CN1234409C - Combinaton of medication for treating depression and preparation method - Google Patents
Combinaton of medication for treating depression and preparation method Download PDFInfo
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- CN1234409C CN1234409C CN200410034937.7A CN200410034937A CN1234409C CN 1234409 C CN1234409 C CN 1234409C CN 200410034937 A CN200410034937 A CN 200410034937A CN 1234409 C CN1234409 C CN 1234409C
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- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a medicinal composition for treating depression, which is composed of two active components of the following dosage: 3.5 to 14g of pachyman and 0.2 to 3.5g of ginger oil. The preparation method has the step that after the ginger oil is contracted by beta-cyclodextrin according to the weight proportion, the medicinal composition of PG is obtained. The composition is used for preparing medicine for treating depression, and has the advantages of stabile curative effect, high safety and reliability, simple process, easy production, etc.
Description
Patent application of the present invention is denomination of invention the dividing an application for " antidepressant composition and preparation method thereof " (application number 02138217.4) patent by JIUYUE in 2002 application on the 5th.
One, technical field:
The present invention relates to the composition and method of making the same and the medicinal usage of active ingredient of natural plant, particularly relate to the medicine that the preparation of compositions of pachyman and oil of ginger is become the treatment depression.
Two, background technology:
Depression refers to the affective disorders syndrome, and low with mental state is principal character.Clinical depressed mood, feeling of fatigue, anhedonia, thinking and the motion sluggishness of mainly showing as is with anxiety, sleep disorder, inappetence, despair and the vain hope etc. of committing suiside.Depression is the able-bodied commonly encountered diseases of the harm whole mankind, frequently-occurring disease.According to World Health Organization's psychosis popularity investigation report, whole world depression prevalence is up to 3~5%, and major depression patient homicide rate is up to 15~18%, and lifelong attack rate is up to 8~12% (men), 20~25% (woman).Clinically, normal and other serious disease of depression such as heart disease, apoplexy, cancer, immune disease etc. and deposit.Relevant depression is EPDML to be studies show that: along with the quickening of worldwide social industrialization, urbanization process, stressors increases greatly in the social life, the depression prevalence is in continuous rising, and ill crowd enlarges day by day, and wherein the morbidity in elderly population will be more outstanding.Depression will become one of main disease that the 21 century mankind face.
The seriousness of depression fashion trend and patient have caused the extensive attention of countries in the world because of the decline of psychological diathesis due to the mental disorder and the infringement of social function.The demand of antagonism down increases day by day in the world wide, and this quasi drugs world market sales volume is with the speed increment in every year 16.2% in recent years.The development of the control of depression and antidepressant new drug has become one of current international the world of medicine forward position hot research problem.
Depression cause of disease complexity, closely related with Physiological Psychology, not clear and definite yet so far.May with for a long time stress be relevant with cerebrum 5-hydroxytriptamine (5-HT), norepinephrine monoamine neurotransmitter metabolism such as (NE) and functional disorder that emotion causes, by excessive activation SAM (sympathetic adrenal-medullary) system, HPA (hypothalamic-pituitary-adrenocortical) system, link behavior and physiological effect that mediation is relevant with hormonal system and immune system.
The Western medicine of clinical treatment depression has multiple at present.Oxidase inhibitor (MAO-AI) (as moclobemide) is to the maincenter monoamine neurotransmitter inhibitory action of having degraded; 5-hydroxy tryptamine reuptake inhibitor (SSRI) (fluoxetine), then selectivity suppresses the 5-HT reuptake; And plain reuptake inhibitor (SNRI) (as venlafaxine) optionally suppresses 5-HT and NE heavily absorbs on 5-hydroxy tryptamine-noradrenaline; Dual function not only suppresses the reuptake of 5-HT but also block postsynaptic 5-HT in the antidepressants (as nefazodone) of 5-hydroxy tryptamine link
2Receptor; NE and DA reuptake inhibitor (as bupropin) selectivity suppress NE and DA reuptake.These medicines are limit because of itself effect characteristic mostly, have that the antidepressant spectrum is narrower, toxic and side effects is big, price is high, an easy shortcoming such as recurrence after the drug withdrawal.
Traditional Chinese medical science melancholia refers to the class disease that feelings will is peaceful, depression and stagnation of QI causes, with the depression of doctor trained in Western medicine many common parts is arranged.Chinese medicine contains the various active composition, can regulate each system on the whole, reaches the effect that safety is cured.Herba Sidae Rhombifoliae soup (Radix Bupleuri, Radix Scutellariae (processed with wine), Radix Codonopsis, Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens), Radix Glycyrrhizae, Rhizoma Zingiberis Recens, Fructus Jujubae), BANXIA HOUPU TANG (Rhizoma Pinelliae, Cortex Magnoliae Officinalis, Poria, Rhizoma Zingiberis Recens, Folium Perillae) and platinum diffusing (Alumen, Radix Curcumae, Rhizoma Anemones Altaicae, Zhu sand, artificial Calculus Bovis) treatment " globus hystericus ", depression, depressive psychosis have been reported successively; Hu Sirong is with forgetting melancholy soup (Magnetitum, Lapis Micae Aureus, Fructus Aurantii Immaturus, Cortex Phellodendri, the Rhizoma Pinelliae, Cortex Magnoliae Officinalis, Poria (processed with Cinnabaris), refreshing meat, Cortex Cinnamomi, Folium Perillae, Rhizoma Acori Graminei, Rhizoma Zingiberis Recens) treatment depression 470 examples according to one's conscience, and recovery from illness 70.2% takes a turn for the better 20.2%, total effective rate 90.4%; Zhao Zhisheng ' presses down and considers health ' the capsule for treating depression from intending Chinese medicine, and general curative effect is better than western medicine group; Human Shu Yu regulation of mental activities soup (Radix Bupleuri, Radix Curcumae, Rhizoma Acori Graminei, Fructus Aurantii Immaturus, Semen Persicae, Flos Carthami, Semen Platycladi, Radix Polygalae, DUANLONGMU, Radix Salviae Miltiorrhizae) such as Ma Yunzhi treatment apoplexy retarded depression disease, its cure rate is 39.06%, obvious effective rate is 30.40%, effective percentage is 21.09%, inefficiency is 9.45%, and obviously improves main and simultaneous phenomenon; The rugged wise man of Japan's tail finds that Xiao Jianzhong Tang (Ramulus Cinnamomi, Rhizoma Zingiberis Recens, Radix Paeoniae, Radix Glycyrrhizae, Fructus Jujubae, maltose end) has regulating action to depressive neurosis patient emotion; Research finds that also Radix Bupleuri adds Os Draconis Concha Ostreae soup (Radix Bupleuri, the Rhizoma Pinelliae, Ramulus Cinnamomi, Poria, Radix Scutellariae, Fructus Jujubae, Radix Ginseng, Concha Ostreae, Os Draconis, Rhizoma Zingiberis Recens) treatment effectiveness and shows fatigue, headache, nerve of plant symptom aspect there was no significant difference such as dizzy, stresses treatment depression, nervous.
The onset of above-mentioned Chinese medicine compound recipe is slow, and component more complicated, drug effect are remarkable inadequately, is difficult to formulate and implement the strict quality standard.
Poria is the dry sclerotia of Polyporaceae Poria cocos (Schw.) Wolf, and polysaccharide can account for the 80-93% of dry weight, is mainly β-pachyman etc." property of medicine opinion " record, Poria " appetizing, preventing or arresting vomiting is contrary, kind tranquilizing mind " has the effect of strengthening the spleen stomach function regulating, mind tranquilizing and the heart calming.Rhizoma Zingiberis Recens is the bright rhizome of Zingiberaceae Zingiber officinale Rosc, contains volatile oil 0.25-3.0%, and wherein main component is zingiberol, zingiberene, phellandrene, camphene etc." Treatise on Dietetic Therapy " record, Rhizoma Zingiberis Recens " non-return, it is unhappy to loose, appetizing gas ", pharmacological testing shows that pachyman has significant sedation and immunoloregulation function, and has antitumor action.6-zingiberene, 6-gingerol, 6-zingiberene alcohol are main component in the oil of ginger, have multiple effects such as central nervous system's inhibitory action and antioxidation, antitumor, antiinflammatory and protection gastric mucosa.
Three, summary of the invention:
1. goal of the invention
Purpose of the present invention is exactly in order to address the above problem, and a kind of composition and method of making the same that is prepared into by pachyman and two kinds of compositions of oil of ginger is provided, and the application in preparation treatment depression medicine.
2. technical scheme
Pharmaceutical composition of the present invention is characterized in that it is made up of the plant extract component of following weight proportion: pachyman 3.5-14g, oil of ginger 0.2-3.5g; The weight proportion of said extracted thing effective ingredient is pachyman 10.0g and oil of ginger 1.0g.
After each component is mixed can with the beta-schardinger dextrin-mixed in equal amounts, to increase the stability of compositions component.The consumption of beta-schardinger dextrin-also can change in proper range as the case may be.
Preparation of drug combination method of the present invention the steps include:
(1) Poria is behind water extraction, and adding 95% ethanol to concentration of alcohol in the concentrated solution is 50-80%, and the gained precipitation is pachyman;
(2) Rhizoma Zingiberis Recens supercritical CO
2Extraction, Petroleum ether extraction, vapor distillation or water boiling and extraction get oil of ginger;
(3) pachyman 3.5-14g, oil of ginger 0.2-3.5g promptly get compositions with mixing behind the beta-cyclodextrin inclusion compound oil of ginger.
In compositions, add an amount of adjuvant then, can be made into the oral formulations of tablet, granule or capsule.These dosage forms are to prepare according to those skilled in the art institute well-known process.The adjuvant that is used to make moulding processs such as tablet, granule, capsule is the auxiliary agent of using always, and for example starch, gelatin, arabic gum, Polyethylene Glycol etc. also have surfactant, lubricant, disintegrating agent, antiseptic, correctives, pigment etc. in addition.
3. beneficial effect
Advantage of the present invention is:
Resulting composition is formed succinct, and prescription is reasonable, and main active is clear and definite.The active component that extracts from two kinds of tuckahoes and Rhizoma Zingiberis Recens is formed the PG compositions by weight ratio.
(2) drug effect is remarkable, safe and reliable.Animal test results shows that said composition high and low dose group all can significantly reduce the absolute dead time of mice, shows that said composition has tangible antidepressant activity.
(3) technology is simple, is easy to suitability for industrialized production.From Poria and Rhizoma Zingiberis Recens, extract the method for active component simple and also only need by weight ratio component to be mixed when being prepared into compositions after can obtain, so preparation is simple, help industrial large-scale production.
Four, the specific embodiment:
The pharmaceutical composition of embodiment 1. treatment depressions
A kind of pharmaceutical composition for the treatment of depression is made up of pachyman 3.5-14g, oil of ginger 0.2-3.5g;
Embodiment 2 preparation of drug combination methods the steps include:
(1) get dry poria cocos sclerotium, with the water extraction of 10 times of volumes three times, merge extractive liquid,, adding 95% ethanol to concentration of alcohol after concentrating is 80%, and the gained precipitation is pachyman, and yield is 80.1%;
(2) get dry Rhizoma Zingiberis Recens, with conventional vapor extraction three times, yield is 1.0%.
(3) get pachyman 10g and oil of ginger 1g, behind the beta-cyclodextrin inclusion compound oil of ginger, mix promptly getting compositions PG.In above-mentioned composition PG, add an amount of starch, make tablet.
Embodiment 3 compositionss are to the influence of desperate model mice behavior
Animal model: experiment of mice forced swimming and mouse tail suspension swimming test
Animal: male mice in kunming, body weight 28 ± 2g, random packet.
Behind the gastric infusion 15 days, carry out behavioral experiment, measure the absolute dead time in the experiment of mice forced swimming and outstanding tail;
The compositions component sees Table 1 to mice forced swimming experiment and the exercising result that hangs the tail experiment.A minimizing that cardinal symptom is a motivational behavior of depression, forced swimming experiment and the struggle of hanging in the tail experiment are the motivational behaviors of animal, the absolute motionless absence of motivation state that then reflects animal passiveness in the experiment.Most of antidepressant drugs can increase the motivational behavior of animal subject, reduce the forced swimming experiment and hang absolute dead time in the tail experiment.Two dosage of positive drug fluoxetine height all can significantly reduce the absolute dead time of mice in the experiment of forced swimming and outstanding tail.The compositions high dose group all can significantly reduce the absolute dead time of mice in two experiments.The result shows that compositions has tangible antidepressant activity.
Table 1 compositions is to the influence of dead time in the desperate model of mice behavior (x ± s)
Group | Dosage (mg/kg) | The absolute dead time (s) | |
The forced swimming experiment | Outstanding tail experiment | ||
Blank fluoxetine PG | - 10 20 460 230 | 124.2±3.5 70.1±1.5 *** 31.6±2.1 *** 101.4±3.5 68.7±2.7 *** | 88.4±2.0 43.0±1.2 *** 25.2±1.1 *** 70.1±0.9 60.4±1.3 ** |
*P<0.05,
*P<0.01,
* *Compare with matched group P<0.001.
Claims (5)
1. pharmaceutical composition for the treatment of depression is characterized in that it is made up of the plant extract effective ingredient of following weight proportion:
Pachyman 3.5-14g, oil of ginger 0.2-3.5g.
2. pharmaceutical composition according to claim 1 is characterized in that the weight proportion of extract effective ingredient
For: pachyman 10g, oil of ginger 1.0g.
3. method for preparing the pharmaceutical composition of claim 1, its preparation methods steps is:
(1) Poria water extraction, gained extracting solution suitably concentrate, and adding 95% ethanol to extracting solution concentration of alcohol is 50-80%, and the gained precipitation is pachyman;
(2) Rhizoma Zingiberis Recens supercritical CO
2Extraction, Petroleum ether extraction, vapor extraction or water boiling and extraction promptly get oil of ginger;
(3), promptly get compositions with mixing behind the beta-cyclodextrin inclusion compound oil of ginger with pachyman 3.5-14g and oil of ginger 0.2-3.5g.
4. pharmaceutical composition according to claim 1 is characterized in that in compositions, adds an amount of adjuvant, can be made into tablet, the solid orally ingestible of granule and capsule with conventional preparation method.
5. the application of the described pharmaceutical composition of claim 1 in preparation treatment depression medicine.
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CN200410034937.7A CN1234409C (en) | 2002-09-05 | 2002-09-05 | Combinaton of medication for treating depression and preparation method |
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WO2006072213A1 (en) * | 2005-01-03 | 2006-07-13 | Hong Kong Jockey Club Institute Of Chinese Medicine Limited | Anti-depression formulations |
CN109315782A (en) * | 2017-08-01 | 2019-02-12 | 无限极(中国)有限公司 | It is a kind of to have effects that improve the composition of depressive anxiety and its application |
CN115501215A (en) * | 2022-07-14 | 2022-12-23 | 山东第一医科大学(山东省医学科学院) | Medicine for treating depression |
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