CN107137391A - Purposes of the dihydromyricetin in terms of the medicine for the treatment of depression is prepared - Google Patents

Purposes of the dihydromyricetin in terms of the medicine for the treatment of depression is prepared Download PDF

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Publication number
CN107137391A
CN107137391A CN201710370269.2A CN201710370269A CN107137391A CN 107137391 A CN107137391 A CN 107137391A CN 201710370269 A CN201710370269 A CN 201710370269A CN 107137391 A CN107137391 A CN 107137391A
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group
cycloalkyloxies
hydroxyl
medicine
depression
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镇学初
任兆翔
颜鹏举
钱勇
谢天培
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SHANGHAI NATURE STANDARD BIOTECHNOLOGY CO Ltd
Suzhou University
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SHANGHAI NATURE STANDARD BIOTECHNOLOGY CO Ltd
Suzhou University
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    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • 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
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Nutrition Science (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to dihydromyricetin prepare treatment depression medicine in terms of purposes, should comprising dihydromyricetin medicine after application can quick acting, so as to realize the rapid recovery to depression and treatment.

Description

Purposes of the dihydromyricetin in terms of the medicine for the treatment of depression is prepared
Technical field
The present invention relates to pharmaceutical technology field, especially psychotic disorder pharmaceutical technology field, more particularly to dihydro poplar Purposes of the syphilis in terms of the medicine for the treatment of depression is prepared.
Background technology
Depressive symptom is a kind of clinical symptoms of mood disorder, and depression is so that notable and lasting mental state is low, thinking Slow, Cognitive function damage, bulesis decline and the class mood disorder that somatization is main clinical characteristics.WHO is newest The global depression of statistics and pernicious mental state person's illness rate predict that the year two thousand twenty depression will turn into global second doctor up to 12.8% Treat illness.Depression not only makes patient health suffer damage, and quality of life declines, and causes very big burden to family, society, Have become a serious society and medical care problem.Therefore, the research of antidepressant has obtained the common concern of people.Mesh The treatment method of preceding depression has drug therapy, electro-shock therapy (ECT), transcranial magnetic treatment (TMS), vagal stimulation Treatment (VNS), sleep deprivation treatment, light exposure treatment, Psychosurgery treatment and psychotherapy etc..Wherein, drug therapy is One Main Means for the treatment of depression, have data to show that about 2/3 patient can obtain different curative effects by drug therapy.It is anti- Depressant drug thing is broadly divided into tricyclic antidepressant and non-selective monoamine oxidase inhibitor, selectivity 5-HT reuptakes suppress Agent, norepinephrine and specificity 5-HT antidepressants, 5-HT and NRI.But, tradition Antidepressant onset time it is slow (about 2~3 weeks), curative effect is weak, it is impossible to quickly alleviate conamen.Therefore, it is badly in need of compeling Cut the antidepressants for sending new quick acting.
Dihydromyricetin also known as Ampeloptin, ampelopsin, are flavanone alcohols compound, be present in Vitaceae, In the plants such as Myruca ceas, Cuculidae, wherein, the content of dihydromyricetin is up to 25% in vitaceae vine tea particularly especially Left and right.For a long time, health protection tea is made in the young young stem and leaf of vine tea by China's Zhuang and Yao nationality people, for treat cat fever, The diseases such as abscess of throat, icteric hepatitis, the title for having " refreshing tea ".In recent years pharmacological evaluation prove dihydromyricetin have analgesia, The multiple efficacies such as cough-relieving, broad-spectrum antiseptic, hypoglycemic, reducing blood lipid, anti-oxidant, but its effect to mental disorder does not appear in the newspapers Road.
The content of the invention
It is an object of the invention to provide it is a kind of can quick acting antidepressants.Specifically, the invention provides dihydro Purposes of the myricetin in terms of the medicine for the treatment of depression is prepared.
The first aspect of the present invention there is provided a kind of compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt Or the purposes of ester, the medicine for preparing prevention or treatment depression,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
In another preference, the number of the hexa-atomic ring substituents C1-C6 alkyl is 2.
In another preference, 2 substituent C1-C6 alkyl are incorporated on same carbon atom on the hexatomic ring.
In another preference, R1、R2、R3、R4、R5And R6Middle 0-6 are hydroxyl.
In another preference, R1、R2、R3、R4、R5And R6Middle 0-6 are acetoxyl group.
In another preference, the compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester be selected from The following group：
In another preference, " derivative " refers to compoundAcetylation production Thing, glycosylation product or esterification products.
In another preference, " pharmaceutically acceptable salt " refers to compound Sodium salt and/or sylvite.
In another preference, the depression is the depression being selected from the group：Mild depression, moderate depressive patients, again Spend depression.
In another preference, the medicine is included：
Component i)：Compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester；With
Component ii)：Pharmaceutically acceptable carrier.
In another preference, component i) mass content is 0.01-99.99wt% in the medicine, preferably 0.1- 99wt%, more preferably 1-90wt%.
In another preference, the medicine is to the prevention or treatment of depression by improving intracerebral brain-derived neurotrophy Factor B DNF expression is realized.
The second aspect of the present invention is included there is provided a kind of medicine for being used to preventing or treating depression, the medicine：
Component i)：Compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester, as pharmaceutical activity into Point；With
Component ii)：Pharmaceutically acceptable carrier；
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces..
In another preference, the formulation of the medicine is selected from the group：Tablet, capsule, granule, injection.
In another preference, the medicine also includes the second active constituents of medicine, and second active constituents of medicine is not Component i) is same as, and second active constituents of medicine is used to prevent or treat depression.
In another preference, second active constituents of medicine is animals and plants extract or Chinese medicinal powder.
There is provided a kind of health products or beverage for being used to preventing or treating depression, the guarantor for the third aspect of the present invention Strong product or the beverage packets containing compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
There is provided a kind of side for the expression for improving intracerebral BDNF BDNF for the fourth aspect of the present invention Method, by compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester be applied to subject,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
In another preference, the subject behaves or non-human mammal (such as rat, mouse).
The fifth aspect of the present invention there is provided it is a kind of prevent or treatment depression method, by compound of formula I or its spread out Biological or its pharmaceutically acceptable salt or ester are applied to subject,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
In another preference, compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester amount of application For 5-100mg/kg, preferably 8-50mg/kg, more preferably 10-30mg/kg.
In another preference, compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester administration side Formula is selected from the group：Intraperitoneal injection, oral, hypodermic injection.
In another preference, compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester administration time Number is daily 1-3 times, is preferably once a day.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and have in below (eg embodiment) It can be combined with each other between each technical characteristic of body description, so as to constitute new or preferred technical scheme.As space is limited, exist This no longer tires out one by one states.
Brief description of the drawings
Fig. 1 is effect of the dihydromyricetin to acute depression in embodiment 1, wherein, figure A was successive administration after 3 days The result of tail-suspention test, figure B is the successive administration result that forced swimming is tested after 3 days.
Fig. 2 be embodiment 2 in dihydromyricetin chronic unpredictability is gently stimulated (CUMS, it is aftermentioned all be referred to as mould Type group) induction depression effect, wherein, figure A is the syrup preference that modeling eight weeks and then successive administration are tested after seven days As a result, figure B is the tail-suspention test result of modeling eight weeks and then successive administration test after seven days, and figure C is modeling eight weeks and then connected The forced swimming result that continuous administration is tested after seven days.
Fig. 3 gently stimulates modeling for chronic unpredictability in embodiment 3, Western Blot after being then administered seven days GAP-associated protein GAP (p-CREB, CREB, p-ERK1/2, t-ERK1/2, BDNF, GSK3 β, pS9-GSK3 β) contains in technical Analysis hippocampus Measure the result of change.
Embodiment
The present inventor's in-depth study by long-term, it has unexpectedly been found that dihydromyricetin can be used for preparing treatment depression Medicine, and should medicine comprising dihydromyricetin after application can quick acting, so as to realize to the quick slow of depression Solution and treatment.On this basis, inventor completes the present invention.
Active component
In the present invention be used for prevent or treat depression medicine active component for compound of formula I, or derivatives thereof or Its pharmaceutically acceptable salt or ester,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
Typically, the compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester be selected from the group：
Intracerebral BDNF (BDNF)
BDNF is BDNF, is a kind of protein synthesized in intracerebral, it is widely distributed in maincenter In nervous system, during development of central nervous system, survival to neuron, break up, growing plays an important role, and It can prevent that neuronal damage is dead, improve neuron pathological state, promote to be damaged the biological effects such as neuron regeneration and differentiation, And be also that the neuron of ripe maincenter and peripheral nervous system is survived and normal physiological function institute is required.Neuroimaging Learn measurement and find that Brain of Patients with Depression cortex of temporal lobe particularly hippocampus position density declines, the dendron of neuron is reduced and neuron Necrosis.And BDNF can prevent that neuronal damage is dead, improve neuron pathological state, promoting to be damaged neuron regeneration and divide Change, so as to reach the depressed purpose for the treatment of.
Purposes
Specifically, the invention provides a kind of compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester Purposes, for prepare prevention or treatment depression medicine,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 Alkoxy, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring, and the hexatomic ring quilt with adjacent four carbon atom formation C1-C6 alkyl replaces.
Present invention also offers a kind of medicine for being used to preventing or treating depression, the medicine is included：
Component i)：Compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester, as pharmaceutical activity into Point；With
Component ii)：Pharmaceutically acceptable carrier.
Present invention also offers a kind of health products or beverage for being used to preventing or treating depression, the health products or described Beverage packets containing compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester.
Present invention also offers a kind of method for the expression for improving intracerebral BDNF BDNF, by Formulas I Compound, or derivatives thereof or its pharmaceutically acceptable salt or ester be applied to subject.
Present invention also offers it is a kind of prevent or treatment depression method, by compound of formula I, or derivatives thereof or its Pharmaceutically acceptable salt or ester are applied to subject.
Compared with prior art, the present invention has following major advantage：
(1) medicine comprising dihydromyricetin can quick acting after application so that in a short time (such as it is chronic not Predictability is gently stimulated on modeling (CUMS) mouse, and traditional antidepressant Venlafaxine (10mg/kg) is to model group Mice behavior improves onset time about at three weeks or so, and dihydromyricetin only needs to about week age and can significantly changed The Behavioral feature of kind model group mouse) improve depressive symptom, and then the treatment to depression is realized, it is a kind of new anti-suppression Strongly fragrant medicine；
(2) China's dihydromyricetin aboundresources, it is present in the plant of many, especially with containing in ampelopsis Amount occupies high.In addition, dihydromyricetin also has the advantages that bioactivity is strong, toxicity is relatively low.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention Rather than limitation the scope of the present invention.The experimental method of unreceipted actual conditions in the following example, generally according to conventional strip Part or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise percentage and number are calculated by weight.In the present invention In, all intraperitoneal injections of administering mode of mouse, once a day.
Unless otherwise defined, all specialties used in text known to scientific words and one skilled in the art with anticipating Justice is identical.In addition, any method similar or impartial to described content and material all can be applied in the inventive method.Wen Zhong Described preferable implementation only presents a demonstration with material to be used.
Effect of the dihydromyricetin of embodiment 1 (DHM) to acute depression
It is 6-8 week by week old, body weight is that 25 ± 2g C57 mouse are randomly divided into five groups, including：Physiological saline group, dihydro poplar Syphilis 5mg/kg groups, dihydromyricetin 10mg/kg groups, dihydromyricetin 20mg/kg groups (DHM DMSO dissolve) and Venlafaxine (Venlafaxine is a kind of depressed medicine of the treatment listed to 10mg/kg groups, and its structural formula is ).Direct successive administration three days, then does tail-suspention test and forced swimming test, the result drawn is as shown in figure 1, wherein Figure 1A For tail-suspention test result, Figure 1B is forced swim test result.
The result of administration three days shows：Dihydromyricetin 10mg/kg, dihydromyricetin 20mg/kg and Venlafaxine 10mg/ Kg groups have significant difference compared to physiological saline group, illustrate that dihydromyricetin has certain treatment to make to acute depression With.
The dihydromyricetin of embodiment 2 gently stimulates chronic unpredictability the effect of the depression of (CUMS) induction
It is 6-8 week by week old, body weight is that 25 ± 2g C57 mouse are randomly divided into five groups, including：Physiological saline group, model (CUMS is that chronic unpredictability is gently stimulated to group, is a kind of method of new construction depression model, it, which is mainly, passes through Different modes stimulate mouse, thus simulate human depression morbidity process and morbidity after some related symptoms, it is described later Model is CUMS modelings model), model+dihydromyricetin 10mg/kg groups, model+dihydromyricetin 20mg/kg groups and model + Venlafaxine 10mg/kg groups.First, to model+dihydromyricetin 10mg/kg groups, model+dihydromyricetin 20mg/kg groups and This three groups of chronic unpredictabilities of carry out of model+Venlafaxine group gently stimulate modeling, and modeling process continues eight weeks, modeling success Intraperitoneal injection was carried out to mouse according to dosage at the 9th week afterwards, successive administration carries out syrup preference, outstanding tail after seven days Experiment, forced swimming test, as a result respectively as shown in Fig. 2A, B, C.
As a result show：Dihydromyricetin gently stimulates chronic unpredictability the depression of induction to have certain treatment to make With.
The chronic unpredictability of embodiment 3 gently stimulates the change of GAP-associated protein GAP after modeling administration
Ethological mouse broken end will have been surveyed in embodiment 2 and has taken brain, the hippocampus in brain has been taken out, then passes through Western GAP-associated protein GAP (such as p-CREB, t-ERK1/2, CREB, BDNF, GSK3 β, pS9-GSK3 β, p- in Blot technical Analysis hippocampus ERK1/2 etc.) change, as a result as shown in Figure 3.
As a result show：Therapeutic action of the dihydromyricetin to depression is by strengthening ERK1/2, GSK3 β and CREB phosphorus Intracerebral BDNF contents are acidified and raise to realize.
All documents referred in the present invention are all incorporated as reference in this application, independent just as each document It is incorporated as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read, those skilled in the art can To be made various changes or modifications to the present invention, these equivalent form of values equally fall within the model that the application appended claims are limited Enclose.

Claims (10)

1. a kind of compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester purposes, it is characterised in that be used for The medicine of prevention or treatment depression is prepared,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 alcoxyls Base, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring with adjacent four carbon atom formation, and the hexatomic ring is by C1-C6 Alkyl replaces.
2. purposes as claimed in claim 1, it is characterised in that the compound of formula I, or derivatives thereof or its pharmaceutically may be used The salt or ester of receiving are selected from the group：
3. purposes as claimed in claim 1, it is characterised in that the depression is the depression being selected from the group：Minor depressive Disease, moderate depressive patients, major depressive disorder.
4. purposes as claimed in claim 1, it is characterised in that the medicine is included：
Component i)：Compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester；With
Component ii)：Pharmaceutically acceptable carrier.
5. purposes as claimed in claim 4, it is characterised in that component i) mass content is 0.01- in the medicine 99.99wt%.
6. purposes as claimed in claim 1, it is characterised in that the medicine is to the prevention or treatment of depression by improving brain Interior BDNF BDNF expression is realized.
7. a kind of medicine for being used to preventing or treating depression, it is characterised in that the medicine is included：
Component i)：Compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester, be used as active constituents of medicine；With
Component ii)：Pharmaceutically acceptable carrier；
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 alcoxyls Base, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring with adjacent four carbon atom formation, and the hexatomic ring is by C1-C6 Alkyl replaces.
8. medicine as claimed in claim 7, it is characterised in that the formulation of the medicine is selected from the group：Tablet, capsule, Granula, injection.
9. a kind of health products or beverage for being used to preventing or treating depression, it is characterised in that the health products or the beverage Comprising compound of formula I, or derivatives thereof or its pharmaceutically acceptable salt or ester,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 alcoxyls Base, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring with adjacent four carbon atom formation, and the hexatomic ring is by C1-C6 Alkyl replaces.
10. a kind of method for the expression for improving intracerebral BDNF BDNF, it is characterised in that by compound of formula I, Or derivatives thereof or its pharmaceutically acceptable salt or ester be applied to subject,
Wherein, R1、R2、R4、R5And R6It may be the same or different, be separately selected from the group：Hydroxyl, acetoxyl group, C1-C6 alcoxyls Base, C1-C6 cycloalkyloxies；
R3It is selected from the group：Hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
R7It is selected from the group：Hydrogen, hydroxyl, acetoxyl group, C1-C6 alkoxies, C1-C6 cycloalkyloxies；
Or R3And R7Contain 1 hetero atom O hexatomic ring with adjacent four carbon atom formation, and the hexatomic ring is by C1-C6 Alkyl replaces.
CN201710370269.2A 2017-05-23 2017-05-23 Purposes of the dihydromyricetin in terms of the medicine for the treatment of depression is prepared Pending CN107137391A (en)

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WO2023043076A1 (en) * 2021-09-17 2023-03-23 주식회사 인트론바이오테크놀로지 Alternative novel material to botulinum neurotoxin and preparation method therefor

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WO2023043076A1 (en) * 2021-09-17 2023-03-23 주식회사 인트론바이오테크놀로지 Alternative novel material to botulinum neurotoxin and preparation method therefor
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KR102627564B1 (en) 2021-09-17 2024-01-23 주식회사 인트론바이오테크놀로지 Alternative novel material to botulinum neurotoxin and preparing method thereof

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