CN105920143A - Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression - Google Patents
Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression Download PDFInfo
- Publication number
- CN105920143A CN105920143A CN201610268375.5A CN201610268375A CN105920143A CN 105920143 A CN105920143 A CN 105920143A CN 201610268375 A CN201610268375 A CN 201610268375A CN 105920143 A CN105920143 A CN 105920143A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- extract
- fructus gardeniae
- depression
- crude drug
- 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
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)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a pharmaceutical composition, which consists of such raw materials as herba hyperici perforati and fructus gardeniae. The invention also provides a pharmaceutical preparation containing the pharmaceutical composition. In addition, the invention also provides applications of the pharmaceutical composition and the pharmaceutical preparation in preparing medicines for treating depression. Pharmacodynamic tests prove that the pharmaceutical composition disclosed by the invention has an obvious curative effect on the depression; therefore, a new choice is provided for the clinical treatment of the depression.
Description
Technical field
The invention belongs to medical science and pharmaceutical field, be specifically related to a kind of new medicine group for treating depression
Compound and medical usage thereof.
Background technology
Depression, also known as depressive disorder, with significantly and persistently (more than at least 2 weeks, the even up to several years)
Mental state low for main clinical characteristics, be the main Types of mood disorders.Clinical visible mental state low with
Its situation is unbecoming, and the downhearted of emotion can be from depressed to extremely grieved, depression of feeling oneself inferior, even sad
See world-weary, can have suicidal attempt or behavior；Even occur numb；Some cases has obvious anxiety and fortune
Dynamic property is intense；Severe patient may occur in which the psychotic symptoms such as hallucination, vain hope.
Depression is a kind of high prevalence, high Disease Spectrum, high relapse rate, high disability rate, high homicide rate
Chronic mental illness.Adding up according to World Health Organization (WHO), whole world depression rate is about 11%, the whole world
There are about 3.4 hundred million patients with depression.Serious patient have 15% suicide can be selected to carry out end lives, 2/3
Patient once had the thought committed suiside, and was up to 1,000,000 because of the Population size estimation of depression committed suicide every year.When
Front depression has become as the fourth-largest disease in the world, it is contemplated that may will become to the year two thousand twenty and be only second to heart disease
The second largest illness of the mankind.The investigation of China's depression disease condition on a large scale is not the most carried out, and simply exists
The prevalence survey of depression has been carried out in different areas.Existing data show China's depression prevalence
The comparison in difference of each department is big, between 1.6%-4.1%.In view of the low consultation rate of China's patients with depression,
The rate of actually occurring should be higher.
Along with genomics, brain iconography, the going deep into of Neuroscience Research, " naturally " magazine in 2010
It is brain development disease that chief editor Philip Campbel proposes depression, and so far, depression belongs to function
The idea of property disease is thoroughly corrected, and therefore, Drug therapy remains the primary hand of current treating depression
Section.Since the eighties in 20th century, the research for the treatment of depression achieves significant progress, particularly
The birth of the 3rd generation antidepressants serotonin reuptake inhibitor, opens the new page for the treatment of depression,
Within 10 years subsequently, in succession develop the 4th generation 5-hydroxy tryptamine and Norepinephrine dual pathways reuptake inhibitor
(SNRI class, such as venlafaxine), 5-hydroxy tryptamine and Norepinephrine dual pathways regulator (NaSSa class,
Such as mirtazapine), work out personalized therapy program for doctor to patient and provide safer, more effective, more
Medicament selection.Although the 3rd, 4 generation antidepressants have higher treatment remission rate, more preferable toleration and
Become a line antidepressant drug, and centering, major depressive disorder also have a good curative effect, but current one
The cure rate of line antidepressant drug is only 30%, and onset time 2-4 (Wang Zuxin. the medicine of depression is controlled
Treat [J]. CHINESE JOURNAL OF INTERNAL MEDICINE, 1998,37 (11): 783).In recent years, the chlorine of the up-to-date focus of drug research
Amine ketone has the feature of quick acting.Research shows ketamine to treat depression 4～72h treated effect
And cure rate average out to 77% and 43%, but maintain curative effect time shorter (Murrough J W, et al.R
apid and longer-term antidepressant effects of repeated ketamine infusions in
Treatment-resistant major depression [J] .Biol Psychiatry, 2013,74 (4): 250
-256).
Except classical chemicals Research idea, pharmaceuticals researcher and mechanism are also actively working to from include
Medical herbs finds more efficient and safe anti-depression drug in number of ways such as interior natural drugs.
Herba Hyperici Monogyni (Hypericum perforatum L.) is also known as Herba Hyperici perforati, Hypericum perforatum L., for spun gold
Fructus Persicae section (being also called Guttiferae) hypericum, with all herbal medicine；Originate in Eurasia, quilt
It is referred to as Herba Hyperici perforati, is born in hillside, thick grass, ridge, roadside；China be then distributed in Hebei, Henan,
Shaanxi, Jiangsu, Jiangxi, Shandong, Sichuan, Guizhou etc. save.Herba Hyperici Monogyni acrid in the mouth, cold in nature, return liver
Warp, function dispersing the stagnated live-QI to relieve the stagnation of QI, clearing away heat-damp and promoting diuresis, detumescence lactogenesis, cure mainly that depression of liver-QI, feelings will is smooth, ambition
Gloomy, arthralgia, acute mastitis, breast are few.
Modern pharmacology research shows, extract of hypericum perforatum and active component hypericin can be treated
Depressed.Prior art occurs in that and has included controlling for depression of Herba Hyperici Monogyni (Herba Hyperici perforati)
The pharmaceutical composition treated.Such as publication number CN102961452A (publication date on March 13rd, 2013), send out
The Chinese invention patent of bright entitled " a kind of pharmaceutical composition for alleviating depression and preparation method thereof "
Application, discloses a kind of by 5-HTP (5-hydroxyryptophan) 20 parts, hydrochloric acid vitamin B615 parts, pass through leaf
Fructus Forsythiae extract 30 parts and the pharmaceutical composition of slips extract 30 parts composition.And for example publication number
CN102847050A (publication date on January 2nd, 2013), invention entitled " one is used for treating depression
The Chinese medicinal effective-part composition of disease " Chinese invention patent application, disclose one and include with Herba Hyperici perforati
Total flavones be the Herba Hyperici perforati extract of effective site, Rhizoma Curcumae Longae extract with curcumin as effective site,
The Chinese medicinal effective-part composition of the Radix Ginseng extract with ginsenoside as effective site.
Fructus Gardeniae (Gardenia jasminoides Ellis), calls Yellow Fructus Gardeniae, Fructus Gardeniae, white toad, is Rubiaceae
The fruit of plant Fructus Gardeniae.Fructus Gardeniae have hepatoprotective, function of gallbladder promoting, blood pressure lowering, calmness, stop blooding, the effect such as detumescence,
It is usually used in treating the diseases such as icterohepatitis, bruise, hypertension, diabetes at tcm clinical practice.Publication number
" one is used for nursing one's health in the Chinese invention application of CN105435178A (publication date on March 30th, 2016)
The Health-protection traditional Chinese medicinal preparation of depression ", the crude drug of disclosed Health-protection traditional Chinese medicinal preparation consist of Radix et Rhizoma Rhei (processed), Fructus Citri Sarcodactylis,
Radix Angelicae Sinensis, the Radix Paeoniae Alba, Poria, the Rhizoma Atractylodis Macrocephalae, Fructus Gardeniae, Rhizoma Zingiberis, Herba Menthae, Radix Glycyrrhizae.For another example publication number CN105056165A
(publication date on July 11st, 2015), entitled " a kind of medicine treating depression and preparation method thereof "
Chinese invention patent application, disclose a kind of by Rhizoma Cyperi (processed) 10～30 parts, Rhizoma Zingiberis 10～30 parts, Cape jasmine
Son 10～30 parts, Cortex Moutan 15～40 parts, Rhizoma Chuanxiong 15～40 parts, the Rhizoma Anemarrhenae 15～40 parts, Semen Ziziphi Spinosae
15～40 parts, Semen Platycladi 15～40 parts and Radix Glycyrrhizae Preparata 3～the medicines of 8 parts of compositions, be used for treating stagnation of liver-QI spleen
The mental disorder such as deficiency paralepsy, anxiety attack, panic attack, insomnia, obsession.
So far, yet there are no Herba Hyperici Monogyni and the report of Fructus Gardeniae combination treatment depression.
Summary of the invention
For the problems referred to above, it is an object of the present invention to provide and a kind of include Herba Hyperici Monogyni and Fructus Gardeniae
Pharmaceutical composition.The test of pesticide effectiveness shows, said composition has significant curative effect to depression, such that it is able to be clinical
Doctor and patient provide a kind of and treat the newly selected of depression.
In order to realize foregoing invention purpose, present invention employs following technical scheme:
A kind of pharmaceutical composition, crude drug is made up of Herba Hyperici Monogyni and Fructus Gardeniae.
Preferably, the crude drug of described pharmaceutical composition is by Herba Hyperici Monogyni 1～10 weight portion and Fructus Gardeniae 1～10
Weight portion forms.
A further object of the invention, is the medicine providing aforementioned pharmaceutical compositions in preparation treatment depression
In application.
As a preferred embodiment, the present invention provides a kind of pharmaceutical composition, and crude drug is by passing through leaf
Perforatum extract and Fructus Gardeniae extract composition.
Preferably, described extract of hypericum perforatum summary and discussion is no less than 0.30%, hyperforine
No less than 3.0%.
Preferably, described Fructus Gardeniae extract Determination of Gardenoside is not less than 50%.
Preferably, on the basis of the weight of described crude drug, described extract of hypericum perforatum accounts for
20%～60%, surplus is described Fructus Gardeniae extract.
It is furthermore preferred that on the basis of the weight of described crude drug, described extract of hypericum perforatum accounts for
30%～50%, surplus is described Fructus Gardeniae extract.
It is further preferred that on the basis of the weight of described crude drug, described extract of hypericum perforatum accounts for
40%～50%, surplus is described Fructus Gardeniae extract.
The present invention also provides for aforementioned pharmaceutical compositions application in the medicine of preparation treatment depression.
Adult to body weight 60 kilograms, (crude drug is for passing through Ye Jin for the aforementioned pharmaceutical compositions that the present invention provides
Silk Fructus Persicae extract and Fructus Gardeniae extract) quantity scope be oral 600～1200mg/ days.
A kind of pharmaceutical preparation containing aforementioned pharmaceutical compositions of offer is provided.
Described pharmaceutical preparation can be containing can also not containing pharmaceutically acceptable adjuvant.
Pharmaceutically acceptable adjuvant of the present invention, including (1) diluent (also known as filler),
Such as starch, sucrose, dextrin, calcium carbonate, calcium sulfate, light magnesium oxide, microcrystalline cellulose, mannitol, breast
Sugar, pregelatinized Starch；(2) disintegrating agent, such as dried starch, carboxymethyl starch sodium, low substituted hydroxy-propyl fiber
Element, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, gas-producing disintegrant etc.；(3) wetting agent, such as distillation
Water, ethanol etc.；(4) binding agent, such as Icing Sugar and syrup, starch slurry, polyvinylpyrrolidone, cellulose
Derivant, rubber cement, dextrin etc.；(5) lubricant, such as stearic acid, magnesium stearate, calcium stearate, micropowder
Silica gel, hydrogenated vegetable oil, Polyethylene Glycol；And the coloring agent of necessity, aromatic and sweeting agent etc..
The present invention also provides for the application in the medicine of preparation treatment depression of the said medicine preparation.
Application of the present invention, refers to that described pharmaceutical composition or described pharmaceutical preparation are independent, or and its
It has the chemical entities medicine of antidepressant activity or Chinese crude drug treats depression together.
The described chemical entities medicine with antidepressant activity includes but not limited to 1) tricyclic antidepressant, as
There are imipramine, amitriptyline, Clomipramine, doxepin, desipramine, nortriptyline, protriptyline etc.；
2) oxidase inhibitor (MAOI), such as irreversibility MAOIs (phenelzine, isocarboxazid and anti-benzene
Cyclopropylamine etc.) and selectivity MSOIs (moclobemide and brofaromine)；3) selectivity 5-hydroxy tryptamine (5-HT) is again
Uptake inhibitor (SSRIs), such as citalopram, fluoxetine, fluvoxamine, paroxetine and Sertraline)；4)
5-HT receptor antagonist；5) 5-HT cell reabsorption inhibitor, such as trazodone etc.；6) norepinephrine and many
Bar amine cell reabsorption inhibitor, such as amfebutamone and nefazodone etc.；7) 5-HT and norepinephrine heavily absorb
Inhibitor (SNRIs), such as venlafaxine etc..
The described Chinese crude drug with antidepressant effect includes but not limited to: Semen Ginkgo, Radix Bupleuri, Rhizoma Cyperi, Cortex Moutan,
Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, Radix Polygalae, Herba Menthae etc..
In the description of the present invention, without specified otherwise, " weight portion " refers to the weight between raw material
Proportion relation, according to practical situation, 1 weight portion can be 1g, 1kg, 10g etc..
Accompanying drawing explanation
Hereinafter, describe embodiment of the present invention in detail in conjunction with accompanying drawing, wherein:
Fig. 1 is illustrated that in test example 1 measurement result of DA content in each test group mice serum.In figure,
1 is blank group, and 2 is model group, and 3 is positive drug control group, and 4 is Fructus Gardeniae group, and 5 is Herba Hyperici Monogyni group,
6 is high dose group, and 7 is middle dosage group, and 8 is low dose group；" * * " expression compares P < 0.01 with blank group；
" ▲ ▲ " represent and compare P < 0.01 with model group.
Fig. 2 is illustrated that in test example 1 measurement result of NE content in each test group mice serum.In figure,
1 is blank group, and 2 is model group, and 3 is positive drug control group, and 4 is Fructus Gardeniae group, and 5 is Herba Hyperici Monogyni group,
6 is high dose group, and 7 is middle dosage group, and 8 is low dose group；" * * " expression compares P < 0.01 with blank group；
" ▲ ▲ " represent and compare P < 0.01 with model group.
Fig. 3 is illustrated that in test example 1 measurement result of 5-HT content in each test group Hippocampus of Mice.
In figure, 1 is blank group, and 2 is model group, and 3 is positive drug control group, and 4 is Fructus Gardeniae group, and 5 for passing through leaf spun gold
Fructus Persicae group, 6 is high dose group, and 7 is middle dosage group, and 8 is low dose group；" * * " represents and compares with blank group
P<0.01；" ▲ " represents compares P < 0.05 with model group, " ▲ ▲ " represent and compare P < 0.01 with model group.
Detailed description of the invention
The technical scheme that the present invention provides includes:
1. a pharmaceutical composition, crude drug is made up of Herba Hyperici Monogyni and Fructus Gardeniae.
2. a pharmaceutical composition, crude drug is by Herba Hyperici Monogyni 1～10 weight portion and Fructus Gardeniae 1～10 weight portion
Composition.
3. the preparation method of the pharmaceutical composition described in technical scheme 1 or 2, including by Herba Hyperici Monogyni and Cape jasmine
Son uses the solvent extraction that this area is conventional jointly or independently of one another, prepared by the method conventional according to this area
Become acceptable preparation clinically.
4. a pharmaceutical composition, crude drug is made up of extract of hypericum perforatum and Fructus Gardeniae extract.
5. a pharmaceutical composition, on the basis of the weight of described crude drug, described extract of hypericum perforatum
Accounting for 20%～60%, surplus is described Fructus Gardeniae extract.
6. a pharmaceutical composition, on the basis of the weight of described crude drug, described Herba Hyperici Monogyni extracts
Thing accounts for 30%～50%, and surplus is described Fructus Gardeniae extract.
7. a pharmaceutical composition, on the basis of the weight of described crude drug, described Herba Hyperici Monogyni extracts
Thing accounts for 40%～50%, and surplus is described Fructus Gardeniae extract.
8. a pharmaceutical preparation, including the pharmaceutical composition described in scheme 1,2,4,5,6 or 7, or
The pharmaceutical composition of scheme 3 preparation.
9. the pharmaceutical composition described in scheme 1,2,4,5,6 or 7 is in the medicine of preparation treatment depression
Application.
10. the pharmaceutical composition of scheme 3 preparation application in the medicine of preparation treatment depression.
11. the application that the pharmaceutical preparation described in scheme 8 is in the medicine of preparation treatment depression.
Application described in 12. schemes 9,10 or 11, individually uses including described pharmaceutical composition or pharmaceutical preparation
In treatment depression, or share with the chemical entities or Chinese crude drug with antidepressant activity.
Referring to specific embodiment, the present invention is described.It will be appreciated by those skilled in the art that these are real
Executing example and be merely to illustrate the present invention, it limits the scope of the present invention never in any form.
Experimental technique in following embodiment, if no special instructions, is conventional method.Following embodiment
In used medicinal raw material, reagent material etc., if no special instructions, be commercially available purchase product, wherein,
Extract of hypericum perforatum sheet, trade name Lu Youtai, the every dry extract Han Herba Hyperici Monogyni
300mg；Dr Willmar Schwabe produces, import drugs registration certificate number: Z20090005；
Extract of hypericum perforatum: containing hyperforine 3.0%, summary and discussion 0.30%；Purchased from Chongqing
Gao Ren bio tech ltd；
Fructus Gardeniae extract: containing jasminoidin 51.81%；Purchased from Gao Ren bio tech ltd, Chongqing.
Embodiment 1A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of:
Extract of hypericum perforatum 10.83g, Fructus Gardeniae extract 19.255g.
By said extracted thing mix homogeneously, to obtain final product.
Embodiment 2A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of:
Extract of hypericum perforatum 6.3g, Fructus Gardeniae extract 23.7g.
By said extracted thing mix homogeneously, to obtain final product.
Embodiment 3A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of:
Extract of hypericum perforatum 9.53g, Fructus Gardeniae extract 20.47g.
By said extracted thing mix homogeneously, to obtain final product.
Embodiment 4A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of:
Extract of hypericum perforatum 12.15g, Fructus Gardeniae extract 17.85g.
By said extracted thing mix homogeneously, to obtain final product.
Embodiment 5A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of: (1 weight portion=10g)
Herba Hyperici Monogyni 100g, Fructus Gardeniae 100g.
It is prepared via a method which:
Take Herba Hyperici Monogyni, with 50% ethanol extraction 2 times (1L/ time), each 1 hour, every time with 50%
Ethanol 1L, united extraction liquid, concentrate, be dried, obtain extract of hypericum perforatum.
Take Fructus Gardeniae, water extraction 3 times, each 1 hour, use water 1L every time；Merge aqueous extract, be concentrated into
In right amount, after ethanol precipitation process, supernatant recovery ethanol is extremely without alcohol taste, upper macroporous adsorptive resins absorption
Process, 50～70% ethanol solution eluting, reclaim ethanol, be spray-dried, obtain Fructus Gardeniae extract.
Above-mentioned extract of hypericum perforatum and Fructus Gardeniae extract are mixed, adds conventional adjuvant, according to ability
The method of territory routine is prepared as tablet.
Embodiment 6A kind of pharmaceutical composition
The raw material of described pharmaceutical composition consists of: (1 weight portion=500g)
Herba Hyperici Monogyni 1kg, Fructus Gardeniae 500g.
Herba Hyperici Monogyni and Fructus Gardeniae are mixed, extract 3 times with 50% ethanol solution (concentration of volume percent),
Each 1 hour, use 9L50% ethanol, united extraction liquid every time, concentrate, add this area customary adjuvant,
Pelletize, encapsulated, to obtain final product.
Test example 1The anti-reserpine of pharmaceutical composition of the present invention causes the pharmacodynamic study that mice is depressed
Laboratory animal and experimental drug
1. laboratory animal: SPF level ICR mice, male, 150, body weight 18-21g, this Lay of Hunan
Ke Jingda laboratory animal company limited provides, credit number: SCXK (Hunan) 2011-0003.
2. experimental drug
Extract of hypericum perforatum: containing hyperforine 3.0%, summary and discussion 0.30%；Purchased from Chongqing
Gao Ren bio tech ltd；
Fructus Gardeniae extract: containing jasminoidin 51.81%；Purchased from Gao Ren bio tech ltd, Chongqing.
Clomipramine Hydrochloride: purchased from Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, lot number: 22150401.
Reserpine: purchased from Chengdu Puffy moral Bioisystech Co., Ltd, lot number: 150314.
Animal feeding:
Indoor temperature (18 DEG C～24 DEG C), (10g/100g body weight d), drinking-water (changes weekly water 2～3 to food-intake
Secondary).
Laboratory animal packet and dosage regimen
1. animal packet and dosage: experiment mice is randomly divided into 5 groups, often 10 mices of group, 5/
Cage, often organizes 2 cages.
1. blank group: normal saline (NaCl 9g/L), gavage, 1ml/100g body weight sky
2. model group: with " blank group "
3. positive controls: Clomipramine Hydrochloride, 40mg kg-1·d-1
4. Fructus Gardeniae group: Fructus Gardeniae extract 144mg kg-1·d-1
5. Herba Hyperici Monogyni group:(Dr Willmar Schwabe produces, import drugs registration certificate
Number: Z20090005), 136.08mg kg-1·d-1
6. high dose group: the pharmaceutical composition (extract of hypericum perforatum+Fructus Gardeniae extract) of embodiment 1,
451.28mg·kg-1·d-1
Middle dosage group: the pharmaceutical composition of embodiment 1,225.64mg kg-1·d-1
8. low dose group: the pharmaceutical composition of embodiment 1,112.82mg kg-1·d-1
2. drug solution preparing:
1. the preparation of reserpine solution: dosage is 4mg kg-1, take 0.04g reserpine powder, with a small amount of
Physiological saline solution, is settled in 100ml volumetric flask, and configuration concentration is 0.4mg ml-1。
2. the preparation of normal saline: weigh 9g sodium chloride, is settled in 1000ml volumetric flask with distilled water.
3. the preparation of positive drug medicinal liquid: take Clomipramine Hydrochloride, remove coating, be crushed to powder, weigh 0.2667g
Powder, uses a small amount of physiological saline solution, is settled in 100ml volumetric flask, and configuration concentration is 2.667mg ml-1。
4. the preparation of Fructus Gardeniae extract medicinal liquid: by the amount of being given daily 144mg kg-1·d-1, weigh Fructus Gardeniae extract
0.9600g, uses a small amount of physiological saline solution, is settled in 100ml volumetric flask, and configuration concentration is 9.6mg ml-1。
5. the preparation of extract of hypericum perforatum medicinal liquid: takeSheet 0.9072g, uses a small amount of normal saline
Dissolve, be settled in 100ml volumetric flask.
6. the preparation of high dose group medicinal liquid: take extract of hypericum perforatum 1.0830g, Fructus Gardeniae extract 1.9255g,
Mixing, uses a small amount of physiological saline solution, is settled in 100ml volumetric flask.
The preparation of middle dosage group medicinal liquid: take extract of hypericum perforatum 0.5415g, Fructus Gardeniae extract 0.9627g,
Mixing, uses a small amount of physiological saline solution, is settled in 100ml volumetric flask.
8. the preparation of low dose group medicinal liquid: take extract of hypericum perforatum 0.2708g, Fructus Gardeniae extract 0.4813g,
Mixing, uses a small amount of physiological saline solution, is settled in 100ml volumetric flask.
4. dosage regimen
Each group gavage gives medicine or normal saline, every day 1 time, and successive administration 7d (is administered volume all to press
0.015mL·g-1·d-1)；After last is administered, in addition to blank group, other respectively organizes lumbar injection 4mg kg-1
Reserpine, intraperitoneal injection volume presses 0.01ml g-1·d-1。
Experimentation and result:
1. the observation of temperature decline:
Last is administered after 4h and thermometer probe is inserted mice anal, the degree of depth with thermometer probe completely into
Anus is as the criterion, and maintains at least 2min.Record each group of data, compare the difference of body temperature in administration group and matched group.
Concrete outcome is shown in Table 1.
Body temperature measurement result respectively organized by table 1
Note: comparing with blank group, * represents that P < 0.05, * * represents P < 0.01；Compare with model group,▲Represent P < 0.05.
Data analysis:
(1) after model group mouse peritoneal injection reserpine, body temperature compares reduction highly significant with blank group
(P < 0.01), shows that reserpine causes depression model modeling success.
(2) comparing with model group, positive controls, Herba Hyperici Monogyni group and low dose group all have significance difference
Different (P < 0.05), and effect is quite, there was no significant difference.But analyzing from average, low dose group raises and presses down
The body temperature effect of strongly fragrant mice is better than extract of hypericum perforatum group.
(3) although not having significant difference, but high dose group also can raise the body temperature of depressed mice.
(4) alone Fructus Gardeniae extract, has no significant effect the body temperature of depressed mice.
Above-mentioned test illustrates, the pharmaceutical composition of the present invention raises depressed mouse temperature reduction caused by reserpine to be had
Preferably effect, wherein the effect of low dose group is suitable with positive drug.In terms of raising depressed mouse temperature,
Pharmaceutical composition effect of the present invention is better than alone Fructus Gardeniae extract and extract of hypericum perforatum.
2. NE (norepinephrine) in mice serum, 5-HT (5-hydroxyl color in DA (dopamine) and cerebral tissue
Amine) mensuration of content
8h after last is administered, plucks eyeball and takes blood, and taken blood is stood 1 hour, centrifugal
(3000r/min, 20min), takes supernatant and is placed in EP pipe, and cryopreservation is to be measured.After taking blood, at broken end
Dead animal, peels off brain on ice pan, removes cerebellum and olfactory bulb, retain remaining whole brain tissue, use tinfoil paper
Paper bag is wrapped up in ,-70 DEG C of preservations.Add 9 times of PBS (pH7.4) homogenate, make 10% brain tissue homogenate's liquid, by even
Serosity is inserted in centrifuge tube, with 3000r/min centrifugation 20min under the conditions of 4 DEG C, carefully receives after standing
Collection supernatant, is placed in 2mlEP pipe, and-70 DEG C of preservations are to be measured.
Use NE, DA in ELISA method detection mice serum, and the content of cerebral tissue 5-HT.Result is shown in
Table 2 and Fig. 1～Fig. 3.
The assay result of neurotransmitter in table 2 mice serum and cerebral tissue
Note: comparing with blank group, * represents that P < 0.05, * * represents P < 0.01；Compare with model group,▲Represent P < 0.05,▲▲Represent P < 0.01
Data analysis:
1) medicine is on the impact of DA content in depressed mice serum:
(1) in model group mice serum, DA content significantly reduces, and compares with blank group that to have pole significance poor
Different (P < 0.01), shows that reserpine causes depression model modeling success.
(2) compare with model group, each dose of the pharmaceutical composition of positive drug group, Herba Hyperici Monogyni group and the present invention
In amount group mice serum, DA content all pole dramatically increases (P < 0.01)；The DA level of above-mentioned each group is with blank
Group compares and is not significantly different from.High, normal, basic dose of the pharmaceutical composition of extract of hypericum perforatum and the present invention is described
Amount all can significantly raise DA content in depressed mice serum, acts on suitable with positive drug.But from DA water
Flat horizontal values is seen, in the depressed mice serum of extract of hypericum perforatum group rising, the effect of DA is not as good as this
Bright pharmaceutical composition.
(3) although Fructus Gardeniae extract also can significantly improve DA concentration, but DA concentration compares with blank group
Still there were significant differences (P ＜ 0.05).Illustrate that in Fructus Gardeniae extract increasing serum, the action intensity of DA level is too late
The pharmaceutical composition of the present invention.
2) medicine is on the impact of NE content in depressed mice serum:
(1) in model group mice serum, NE content significantly reduces, and compares with blank group that to have pole significance poor
Different (P < 0.01), shows that reserpine causes depression model modeling success.
(2) comparing with model group, in all administration group mice serums, NE content all pole dramatically increases (P < 0.01),
Pharmaceutical composition (high, medium and low dosage), Fructus Gardeniae extract and the extract of hypericum perforatum of the present invention are described
All tools can significantly improve the content of NE in serum.
(3) compare with blank group, pharmaceutical composition low dose group of the present invention and the NE level of Fructus Gardeniae group
There is no significant difference (P ＞ 0.05)；Illustrate that this low dosage and Fructus Gardeniae extract raise the effect of NE content
By force.
3) medicine is on the impact of 5-HT content in depressed Mice brain tissues
(1) in model group Mice brain tissues, 5-HT content significantly reduces, compare with blank group have the most notable
Sex differernce (P < 0.01), shows that reserpine causes depression model modeling success.
(2) compare with model group, positive drug group and pharmaceutical composition senior middle school of the present invention low dose group mice
In cerebral tissue, 5-HT content all pole dramatically increases (P < 0.01)；Three agent of pharmaceutical composition of the present invention are described
Amount all can significantly raise 5-HT content in depressed Mice brain tissues, acts on suitable with positive drug.
(3) Fructus Gardeniae extract and extract of hypericum perforatum also are able to significantly improve 5-HT content (P < 0.05),
But effect is weaker than pharmaceutical composition of the present invention each dosage group.
Experiment conclusion
Caused by reserpine, depressed mice all shows as exception in every physical signs, as body temperature significantly reduce, blood
Related neurotransmitters level in cleer and peaceful cerebral tissue significantly reduces.Herba Hyperici Monogyni of the present invention and Fructus Gardeniae
Constitute pharmaceutical composition, it is possible to reverse above-mentioned abnormal physical signs, demonstrate depression is had good
Drug effect, and effect is the most suitable with positive drug；Particularly, the pharmaceutical composition low dose group of the present invention raises
In depressed mice serum, the effect of NE level is better than positive control drug.Therefore, summary effect experiment result,
The effect of the medicine composite for curing depression of the present invention is better than Clomipramine Hydrochloride.
Fructus Gardeniae extract is alone, not affects the body temperature of depressed mice；It addition, it raises depressed Mouse Blood
In clear middle DA level and brain, the effect of 5-HT level is also not as good as the pharmaceutical composition low dose group of the present invention.Pass through
Leaf perforatum extract is alone, raises in depressed mouse temperature, mice serum 5-HT in DA and NE and brain
The effect of level is also not as good as the low dose group of pharmaceutical composition of the present invention.Above-mentioned test shows, Fructus Gardeniae and passing through
Leaf Radix Hyperici Monogyni (Herba Hyperici Monogyni) use in conjunction, is significantly stronger than alone Fructus Gardeniae or Herba Hyperici Monogyni for depressed therapeutical effect.
In a word, the invention provides a kind of new pharmaceutical composition that may be used for treatment depression, raw material is by passing through
Leaf Radix Hyperici Monogyni (Herba Hyperici Monogyni) and Fructus Gardeniae composition.Pharmacodynamics test shows, the pharmaceutical composition of the present invention is to depression model animal
There is the pharmaceutical composition of significant curative effect, especially low dosage, at regulation related biochemical indicator and neurotransmitter
Aspect, effect is better than the Clomipramine Hydrochloride of prior art.
Specific description of embodiments of the present invention above is not limiting as the present invention, and those skilled in the art are permissible
Make various change or deformation according to the present invention, without departing from the spirit of the present invention, the present invention all should be belonged to
Scope of the following claims.
Claims (10)
1. a pharmaceutical composition, crude drug is made up of Herba Hyperici Monogyni and Fructus Gardeniae.
Pharmaceutical composition the most according to claim 1, it is characterised in that described pharmaceutical composition
Crude drug be made up of Herba Hyperici Monogyni 1～10 weight portion and Fructus Gardeniae 1～10 weight portion.
3. a pharmaceutical composition, crude drug is made up of extract of hypericum perforatum and Fructus Gardeniae extract.
Pharmaceutical composition the most according to claim 3, it is characterised in that described Herba Hyperici Monogyni
Extract summary and discussion is no less than 0.30%, and hyperforine is no less than 3.0%；
Preferably, described Fructus Gardeniae extract Determination of Gardenoside is no less than 50%.
5. according to the pharmaceutical composition described in claim 3 or 4, it is characterised in that with described raw material
On the basis of the weight of medicine, described extract of hypericum perforatum accounts for 20%～60%, and surplus is described Fructus Gardeniae
Extract.
Pharmaceutical composition the most according to claim 5, it is characterised in that with described crude drug
On the basis of weight, described extract of hypericum perforatum accounts for 30%～50%, and surplus is that described Fructus Gardeniae is extracted
Thing.
Pharmaceutical composition the most according to claim 6, it is characterised in that with described crude drug
On the basis of weight, described extract of hypericum perforatum accounts for 40%～50%, and surplus is that described Fructus Gardeniae is extracted
Thing.
8. the pharmaceutical preparation containing the pharmaceutical composition according to any one of claim 1 to 7；
Preferably, described pharmaceutical preparation can be containing can also not containing pharmaceutically acceptable adjuvant.
9. pharmaceutical composition according to any one of claim 1 to 7, or the medicine described in claim 8
Preparation application in the medicine of preparation treatment depression.
Application the most according to claim 9, it is characterised in that described pharmaceutical composition or described
Pharmaceutical preparation is independent, or the chemical entities medicine that has antidepressant activity with other or Chinese crude drug one
Play treatment depression；
The described chemical entities medicine with antidepressant activity selected from imipramine, amitriptyline, Clomipramine,
Doxepin, desipramine, nortriptyline, protriptyline, phenelzine, isocarboxazid, tranylcypromine,
Moclobemide, brofaromine, citalopram, fluoxetine, fluvoxamine, paroxetine, Sertraline,
One or more in trazodone, amfebutamone, nefazodone, venlafaxine；
The described Chinese crude drug with antidepressant effect selected from Semen Ginkgo, Radix Bupleuri, Rhizoma Cyperi, Cortex Moutan, Semen Ziziphi Spinosae,
One or more in the Rhizoma Anemarrhenae, Radix Polygalae, Herba Menthae.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610268375.5A CN105920143A (en) | 2016-04-27 | 2016-04-27 | Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610268375.5A CN105920143A (en) | 2016-04-27 | 2016-04-27 | Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105920143A true CN105920143A (en) | 2016-09-07 |
Family
ID=56837296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610268375.5A Pending CN105920143A (en) | 2016-04-27 | 2016-04-27 | Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105920143A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110538232A (en) * | 2019-09-30 | 2019-12-06 | 青岛琛蓝医药科技发展有限公司 | Anti-depression compound preparation and preparation method thereof |
| CN110780004A (en) * | 2019-11-14 | 2020-02-11 | 美国琛蓝营养制品股份有限公司 | Method for establishing fingerprint of traditional Chinese medicine composition or preparation thereof with depression mood regulating effect |
| CN110772564A (en) * | 2019-11-14 | 2020-02-11 | 美国琛蓝营养制品股份有限公司 | Traditional Chinese medicine extract composition with depression mood regulating effect, preparation method thereof and traditional Chinese medicine preparation |
| CN112741886A (en) * | 2019-10-30 | 2021-05-04 | 唐启盛 | Traditional Chinese medicine composition for treating anxiety and depression |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101390971A (en) * | 2007-09-20 | 2009-03-25 | 中国医学科学院药物研究所 | Use of capejasmine effective part in treating anti-depression anxiety |
-
2016
- 2016-04-27 CN CN201610268375.5A patent/CN105920143A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101390971A (en) * | 2007-09-20 | 2009-03-25 | 中国医学科学院药物研究所 | Use of capejasmine effective part in treating anti-depression anxiety |
Non-Patent Citations (3)
| Title |
|---|
| 张筱: "贯叶金丝桃素的分离纯化研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
| 石景洋等: "栀子豉汤治疗抑郁证患者44 例疗效观察", 《中国实验方剂学杂志》 * |
| 马丽娜: "抗抑郁药物研究进展", 《医学综述》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110538232A (en) * | 2019-09-30 | 2019-12-06 | 青岛琛蓝医药科技发展有限公司 | Anti-depression compound preparation and preparation method thereof |
| CN112741886A (en) * | 2019-10-30 | 2021-05-04 | 唐启盛 | Traditional Chinese medicine composition for treating anxiety and depression |
| CN112741886B (en) * | 2019-10-30 | 2022-02-18 | 唐启盛 | Traditional Chinese medicine composition for treating anxiety and depression |
| CN110780004A (en) * | 2019-11-14 | 2020-02-11 | 美国琛蓝营养制品股份有限公司 | Method for establishing fingerprint of traditional Chinese medicine composition or preparation thereof with depression mood regulating effect |
| CN110772564A (en) * | 2019-11-14 | 2020-02-11 | 美国琛蓝营养制品股份有限公司 | Traditional Chinese medicine extract composition with depression mood regulating effect, preparation method thereof and traditional Chinese medicine preparation |
| WO2021093091A1 (en) * | 2019-11-14 | 2021-05-20 | 美国琛蓝营养制品股份有限公司 | Method for establishing fingerprint spectrum of traditional chinese medicine composition having effect of regulating low mood or preparation thereof |
| WO2021093090A1 (en) * | 2019-11-14 | 2021-05-20 | 美国琛蓝营养制品股份有限公司 | Traditional chinese medicine extract composition having function of regulating depression, preparation method therefor, and chinese medicine preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1994451B (en) | Chinese medicinal composition for treating depression, its preparation method and application | |
| CN101244244B (en) | Depression treating medicine composition and preparation method thereof | |
| CN100404035C (en) | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease | |
| CN100522212C (en) | Traditional Chinese medicine composition for treating depression and its preparing method | |
| CN105920143A (en) | Pharmaceutical composition comprising herba hyperici perforati and fructus gardeniae and medical application of pharmaceutical composition in resisting depression | |
| CN101711847B (en) | Oral traditional Chinese medicine preparation for treating melancholia and anxiety neurosis | |
| CN102258742B (en) | Chinese medicinal medicine composition for treating depression and preparation method thereof | |
| CN103566087B (en) | Pharmaceutical composition for treating cognitive disorder and application thereof in preparation of medicine for treating Alzheimer disease | |
| CN101069734A (en) | Chinese medicine composition for vascular cretinism and preparing method therefor | |
| CN105853479A (en) | Pharmaceutical composition for treating depression | |
| CN102283910B (en) | Chinese medicinal composition with anti-depression effect and preparation and preparation method thereof | |
| CN101843682A (en) | Maxingshigan injecta and preparation method thereof | |
| CN101607031B (en) | Medicated wine for curing and preventing diabetes mellitus, preparation method and application method thereof | |
| CN101919924B (en) | Pharmaceutical composition for curing tristimania and preparation method and application thereof | |
| CN104306662A (en) | Traditional Chinese medicine composition for treating neurasthenia and preparation method thereof | |
| CN111053854B (en) | Traditional Chinese medicine preparation with depression treatment effect and preparation method and application thereof | |
| CN100444849C (en) | New use of tribulus terrestris extraction | |
| CN1919252B (en) | Medicine for treating cardiovascular and cerebrovascular disease | |
| CN1579485B (en) | Traditional Chinese medicinal composition for treating intestinal function disorder and its preparation method | |
| CN106852973A (en) | A kind of traditional Chinese medicine extract composition, Its Preparation Method And Use | |
| CN104435298A (en) | Anti-depression pharmaceutical composition | |
| CN1283312C (en) | Antidepressant composition and preparing process thereof | |
| CN1919253B (en) | Cardiac and cerebral vascular disease treating medicinal composition | |
| CN104606636B (en) | A kind of Chinese medicine composition for treating depression and preparation method thereof | |
| CN100375626C (en) | Chinese medicine compound preparation for treating depression and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160907 |
|
| RJ01 | Rejection of invention patent application after publication |