CN105770396A

CN105770396A - Anti-depression medical application of yiguan decoction

Info

Publication number: CN105770396A
Application number: CN201610202456.5A
Authority: CN
Inventors: 张海燕; 杨明; 杨启悦; 赖琼; 宋民宪; 刘洋
Original assignee: Jiangxi University of Traditional Chinese Medicine
Current assignee: Jiangxi University of Traditional Chinese Medicine
Priority date: 2016-04-05
Filing date: 2016-04-05
Publication date: 2016-07-20

Abstract

The invention provides an anti-depression medical application of a yiguan decoction. The yiguan decoction is prepared from the following traditional Chinese medicinal materials in parts by weight: 10 parts of radix glehniae, 10 parts of radix ophiopogonis, 10 parts of angelica sinensis, 30 parts of dried rehamnnia roots, 12 parts of wolfberry fruits and 5 parts of szechwan chinaberry fruits.

Description

The antidepressant medical usage of YIGUANJIAN

Technical field

The invention belongs to medical domain, be specifically related to the medical usage that YIGUANJIAN is new.

Background technology

YIGUANJIAN, is created by Qing Dynasty well-known doctor Mr. Wei Zhi, sees " Xu Mingyi Lei heart stomachache door ".Wei Shi says: " rule hypochondriac pain, acid regurgitation, hernia abdominal mass, all hepatopathys." it is the famous prescription of nourishing YIN and dispersing the stagnated liver-QI.The party is made up of Radix Glehniae, Radix Ophiopogonis, dry ground, Radix Angelicae Sinensis, Fructus Lycii and Fructus Toosendan 6 taste.Research shows; YIGUANJIAN has multiple pharmacotoxicological effect: 1) protection gastric mucosa, anti-ulcer effect (Li Lin, Wang Zhuli, etc. the effect [J] of the anti-dehydrated alcohol gastric mucosa injury of YIGUANJIAN. Chinese digests magazine; 1998,6 (6): 519-520；Li Lin, Liu fragrant plant, etc. the anti-acute experiment gastric ulcer of YIGUANJIAN and promotion ulcer healing effect [J]. Guangdong medical science, 1998,19 (5): 328-330).2) to the preventive and therapeutic effect of experimental hepatosis (Chen Yongxiang, Jin Fengyun, etc. YIGUANJIAN on the impact of SOD in Mice and LPO with protect the liver Exploration of Mechanism [J]. Guiyang College of Traditional Chinese Medicine's journal, 1996,18 (3): 62-63；Chen Yongxiang, Wang Hesheng, etc. the impact [J] of YIGUANJIAN and Polysaccharides on Mice hepatic injury and SOD, LPO. Chinese Pharmaceutical Journal, 1999,34 (4): 239-241).3) supplement and regulating microelement (Yu Wenjun. the discussion [J] of YIGUANJIAN medium trace element and decoct PH and therapeutical effect relation. Guiyang College of Traditional Chinese Medicine's journal, 1990, (3): 63-64).4) anti-aging effects (Wang Hesheng, Chen Yongxiang, etc. in YIGUANJIAN Polysaccharides on Mice erythrocyte and tissue in SOD activity effect [J]. Guiyang Medical College journal, 1996,21 (4): 297-298；Jin Fengyun, Chen Yongxiang, etc. the impact [J] of Polysaccharides on Mice SOD activity and LPO content in YIGUANJIAN. Pharmacology and Clinics of Chinese Materia Medica, 1997,13 (5): 15-16).5) antifatigue effect (Chen Yongxiang, Zhang Hongli, etc. " YIGUANJIAN " experimentation [J]. Pharmacology and Clinics of Chinese Materia Medica, 1989, (1): 21-21).6) impact on immunologic function, YIGUANJIAN can effectively antagonism corticosterone on the suppression of cellular immunization (Cai Dingfen. the YIGUANJIAN impact [J] on corticosterone Mus cellular immunization and cytokine. China Immunology Journal, 1999,15 (11): 45-45).7) antibacterial and anti-inflammation functions (Chen Yongxiang, Zhang Hongli, etc. YIGUANJIAN experimentation [J]. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1989,14 (9): 42-42).

But in clinical practice, the prescription of " YIGUANJIAN " by name is used for treating multiple disease, such as diabetes, hepatitis, hepatic fibrosis, hepatocarcinoma, gastritis, gastroduodenal ulcer, cardiovascular diseases, oculopathy and dermatosis etc..But these prescriptions all differ greatly with ancient prescription original intention at dosage, prescription.As, Mei Haiyun is reported on the basis of Western medicine blood sugar lowering and plus-minus YIGUANJIAN treatment type 2 diabetes mellitus companion anxiety-depression determined curative effect is administered orally, (on Western medicine blood sugar lowering basis oral oryzanol) is compared with matched group, fasting glucose (FBG) before and after patient treatment, 2h-plasma glucose (2h-PG) and glycolated hemoglobin (HbAlc) level decline more, and Analysisof Self-rating Anxiety Scale (SAS) and self rating depressive scale (SDS) scoring are decreased obviously (P < 0.05) (Mei Haiyun, plus-minus YIGUANJIAN treatment type 2 diabetes mellitus companion's anxiety-depression 30 example clinical research [J]. Jiangsu Chinese medicine .2014, 46 (6): 33-34).But consisting of of the plus-minus YIGUANJIAN used by this clinical research: Radix Rehmanniae 20g, Radix Glehniae 10g, Radix Ophiopogonis 10g, Radix Angelicae Sinensis 10g, Fructus Lycii 10g, Radix Paeoniae Alba 15g, Fructus Toosendan 6g, Radix Bupleuri 10g, Rhizoma Cyperi 10g, Radix Curcumae 10g, Semen Ziziphi Spinosae 15g, Flos Albiziae 15g；Forming by the non-YIGUANJIAN ancient prescription of the flavour of a drug of half in side, and the merit of the Radix Paeoniae Alba increased, Radix Bupleuri, Rhizoma Cyperi, Radix Curcumae, Semen Ziziphi Spinosae and Herba Albiziae Huadu mainly row dispersing the stagnated live-QI to relieve the stagnation of QI.For another example, female adult rat is adopted the chronic imprevision that castration+orphan supports+improves method stress set up involutional depression model by the report such as Liu Yanling；YIGUANJIAN adds taste gavage, and rat hippocampus, cortex 5-HTR1AmRNA transcriptional level are significantly higher than model group, Western medicine group (fluoxetine), has significant difference (P < 0.01).Therefore researcher thinks that YIGUANJIAN adds taste and affects 5-HTR1AmRNA functional transcription from gene level, thus playing its antidepressant effect (Liu Yanling, Song Zhuomin. YIGUANJIAN adds the taste treatment [J] to rat chronic imprevision Stress model involutional depression. new Chinese medicine and clinical pharmacology .2010,21 (4): 346-350)." YIGUANJIAN adds taste " extractum used in this research, medicine is made up of Radix Rehmanniae Preparata 30g, Rhizoma Pinelliae 15g, Radix Glehniae 20g, Radix Ophiopogonis 20g, Caulis Perillae 10g, Cortex Magnoliae Officinalis 10g, Pericarpium Citri Reticulatae 10g, Poria cum Radix Pini 15g, Rhizoma Acori Graminei 6g, Radix Curcumae 10g, Fructus Amomi 6g.In side, the Rhizoma Pinelliae, Caulis Perillae, Cortex Magnoliae Officinalis, Pericarpium Citri Reticulatae, Poria cum Radix Pini, Rhizoma Acori Graminei, Radix Curcumae, Fructus Amomi are all that ancient prescription does not occur, the Fructus Toosendan in ancient prescription is then omitted.

Visible, the prescription plus-minus run after fame with " YIGUANJIAN " in prior art is too many, it is difficult to determine that whether the curative effect of report is the curative effect of ancient prescription itself.

Summary of the invention

For the problems referred to above, it is an object of the present invention to provide the medical usage that YIGUANJIAN treatment depression is new.

In order to realize foregoing invention purpose, present invention employs following technical scheme:

YIGUANJIAN purposes in the medicine of preparation treatment depression；Wherein said YIGUANJIAN is made up of the Chinese crude drug of following weight portion:

Radix Glehniae 10 weight portion, Radix Ophiopogonis 10 weight portion, Radix Angelicae Sinensis 10 weight portion, Radix Rehmanniae 30 weight portion, Fructus Lycii 12 weight portion, Fructus Toosendan 5 weight portion.

Described medicine can also include the chemical entities with antidepressant activity.

The described chemical entities with antidepressant activity includes but not limited to 1) tricyclic antidepressant, if any imipramine, amitriptyline, Clomipramine, doxepin, desipramine, nortriptyline, protriptyline etc.；2) oxidase inhibitor (MAOI), such as irreversibility MAOIs (phenelzine, isocarboxazid and tranylcypromine etc.) and selectivity MSOIs (moclobemide and brofaromine)；3) selectivity 5-hydroxy tryptamine (5-HT) reuptake 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 dopamine cell reabsorption inhibitor, such as amfebutamone and nefazodone etc.；7) 5-HT and norepinephrine cell reabsorption inhibitor (SNRIs), such as venlafaxine etc..

Described medicine can contain can not also contain pharmaceutically acceptable adjuvant.

Described medicine is oral formulations, includes but not limited to decoct, powder, tablet, capsule, soft capsule, effervescent tablet, oral instant membrane, oral cavity disintegration tablet, oral liquid.

Pharmaceutically acceptable adjuvant of the present invention, include but not limited to (1) diluent (also known as filler), such as starch, sucrose, dextrin, calcium carbonate, calcium sulfate, light magnesium oxide, microcrystalline cellulose, mannitol, lactose, pregelatinized Starch；(2) disintegrating agent, such as dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, gas-producing disintegrant etc.；(3) wetting agent, such as distilled water, ethanol etc.；(4) binding agent, such as Icing Sugar and syrup, starch slurry, polyvinylpyrrolidone, cellulose derivative, rubber cement, dextrin etc.；(5) lubricant, such as stearic acid, magnesium stearate, calcium stearate, micropowder silica gel, hydrogenated vegetable oil, Polyethylene Glycol；(6) filmogen, such as the natural materials such as pectin, agar, arabic gum, tragakanta, gelatin, the cellulose derivative such as carboxymethyl cellulose, hypromellose, the vinyl high molecular polymer such as polyvinyl alcohol, carbomer；(7) plasticizer, such as ethanol, propylene glycol, low molecular poly and O-phthalic ester etc.；And the coloring agent of necessity, aromatic and sweeting agent etc..

" weight portion " in description of the present invention, expression is that in described YIGUANJIAN, the consumption proportion of each Chinese crude drug is correlated with.According to practical situations, " 1 weight portion " of the present invention can be " 1g ", " 1kg " or other any weight.

The YIGUANJIAN provided by the invention purposes in treatment depression, it is preferred that embodiment includes:

1. raw material consist of Radix Glehniae 10 weight portion, Radix Ophiopogonis 10 weight portion, Radix Angelicae Sinensis 10 weight portion, Radix Rehmanniae 30 weight portion, Fructus Lycii 12 weight portion and Fructus Toosendan 5 weight portion YIGUANJIAN, add or be added without pharmaceutically acceptable adjuvant, prepare into acceptable preparation clinically, be used for treating depression.

2. raw material consist of Radix Glehniae 10 weight portion, Radix Ophiopogonis 10 weight portion, Radix Angelicae Sinensis 10 weight portion, Radix Rehmanniae 30 weight portion, Fructus Lycii 12 weight portion and Fructus Toosendan 5 weight portion YIGUANJIAN, and one or more in the above-mentioned chemical entities with antidepressant activity, add or be added without pharmaceutically acceptable adjuvant, prepare into acceptable preparation clinically, be used for treating depression.

3. raw material consist of Radix Glehniae 10 weight portion, Radix Ophiopogonis 10 weight portion, Radix Angelicae Sinensis 10 weight portion, Radix Rehmanniae 30 weight portion, Fructus Lycii 12 weight portion and Fructus Toosendan 5 weight portion YIGUANJIAN, add or be added without pharmaceutically acceptable adjuvant, prepare into acceptable preparation clinically, and with containing one or more the acceptable preparation clinically in the above-mentioned chemical entities with antidepressant activity, such asDeng, it is both or order gives patients with depression.

4. the consumption being grown up every day be raw material consist of Radix Glehniae 10g, Radix Ophiopogonis 10g, Radix Angelicae Sinensis 10g, Radix Rehmanniae 30g, Fructus Lycii 12g and Fructus Toosendan 5g YIGUANJIAN, add or be added without pharmaceutically acceptable adjuvant, the acceptable preparation clinically prepared.

Described in the following examples, the caused depressed mice of reserpine all shows as exception in every physical signs, as body temperature significantly reduce, related neurotransmitters (norepinephrine, dopamine and 5-hydroxy tryptamine) level in serum and cerebral tissue significantly reduces.YIGUANJIAN water decoction high dose (is daily measured with people quite) and can significantly be reversed above-mentioned abnormal physical signs, and effect is most and positive drug is suitable.Illustrate that YIGUANJIAN has good antidepressant effect, it is possible to provide new therapeutic choice for clinic.

Accompanying drawing explanation

Hereinafter, describe embodiment of the present invention in detail in conjunction with accompanying drawing, wherein:

Fig. 1 is illustrated that in embodiment 2 in each test group mice serum the measurement result of DA content.In figure, " * * " expression compares P < 0.01 with blank group；" ▲ ▲ " represent and compare P < 0.01 with model group.

Fig. 2 is illustrated that in embodiment 2 in each test group mice serum the measurement result of NE content.In figure, " * * " expression compares P < 0.01 with blank group；" ▲ ▲ " represent and compare P < 0.01 with model group.

Fig. 3 is illustrated that in embodiment 2 in each test group Hippocampus of Mice the measurement result of 5-HT content.In figure, " * * " expression compares P < 0.01 with blank group；" ▲ " represents compares P < 0.05 with model group, " ▲ ▲ " represent and compare P < 0.01 with model group.

Detailed description of the invention

Referring to specific embodiment, the present invention is described.It will be appreciated by those skilled in the art that these embodiments are merely to illustrate the present invention, its scope not limited the present invention in any way.

Experimental technique in following embodiment, if no special instructions, is conventional method.Medicinal raw material used in following embodiment, reagent material etc., if no special instructions, be commercially available purchase product.

Embodiment 1YIGUANJIAN water decoction

YIGUANJIAN raw material forms: (in the present embodiment, 1 weight portion=10g)

Radix Glehniae 100g, Radix Ophiopogonis 100g, Radix Angelicae Sinensis 100g, Radix Rehmanniae 300g, Fructus Lycii 120g, Fructus Toosendan 50g

Take each taste Chinese crude drug according to weight, add the water of medical material gross weight 10 times, soak 1 hour, be then heated to boiling, decoct 40 minutes, filtered while hot；Medicinal residues add the water of medical material gross weight 8 times, decoct 40 minutes, filtered while hot, merge twice filtrate, to obtain final product.

Embodiment 2The anti-reserpine of YIGUANJIAN 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, Hunan Si Laike Jing Da laboratory animal company limited provides, credit number: SCXK (Hunan) 2011-0003.

2. experimental drug

YIGUANJIAN: the YIGUANJIAN water decoction of embodiment 1 preparation

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), food-intake (10g/100g body weight d), drink water (changing weekly water 2～3 times).

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 (NaCl9g/L), gavage, 1ml/100g body weight sky

2. model group: with " blank group "

3. positive controls: Clomipramine Hydrochloride, 40mg kg^-1·d^-1

4. YIGUANJIAN high dose group: 23.04g crude drug kg^-1·d^-1

5. YIGUANJIAN low dose group: 11.52g crude drug kg^-1·d^-1

^*: described crude drug refers to the raw medicinal material gross weight of YIGUANJIAN

2. drug solution preparing:

1. the preparation of reserpine solution: dosage is 4mg kg^-1, taking 0.04g reserpine powder, use a small amount of physiological saline solution, be settled in 100ml volumetric flask, 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, weighs 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 high dose group medicinal liquid: the YIGUANJIAN water decoction of Example 1 preparation, normal pressure is concentrated into 501.3ml (namely every milliliter of medicinal liquid is containing 1.536g crude drug), seals after taking 1/3rd coolings, and 4 DEG C save backup.

5. the preparation of low dose group medicinal liquid: take remaining 2/3rds concentrated solutions, the distilled water of the volume that doubles, makes every milliliter of medicinal liquid containing 0.768g crude drug, seals, and 4 DEG C save backup.

4. dosage regimen

Each group gavage gives medicine or normal saline, every day 1 time, and (administration volume is all by 0.015mL g for successive administration 7d^-1·d^-1)；After last administration, except blank group, other respectively organizes lumbar injection 4mg kg^-1Reserpine, intraperitoneal injection volume presses 0.01mL g^-1·d^-1。

Experimentation and result:

1. the observation of temperature decline:

After last administration 4h, thermometer probe being inserted mice anal, the degree of depth is as the criterion completely into anus with thermometer probe, maintains at least 2min.Record each group of data, compare the difference of body temperature in administration group and matched group.Concrete outcome is 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,^▲▲Represent P < 0.01

Data analysis:

After model group mouse peritoneal injection reserpine, body temperature compares reduction highly significant (P < 0.01) with blank group, it was shown that reserpine causes depression model modeling success；Although the body temperature of the depressed mice of YIGUANJIAN high dose group rising compares with model group does not have significant difference, but the acting body that the high low dose group of YIGUANJIAN raises body temperature reveals dose-effect relationship.

2. NE (norepinephrine) in mice serum, the mensuration of 5-hydroxy tryptamine (5-HT) content in DA (dopamine) and cerebral tissue

8h after last is administered, plucks eyeball and takes blood, is stood 1 hour by taken blood, and centrifugal (3000r/min, 20min) takes supernatant and be placed in EP pipe, and cryopreservation is to be measured.After taking blood, sacrificed by decapitation animal, peels off brain on ice pan, removes cerebellum and olfactory bulb, retain remaining whole brain tissue, wrap up with masking foil ,-70 DEG C of preservations.Adding the homogenate of 9 times of PBS (PH7.4), make 10% brain tissue homogenate's liquid, inserted by homogenate in centrifuge tube, with 3000r/min centrifugation 20min under 4 DEG C of conditions, carefully collect supernatant after standing, be placed in 2mlEP pipe ,-70 DEG C of preservations are to be measured.

Adopt NE, DA in ELISA method detection mice serum and the content of cerebral tissue 5-HT.Result is in Table 2.

The assay result of neurotransmitter in table 2 mice serum and cerebral tissue

Data analysis:

1) in model group mice serum, DA content significantly reduces, and compares with blank group and has pole significant difference (P < 0.01), it was shown that reserpine causes depression model modeling success；Compare with model group, positive drug group and in YIGUANJIAN high and low dose group mice serum DA content all dramatically increase (P < 0.01), illustrate that YIGUANJIAN height low dosage all can significantly raise DA content in depressed mice serum.

2) in model group mice serum, NE content significantly reduces, and compares with blank group and has pole significant difference (P < 0.01), it was shown that reserpine causes depression model modeling success；Compare with model group, positive drug group and in each dosage group mice serum of YIGUANJIAN NE content all dramatically increase (P < 0.01).Illustrate that YIGUANJIAN has good effect in regulating internal NE and be horizontal.

3) in model group Mice brain tissues, 5-HT content significantly reduces, and compares with blank group and has pole significant difference (P < 0.01), it was shown that reserpine causes depression model modeling success；Compare with model group, positive drug group and in YIGUANJIAN high dose group Mice brain tissues 5-HT content all dramatically increase (respectively P < 0.01, P < 0.05).Illustrate that YIGUANJIAN high dose can significantly raise 5-HT content in depressed Mice brain tissues.

In a word, compare with model group, in YIGUANJIAN high group Mice Body, monoamine neurotransmitter DA, NE and 5-HT all significantly raise, wherein DA (P < 0.01), (NE (P < 0.01), 5-HT (P < 0.05), it was shown that it has good antidepressant effect.Through average ratio relatively, it is possible to find, YIGUANJIAN high dose increases monoamine transmitters effect in Mice Body and is better than low dosage.

Experiment conclusion

The caused depressed mice of reserpine all shows as exception in every physical signs, as body temperature significantly reduce, related neurotransmitters level in serum and cerebral tissue significantly reduces.YIGUANJIAN water decoction can reverse above-mentioned abnormal physical signs, and effect is most and positive drug is suitable.Having obvious action particularly in regulating the horizontal aspect of internal NE, prompting YIGUANJIAN can improve interest and the energy of depressive patient.

From overall data analysis, though YIGUANJIAN low dosage antidepressant effect inconspicuous, each index result of high dose group compares with depression model group and is respectively provided with significant.It is true that this high dose is converted by human body dosage every day.Therefore, namely YIGUANJIAN quantity is likely to the optimal dose of its antidepressant effect.

In a word, the invention provides YIGUANJIAN for treating the new medical usage of depression.Pharmacodynamics test shows, depression model animal is had significant curative effect by the pharmaceutical composition of the present invention, and effect is suitable with Clomipramine Hydrochloride.

Specific description of embodiments of the present invention above is not limiting as the present invention, and those skilled in the art can make various change or deformation according to the present invention, without departing from the spirit of the present invention, all should belong to scope of the following claims of the present invention.

Claims

1. YIGUANJIAN purposes in the medicine of preparation treatment depression；Wherein said YIGUANJIAN is made up of the Chinese crude drug of following weight portion:

2. purposes according to claim 1, it is characterised in that described medicine also includes the chemical entities with antidepressant activity.

3. purposes according to claim 2, it is characterized in that, described in there are one or more in tricyclic antidepressant, oxidase inhibitor, selective serotonin reuptake inhibitor, 5-hydroxytryptamine receptor antagonist, 5-hydroxy tryptamine cell reabsorption inhibitor, norepinephrine and dopamine cell reabsorption inhibitor and 5-hydroxy tryptamine and norepinephrine cell reabsorption inhibitor of the chemical entities of antidepressant activity；

Wherein, described tricyclic antidepressant is selected from one or more in imipramine, amitriptyline, Clomipramine, doxepin, desipramine, nortriptyline and protriptyline；

Described oxidase inhibitor is selected from one or more in phenelzine, isocarboxazid, tranylcypromine, moclobemide and brofaromine；

Described selective serotonin reuptake inhibitor is selected from one or more in citalopram, fluoxetine, fluvoxamine, paroxetine and Sertraline；

Described 5-hydroxy tryptamine cell reabsorption inhibitor is selected from trazodone；

Described norepinephrine and dopamine cell reabsorption inhibitor are selected from amfebutamone and/or nefazodone；

Described 5-hydroxy tryptamine and norepinephrine cell reabsorption inhibitor are selected from venlafaxine.

4. purposes according to any one of claim 1 to 3, it is characterised in that described medicine contains or do not contain pharmaceutically acceptable adjuvant.

5. purposes according to any one of claim 1 to 4, it is characterized in that, described medicine is oral formulations, one or more in decoct, powder, tablet, capsule, soft capsule, effervescent tablet, oral instant membrane, oral cavity disintegration tablet and oral liquid.