biological chemical reagent is this area conventional reagent, can be according to this
Field conventional method is prepared and is obtained or commercially available, and specification is the pure level of laboratory.
The impact on Tail suspension test of embodiment 1. chrysophanic acid
Laboratory animal:
CD1 kind mice, male, weight 30-40 gram, Beijing Vital River Experimental Animals Technology Co., Ltd. provide, permitted
Can the number of card: SCXK (capital) 2012-0001.Test the last week by animal sub-cage rearing, light and shade cycle 12h/12h, room temperature 20～22
DEG C, freely, feedstuff is provided drinking water by Inst. of Genetics and Development Biology, CAS's Experimental Animal Center.
Experimental drug:
Chrysophanic acid, purchased from Shanghai Institute Center of Standardization for Traditional Chinese Medicine, article No. 04-2008.
Imipramine hydrochloride (Imipramine hydrochloride) is Sigma Products, article No. I7379, lot number
O56K1380。
Experiment equipment:
Cross bar；Adhesive plaster；Sumsung Intelli-200m DV (Samsung of Korea S)；The multi-functional meter of JUNSO
Time device.
Experimental procedure:
Male CD1 mice is raised one week through adaptability, is divided into 5 groups, often group 24.It is respectively
1%DMSO matched group (DMSO is dissolved in normal saline),
Chrysophanic acid low dose group (5mg/kg is dissolved in 1%DMSO),
Chrysophanic acid high dose group (10mg/kg is dissolved in 1%DMSO),
Tradition antidepressant drug imipramine positive controls (15mg/kg imipramine, physiological saline solution),
Saline control group.
0.3ml/30g body weight intraperitoneal injection is pressed during the morning 10.
After injecting 60 minutes, often group randomly selects 12 mices and carries out tail-suspention test；
After injecting 90 minutes, carry out tail-suspention test to often organizing remaining 12 mices；
During Tail suspension test, with adhesive plaster, mouse tail is being bonded on a horizontal cross bar away from tail point 2 centimeters, is making animal
Become reversal of the natural order of things state, about 15 centimetres from desktop of its head.Observe 6 minutes, record latter 4 minutes interior accumulative dead times.Fixed finger
It is designated as: animal all limbs in addition to breathing are the most motionless.
Experimental result:
Statistical method: experimental result mean value ± SE represents, two sample mean compare to be checked with t.
Chrysophanic acid high dose group mice 60 minutes depressive symptoms after injection start to alleviate, and i.e. activity is relative to blank
Organize more and more frequent, hence it is evident that shortening the dead time.And imipramine positive controls is after injection in 60 minutes, activity and life
Reason saline control group indifference, until after 60 minutes, it is relatively frequently movable just to begin with.
Imipramine positive controls is compared with the mice of normal saline group, and after injecting 60 minutes, the dead time the most substantially contracts
Short, start after injecting 90 minutes substantially to shorten the outstanding tail dead time.
Inject observed result after 60 minutes, as in figure 2 it is shown, the dead time of chrysophanic acid high dose group with 1%DMSO pair
Compare according to group and be reduced to 20.33 ± 5.52s (p ＜ 0.01) by 102.29 ± 12.37s, shorten 80.1%.Chrysophanic acid low dosage
The mice dead time of group also shows that reduction trend.
It is indicated above that the chrysophanic acid of high dose gets final product onset in a short period of time, and effect is extremely notable, can resist little
The depressive symptom that Mus is caused because forcing outstanding tail.
The impact on animal depression model forced swim test of embodiment 2. chrysophanic acid
Laboratory animal:
CD1 kind mice, male, Beijing Vital River Experimental Animals Technology Co., Ltd. provide, credit number: SCXK
(capital) 2012-0001.Experiment the last week by animal sub-cage rearing, light and shade cycle 12h/12h, room temperature 20～22 DEG C, drinking water freely,
Feedstuff is provided by Inst. of Genetics and Development Biology, CAS's Experimental Animal Center.
Experimental agents:
Chrysophanic acid, purchased from Shanghai Institute Center of Standardization for Traditional Chinese Medicine, article No. 04-2008.
Imipramine hydrochloride (Imipramine hydrochloride) is Sigma Products, article No. I7379, lot number
O56K1380。
Test apparatus:
Glass cylinder (high 40cm, diameter 14cm)；The open case of mice (long and wide respectively 50cm, high 40cm, bottom 16 etc.
Point)；Thermometer；JUNSO Multifunctional time-meter.
Experimental procedure:
Animal pharmaceuticals is injected:
CD1 male mice, 7 weeks ages, weight 30-40 gram, adapt to environment and after one week, start experiment.Animal is randomly divided into 5
Group, often group 8-10 is only, respectively 1%DMSO matched group (DMSO is dissolved in normal saline), chrysophanic acid low dose group (5mg/kg, molten
In 1%DMSO), chrysophanic acid high dose group (10mg/kg is dissolved in 1%DMSO), tradition antidepressant drug imipramine positive controls
(15mg/kg imipramine, physiological saline solution), saline control group.Every morning 10 starts lumbar injection, and injection volume is
0.3 milliliter/30 grams, every day lumbar injection once, after injecting five days start forced swim test.
Forced swim test:
(40cm height × 14cm diameter), depth of water 25cm, water it is placed vertically in plexiglass cylinder by single for each group of CD1 Mus
Temperature 21-23 DEG C.Each administration group and matched group are recorded a video 6 minutes, and respectively group mice was latter 4 minutes interior accumulative dead times.No
The dynamic time judges: mice swims in the water surface, does not make great efforts to climb out of cylinder, only does some and its head must be kept in the action of the water surface.
Statistical analysis technique:
Experimental result mean value ± SE represents, two sample mean compare to be checked with t.
Result is as it is shown on figure 3, compare with 1%DMSO matched group, and chrysophanic acid high dose group mouse forced swimming test 4 minutes is interior
Dead time significantly shortens, and has certain dose dependent, the dead time and 1% during chrysophanic acid dosage 10mg/kg
DMSO matched group is compared, 98.86 ± 19.67s be reduced to 48.44 ± 13.69s (p ＜ 0.05), shorten 51%；And tradition
Antidepressants imipramine is compared, and effective dose is lower.It is indicated above that chrysophanic acid has stronger antidepressant effect.
Embodiment 3. mice Open field activity
Owing in classical depressed animal model, the shortening of animal dead time is likely due to the central excitatory work of medicine
With causing, so We conducted mice Open field activity to check the central excitatory of chrysophanic acid.
Experimental result shows, total distance that mice moves in open case for 1 hour is after chrysophanic acid high dose processes
(66.41+5.33m) compared with matched group (56.40 ± 3.53m), without significant change (Anova, p ＞ 0.05, N=8-10), therefore
Can get rid of its probability causing manic state, therefore, chrysophanic acid has significant antidepressant effect really.
Embodiment 4 pharmaceutical composition effect experiment
Repeat the experiment of embodiment 1-3, simply Experimental agents be rubescensine A with cordycepin, lentinan, astaxanthin,
The 1:1 combination of the formerly disclosed antidepressant effective ingredient such as Ganodenic acid A.
Experimental result display Tail suspension test, forced swim test, Open field activity result show identical with embodiment 1-3
Trend and significance.
Claims (10)
1. the medicine of a depression, it is characterised in that its antidepressant active ingredient is the salt of chrysophanic acid or chrysophanic acid.
2. the pharmaceutical composition of a depression, it is characterised in that its antidepressant composition and effectiveness includes chrysophanic acid or chrysophanic acid
Salt.
3. the medicine of a Fast Anti depression, it is characterised in that its active ingredient is the salt of chrysophanic acid or chrysophanic acid.
The medicine of Fast Anti depression the most according to claim 3, it is characterised in that its effective dose is every kg body weight
0.01-100mg chrysophanic acid or the salt of every considerable amount of chrysophanic acid of kg body weight 0.01-100mg chrysophanic acid；It is administered in latter 60 minutes
Antidepressant effect can be produced.
5. according to the arbitrary described medicine of Claims 1 to 4, it is characterised in that to controlling simultaneously after also including using with chrysophanic acid
Treat depression have the ingredient of positive role and/or make the stability-enhanced pharmaceutically acceptable composition of chrysophanic acid.
6. according to the arbitrary described medicine of Claims 1 to 4, it is characterised in that also include acceptable on pharmacopedics auxiliary into
Point.
7. according to the arbitrary described medicine of Claims 1 to 4, it is characterised in that its dosage form is powder, granule, tablet, capsule
Agent, pill, solution, suspension or injection.
8. chrysophanic acid purposes in preparing anti-depression drug, it is characterised in that with the salt of chrysophanic acid or chrysophanic acid as drug effect
Composition prepares anti-depression drug.
Purposes the most according to claim 8, the effective dose of described anti-depression drug is every kg body weight 0.01-
100mg chrysophanic acid or the salt of every considerable amount of chrysophanic acid of kg body weight 0.01-100mg chrysophanic acid；Can produce in being administered latter 60 minutes
Raw antidepressant effect.
10. the method for a treatment/prevention of depression, it is characterised in that make experimenter take in claim 1～7 arbitrary described
Medicine；
Dosage is: provide 0.01-100mg chrysophanic acid per kg body weight per day, or 0.01-100mg chrysophanic acid is considerable amount of
The salt of chrysophanic acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510671062 | 2015-10-16 | ||
| CN201510671062X | 2015-10-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106038522A true CN106038522A (en) | 2016-10-26 |
| CN106038522B CN106038522B (en) | 2019-08-16 |
Family
ID=56394169
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610158023.4A Pending CN105770357A (en) | 2015-10-16 | 2016-03-18 | Use of alliin in preparation of antidepressants |
| CN201610158225.9A Active CN105832724B (en) | 2015-10-16 | 2016-03-18 | Purposes of the indanol in anti-depression drug is prepared |
| CN201610494641.6A Active CN106038522B (en) | 2015-10-16 | 2016-06-28 | Rhein is preparing the purposes in anti-depression drug |
| CN201610695266.1A Active CN106176748B (en) | 2015-10-16 | 2016-08-19 | Norisoboldine is preparing the purposes in anti-depression drug |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610158023.4A Pending CN105770357A (en) | 2015-10-16 | 2016-03-18 | Use of alliin in preparation of antidepressants |
| CN201610158225.9A Active CN105832724B (en) | 2015-10-16 | 2016-03-18 | Purposes of the indanol in anti-depression drug is prepared |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610695266.1A Active CN106176748B (en) | 2015-10-16 | 2016-08-19 | Norisoboldine is preparing the purposes in anti-depression drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (4) | CN105770357A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112168968A (en) * | 2020-09-25 | 2021-01-05 | 中山大学附属第八医院（深圳福田） | Application of FTO inhibitor in preparation of product for preventing and treating breast cancer |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110251559A (en) * | 2019-07-29 | 2019-09-20 | 西南交通大学 | A kind of application of root of three-nerved spicebush tuber extract in preparation antidepressant |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440747A (en) * | 2003-03-31 | 2003-09-10 | 中国人民解放军肾脏病研究所 | Application of chrysophanic acid and chrysophanate in preparing obesity treating medicine |
| CN102060809A (en) * | 2009-05-01 | 2011-05-18 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Rhein derivatives and preparation and application thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5962566A (en) * | 1982-10-01 | 1984-04-10 | Tanabe Seiyaku Co Ltd | Preparation of hydroxyindole |
| US5212195A (en) * | 1992-05-13 | 1993-05-18 | Syntex (U.S.A.) Inc. | Substituted indole antagonists derivatives which are angiotensin II |
| DE10253426B4 (en) * | 2002-11-15 | 2005-09-22 | Elbion Ag | Novel hydroxyindoles, their use as inhibitors of phosphodiesterase 4 and methods for their preparation |
| CN1269527C (en) * | 2003-06-03 | 2006-08-16 | 陈坚 | Compound alliin powder injection |
| CN100453080C (en) * | 2005-09-28 | 2009-01-21 | 上海中医药大学 | Lindera root alkaloid, its preparation method and application in medicine preparation |
| FR2918570B1 (en) * | 2007-07-09 | 2012-10-05 | Engelhard Lyon | DIGLYCATION OF AGEs. |
| CN101327289B (en) * | 2008-07-31 | 2011-06-15 | 倪健 | Novel uses of day lily and day lily total flavones |
| CN101375850B (en) * | 2008-10-07 | 2010-08-25 | 中国药科大学 | Application of norisoboldine in preparing medicament for treating autoimmune disease |
-
2016
- 2016-03-18 CN CN201610158023.4A patent/CN105770357A/en active Pending
- 2016-03-18 CN CN201610158225.9A patent/CN105832724B/en active Active
- 2016-06-28 CN CN201610494641.6A patent/CN106038522B/en active Active
- 2016-08-19 CN CN201610695266.1A patent/CN106176748B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1440747A (en) * | 2003-03-31 | 2003-09-10 | 中国人民解放军肾脏病研究所 | Application of chrysophanic acid and chrysophanate in preparing obesity treating medicine |
| CN102060809A (en) * | 2009-05-01 | 2011-05-18 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Rhein derivatives and preparation and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| RAZ YIRMIYA 等: "Depression as a Microglial Disease", 《TRENDS IN NEUROSCIENCES》 * |
| 刘德祥: "氟西汀抑制脂多糖诱导的小胶质细胞炎症介质释放及其机制的研究", 《中国博士论文全文数据库》 * |
| 景浩然 等: "大黄酸对内毒素激活小胶质细胞的影响", 《天津中医药大学学报》 * |
| 赵一洁 等: "大黄酸肠溶缓释微丸的制备及体外释放度考察", 《中成药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112168968A (en) * | 2020-09-25 | 2021-01-05 | 中山大学附属第八医院（深圳福田） | Application of FTO inhibitor in preparation of product for preventing and treating breast cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106038522B (en) | 2019-08-16 |
| CN105832724B (en) | 2018-07-03 |
| CN105770357A (en) | 2016-07-20 |
| CN106176748B (en) | 2019-01-18 |
| CN105832724A (en) | 2016-08-10 |
| CN106176748A (en) | 2016-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101735151B1 (en) | Anti-fatigue composition, formulation and use thereof | |
| CN103432184B (en) | Application of great burdock fruit extract in drug production or foods | |
| CN102274227B (en) | Application of tetrandrine in preparation of drug for prevention and/or treatment of depression | |
| CN103860530A (en) | Application of astaxanthin as antidepression medicine | |
| CN106038534A (en) | Application of oridonin in preparation of anti-depression medicines | |
| CN106038522A (en) | Application of rhein in preparation of anti-depression medicines | |
| CN104223073B (en) | A kind of food, health products or pharmaceutical composition of sleeping | |
| CN103705774A (en) | Compound composition with effect of treating depression as well as preparation method and application thereof | |
| CN103127163B (en) | Anxiety-relieving, depression-relieving, mood-soothing, and mental-stress-reducing composite, and preparation method and purpose thereof | |
| CN106265713B (en) | Purposes of the cordycepin in the drug for preparing depression and its quick anti-depression drug being prepared | |
| CN103860578A (en) | Use of lentinan as antidepressant drug | |
| CN106822098A (en) | Application of the arctigenin in depression product is prepared | |
| CN105919991B (en) | Application of the euparin in preparation medicament for treatment of depression | |
| CN103800341B (en) | The combination medicine of anti-curing oncoma | |
| CN114469967B (en) | Application of atractyloside A and derivatives thereof in preparation of anxiolytic and antidepressant drugs | |
| CN105816460B (en) | A kind of pharmaceutical composition treating postpartum depression | |
| EP3466414B1 (en) | Use of nootkatone | |
| CN101411700B (en) | Use of 5,7,4'-trihydroxy flavanone or derivative thereof for analgesia | |
| CN101732248B (en) | Metoprolol tartrate injection and preparation method thereof | |
| CN104138557A (en) | Chinese herbal medicine compound preparation for preventing and treating senile dementia | |
| CN106491524B (en) | A kind of Betahistine Hydrochloride oral liquid and preparation method thereof and new application | |
| CN112618524A (en) | ASBDV composition for improving sleep disorder and preparation and application thereof | |
| Hassan et al. | Emergency Available Drugs in Markets to Treat COVID-19 | |
| CN105395680B (en) | It is a kind of to treat neurasthenic Chinese medicine composition and its preparation method and application | |
| CN101310715A (en) | Tanshinol for preparing the medicine for preventing and treating depression and sodium salt thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220620 Address after: 102218 304, 87 / F, gongyuanli, East 1st District, Tiantongyuan, Changping District, Beijing Patentee after: Luo Yongqiang Address before: Room b273, Chuangxin building, No. 29, shengshengyuan Road, Changping District, Beijing 102206 Patentee before: BEIJING GRAGEN BIOTECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20231206 Address after: Floor 3, Building 402, Zone 1, Tiantong Dongyuan, Dongxiaokou Town, Changping District, Beijing, 102218 Patentee after: Beijing Yasheng Bohou Biotechnology Development Center Address before: 102218 304, 87 / F, gongyuanli, East 1st District, Tiantongyuan, Changping District, Beijing Patentee before: Luo Yongqiang |
|
| TR01 | Transfer of patent right |