CN105055855A

CN105055855A - Traditional Chinese medicine composition having sleep improvement and immunity boost effects as well as preparation method and application of traditional Chinese medicine composition

Info

Publication number: CN105055855A
Application number: CN201510493746.5A
Authority: CN
Inventors: 叶华; 王恒斌; 李全; 孙翔; 祝倩倩; 罗年翠; 王亦周
Original assignee: LEIYUNSHANG PHARMACEUTICAL CO Ltd
Current assignee: LEIYUNSHANG PHARMACEUTICAL CO Ltd
Priority date: 2015-08-13
Filing date: 2015-08-13
Publication date: 2015-11-18
Anticipated expiration: 2035-08-13
Also published as: CN105055855B

Abstract

The invention discloses traditional Chinese medicine composition having sleep improvement and immunity boost effects as well as a preparation method and an application of the traditional Chinese medicine composition. The traditional Chinese medicine composition having the sleep improvement and immunity boost effects is prepared from Siberian ginseng, American ginseng, semen ziziphi spinosae, polygonatum, psoralea corylifolia and wolfiporia extensa. Animal function test results prove that the provided traditional Chinese medicine composition has the sleep improvement and immunity boost effects; animal safety test results prove that the traditional Chinese medicine composition is safe and has no toxic and side effects and no teratogenic and mutagenic actions. Human feeding trials prove that the traditional Chinese medicine composition can effectively improve symptoms such as insomnia, low immunity and the like, has significant effect, can be used for preparing drugs or health care products and has broad market prospects.

Description

There is the Chinese medicine composition and its preparation method and application of improving water flood, enhancing immunity effect

Technical field

The present invention relates to medicine or health product Chinese medicine composition field, be specifically related to a kind of Chinese medicine composition and preparation method thereof and the application with improving water flood, enhancing immunity effect.

Background technology

Sleep is a kind of spontaneous and reversible quiescent condition that higher vertebrate periodically occurs, the brief interruption that the reactivity that showing as body stimulates to external world reduces and realizes.The time in all one's life nearly 1/3 of people is spent in sleep.When people are in sleep state, the brain of people and health can be made to obtain having a rest, rest and reorganize and recovering, and appropriate sleep contributes to the daily working and learning of people.Science improves sleep quality, is the guarantee of the normal work and study life of people.Sleep disorder refers to the exception of amount of sleep and the exception of sleep matter, or when sleeping, some clinical symptoms occurs, as sleep reduces or hypersomnia, and somnambulance etc.Difficulty falling asleep, light sleep and festless sleep, wake up after have difficulty in going to sleep, dreaminess, the symptoms such as often low, the headache of, myasthenia of limbs, bradykinesia, work efficiency dispirited with daytime, hypomnesis.Poor sleep and insomnia make people unhappy, absent minded, have a strong impact on daily life and work, and chronic insomnia person can increase the risk of the disease such as hypertension and depression.

According to interrelated data display, the whole nation the current people of existing more than 50% have difficulty in going to sleep and phenomenon of having a sleepless night, and due to chronic insomnia, many people have suffered from many relevant diseases.Sleep disorder has become a large killer of the mankind, brings huge hidden danger to the life of people, work, study.At present, all kinds of improving water flood products that market is popular are mainly sedative hypnotics and melatonin class Chinese medicine composition.Sleeping pill conventional clinically at present has Benzodiazepines, barbiturates and other non-barbiturateses, the effectiveness comparison of its Cure for insomnia is obvious, but affect larger on its liver, kidney, user easily produces the dependency to medicine, usually continue to increase pharmaceutical dosage and could keep effect, but also very large toxic and side effects can be produced, be not therefore the medicine of applicable long-term taking.Melatonin improving water flood effect is still not clear, and long-term or high dose takes melatonin may produce harm, as obviously suppressed human reproductive system's function to human body.Person in middle and old age's (because melatonin secretion reduces), if crowd's melatonin daytime is residual comparatively large, has dizzy and walk and unstablely wait side effect, may give older, health comparatively weak person bring danger.

Insomnia, the traditional Chinese medical science is referred to as " being insomnia ", " insomnia ", " must not crouch ", " unable to close the eyes " etc.The traditional Chinese medical science thinks that insomnia card has deficiency and excess two kinds, is caused by the inherent QI and blood of body, visceral dysfunction.Therefore, the treatment of insomnia, should focus on the medical treatment of internal organs, and QI and blood is in harmonious proportion, equilibrium between yin and yang, function is attributed to normally.In conjunction with Chinese medical theory, it is imperative to develop from safety, the effectively Chinese medicine composition of improving water flood.

Immunity refers to that human immune system resists the ability of pathogenic infection.According to World Health Organization's investigation, the whole world about has the people of more than 35% to be in fatigue state, and especially middle-aged male crowd fatigue state person is up to 60-75%.With the quickening pace of modern life, people face each side pressure such as family, cause, society, often occur having a delicate constitution, the reduction of malnutrition, lethargy, fatigue and weak, appetite, the hypoimmunity performance such as sleep disorder.Slight immunocompromised, naturally recovered, and serious immunocompromised is not only needed the intervention of Drug therapy, even has the possibility causing canceration by the regulation machine physical ability of a period of time.

The traditional Chinese medical science think disease generation, develop and lapse to the growth and decline depending on good and evil, relevant with the immunologic function of body, thus propose the principle of mainly curing the disease of strengthening vital QI to eliminate pathogenic factors.Righting refers to helps body healthy energy, a kind of Therapeutic Principle of health invigorating, the anti-heresy of raising body, resistance against diseases.By strengthening the method for healthy energy, eliminating evilly to go out, situation of getting well.Chinese medicine is given prominence at the therapeutic effect of immunocompromised, can control, give full play to immunity of organisms according to the different Syndrome Differentiation of Constitution opinion of people.

Research display, immune system can obtain repairing to a certain degree between sleep period, and then plays regulatory role sleep." healthy physique is from sleep " is that medical researchers is according to the neodoxy drawn the latest result of sleep study.Extended sleep deficiency can bring a series of body injury, comprises that elaborative faculty goes down, vigilance power and judgment decline, immunologic hypofunction, endocrine regulation etc.Visible, there is very large contacting between sleep quality and immunity.

In sum, improving water flood and enhancing immunity have become the focus of growing interest, and researching and developing that one has can obviously improving water flood, enhancing immunity effect, and the Chinese medicine composition had no side effect again has great importance.

Summary of the invention

The object of the present invention is to provide a kind of Chinese medicine composition with improving water flood, enhancing immunity effect, it adopts pure natural plant to make, to human non-toxic's side effect, and can long-term taking.Another object of the present invention is to provide preparation method and the application thereof of this Chinese medicine composition.

Technical scheme, in order to realize above object, the technical scheme that the present invention takes is:

Have a Chinese medicine composition for improving water flood, enhancing immunity effect, it is made up of the crude drug of following portions by weight:

Radix Et Caulis Acanthopanacis Senticosi 2 ~ 10 parts, Radix Panacis Quinquefolii 1 ~ 10 part, Semen Ziziphi Spinosae 5 ~ 30 parts, Rhizoma Polygonati 5 ~ 20 parts, Fructus Psoraleae 1 ~ 10 part, 5 ~ 30 parts, Poria.

Preferably, the weight proportion of each crude drug is:

Radix Et Caulis Acanthopanacis Senticosi 4 ~ 8 parts, Radix Panacis Quinquefolii 2 ~ 8 parts, Semen Ziziphi Spinosae 10 ~ 20 parts, Rhizoma Polygonati 6 ~ 16 parts, Fructus Psoraleae 2 ~ 8 parts, 10 ~ 20 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 2 parts, Radix Panacis Quinquefolii 1 part, Semen Ziziphi Spinosae 10 parts, Rhizoma Polygonati 6 parts, Fructus Psoraleae 3 parts, 10 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 4 parts, Radix Panacis Quinquefolii 2 parts, Semen Ziziphi Spinosae 30 parts, Rhizoma Polygonati 10 parts, Fructus Psoraleae 8 parts, 30 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 4 parts, Radix Panacis Quinquefolii 8 parts, Semen Ziziphi Spinosae 20 parts, Rhizoma Polygonati 16 parts, Fructus Psoraleae 2 parts, 10 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 6 parts, Radix Panacis Quinquefolii 6 parts, Semen Ziziphi Spinosae 5 parts, Rhizoma Polygonati 5 parts, Fructus Psoraleae 7 parts, 5 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 8 parts, Radix Panacis Quinquefolii 2 parts, Semen Ziziphi Spinosae 15 parts, Rhizoma Polygonati 7 parts, Fructus Psoraleae 3 parts, 20 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 6 parts, Radix Panacis Quinquefolii 5 parts, Semen Ziziphi Spinosae 15 parts, Rhizoma Polygonati 11 parts, Fructus Psoraleae 5 parts, 15 parts, Poria.

The weight proportion of each crude drug is also preferred:

Radix Et Caulis Acanthopanacis Senticosi 5 parts, Radix Panacis Quinquefolii 5 parts, Semen Ziziphi Spinosae 11 parts, Rhizoma Polygonati 14 parts, Fructus Psoraleae 3 parts, 18 parts, Poria.

The Chinese medicine composition with improving water flood, enhancing immunity effect provided by the invention, can be prepared into oral liquid, granule, capsule, tablet, pill by each crude drug and extract thereof and acceptable carrier.

The present invention based on Traditional Chinese medical theory, with Radix Et Caulis Acanthopanacis Senticosi, Radix Panacis Quinquefolii, Semen Ziziphi Spinosae, Rhizoma Polygonati, Fructus Psoraleae, Poria for raw material.This product raw material is 2010 editions pharmacopeia and records kind, not at the row of " eighteen incompatible medicaments ", " nineteen medicaments of mutual restraint ", without incompatibility.Radix Et Caulis Acanthopanacis Senticosi belongs to the Qi-tonifying drug in tonic, has the effect of strengthening the body resistance, replenishing QI to invigorate the spleen, suppressing the hyperactive liver the kidney invigorating, intelligent promoting and the mind tranquilizing, beneficial able-bodied bone, blood circulation promoting and blood stasis dispelling; Radix Panacis Quinquefolii is famous and precious Chinese medicine, has boosting qi and nourishing yin, clearing away heat and promoting production of body fluid, adjust tonifying five ZANG-organs, the effect of relieving restlessness of calming the nerves; The two is combined into monarch drug.Semen Ziziphi Spinosae is sweet flat with its nature and flavor, enters the warp of conscience, has the tonifying liver that nourishes blood, the effect of mind tranquilizing and the heart calming; Rhizoma Polygonati has invigorating the spleen and replenishing QI, yin nourishing, spleen invigorating, lung moistening, the effect of kidney tonifying; The two is ministerial drug; Fructus Psoraleae benefiting kidney-essence, warming the kidney to activate YANG; Poria has mind tranquilizing and the heart calming, the effect of spleen invigorating; The two is adjuvant.The each material combination of this product, complements each other, and jointly reaches effect of improving water flood, enhancing immunity.

The preparation method of Chinese medicine composition of the present invention, it comprises following processing step:

A, by weight, get Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add ethanol, heating and refluxing extraction, obtain ethanol extract;

B, get steps A ethanol extraction after medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add water, heating extraction, obtain aqueous extract;

C, be concentrated into without ethanol taste by steps A ethanol extract, step B Aqueous extracts concentrates, and merges to obtain concentrate;

D, step C gained concentrate and pharmaceutically acceptable carrier are made preparation.

Preferably, the above-described preparation method of Chinese medicine composition with improving water flood, enhancing immunity effect, is characterized in that, comprise the following steps:

A, get Radix Panacis Quinquefolii by weight, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 10 ~ 90% ethanol (volumetric concentration for) of the volume of medical material weight 1 ~ 10 times amount, heating and refluxing extraction 1 ~ 3 time, each 1 ~ 3 hour, merges to obtain alcohol extract; Ethanol reclaims;

B, get Semen Ziziphi Spinosae, Rhizoma Polygonati, the Poria of the medicinal residues after steps A ethanol extraction and parts by weight, add the water of 1 ~ 15 medical material times amount, heating extraction 1-3 time, each 1 ~ 3 hour, merge to obtain aqueous extract;

C, steps A alcohol extract to be concentrated into medical material equivalent be that 0.8:1 ~ 2:1, step B Aqueous extracts is concentrated into medical material equivalent and is about 0.8:1 ~ 2:1, and mixing, continues to be concentrated into medical material equivalent and be about 1:1 ~ 2:1;

D, by step C gained concentrate and chitosan, xylitol, sucralose, dextrin and starch one or more combination, make oral liquid, granule, capsule, tablet or pill.

As more preferably scheme, the above-described preparation method of Chinese medicine composition with improving water flood, enhancing immunity effect, it comprises the following steps:

A: get Radix Panacis Quinquefolii by weight, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, the volumetric concentration adding medical material gross weight 5 times of volumes is 50% ethanol, and heating and refluxing extraction 2 times each 2 hours, merges to obtain alcohol extract;

B: alcohol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add the water of 10 times amount, heating decocts extraction 2 times, each 2 hours, merges to obtain aqueous extract;

C: be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 1:1, and Aqueous extracts is concentrated into medical material equivalent and is about 1:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 1.5:1.

Beneficial effect: provided by the invention there is improving water flood, compared to the prior art the Chinese medicine composition and preparation method thereof of enhancing immunity effect have the following advantages:

The theory that the present invention controls according to Chinese herb decoction opinion, preferably obtained the Chinese medicine composition of best prescription proportioning by great many of experiments, Chinese medicine composition medication is rigorous, and proportioning is scientific and reasonable.

The present invention, according to the physicochemical property of each flavour of a drug, filters out best extraction separation method by great many of experiments, and extraction process is reasonable, workable, and extract the active constituent content obtained high, impurity is few.

Chinese medicine composition provided by the invention shows through the pharmacological results, can obviously improving water flood and enhancing immunity effect, and long-term taking, have no side effect.

Improving water flood function test: give mice one month with Chinese medicine composition oral liquid 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d of the present invention tri-dosage groups, carries out direct sleep experiments, extends the pentobarbital sodium experiment length of one's sleep, pentobarbital sodium sub-threshold dose sleep experiments, barbital sodium Sleep latency are tested.Result shows that Chinese medicine composition oral liquid 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group of the present invention all acts on without direct sleep mice.3.0ml/kg/d group mouse sleep time is longer than 0ml/kg/d group, and mice sleep is significantly shorter than 0ml/kg/d group incubation period, all has statistical significance (P < 0.05) with 0ml/kg/d group comparing difference.Result according to the improving water flood function test of " health food inspection and assessment technical specification " judges, Chinese medicine composition of the present invention has improving water flood function.

Enhancing immunity function test: give mice one month with Chinese medicine composition oral liquid 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d of the present invention tri-dosage group per os, carry out mouse cell immunologic function, humoral immune function, monocytes/macrophages function and NK cytoactive detection, result display 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group adds ConA hole and the difference not adding ConA hole absorbance, and the weightening finish of 3.0ml/kg/d group auricular concha is all higher than 0ml/kg/d group; 3.0ml/kg/d group half hemolysis value, hemolysis plaque number are higher than 0ml/kg/d group; 3.0ml/kg/d group NK cytoactive is higher than 0ml/kg/d group, and difference has statistical significance (P < 0.05).Result according to the enhancing immunity function test of " health food inspection and assessment technical specification " judges, Chinese medicine composition of the present invention has enhancing immunity function.

Acute oral toxicity test and 30 days feeding trials: Chinese medicine composition provided by the invention is female, male mice acute oral MTD is greater than 22400mg/kg, and according to acute toxicity dose grading standard, Chinese medicine composition of the present invention belongs to nontoxic level.

Chinese medicine composition of the present invention gives rat 30 days with the dosage of 3.0mg/kg/d, 6.5mg/kg/d, 10.0mg/kg/d (being equivalent to 30 times of human body recommended dose, 65 times, 100 times), animal subject ordinary circumstance is good, the change all without exception of body weight, food utilization, organ weights, organ coefficient; Hematological indices and the display of biochemical indicator result, indices is all in normal range; Each internal organs histopathologic examination is showed no the pathological change relevant with given the test agent, according to 30 days feeding trials of Ministry of Public Health " health food inspection and assessment technical specification " (version in 2003), give the Chinese medicine composition of the present invention of animal human body recommended dose 100 times, do not observe illeffects.

Teratogenesis mutagenicity test: experimental result shows that Chinese medicine composition of the present invention each dosage group Salmonella reversion test, mouse marrow cell micro nuclear test and mouse inbred strain result are feminine gender, illustrate that Chinese medicine composition of the present invention is without teratogenesis mutagenic action, safe and reliable.

The present invention has also carried out Chinese medicine composition improving water flood and enhancing immunity human feeding trial, improving water flood result of the test shows, self compare before and after the test-meal of test-meal group and compare between matched group group, clinical symptoms integration obviously reduces (P < 0.01), test-meal group crowd sleep quality obviously improves, and do not report other side effect, Chinese medicine composition of the present invention is improved the function of sleep.Enhancing immunity result of the test shows, before and after the test-meal of test-meal group, the content of lymphocyte and macrophage obviously increases (P < 0.01), apparently higher than matched group, compare between two groups and have significant difference (P < 0.01), illustrate that this invention Chinese medicine composition has the function of enhancing human body immunity power.

Detailed description of the invention

Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.After having read the present invention, the amendment of those skilled in the art to various unsubstantiality of the present invention has all fallen within the application's claims limited range.

Embodiment 1

Chinese medicine composition oral liquid of the present invention

1, raw material weight number

2, preparation process

(1) get described Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 50% ethanol (volumetric concentration) of medical material weight 5 times amount, heating and refluxing extraction 2 times, each 2 hours, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 10 times amount, heating decocts extraction 2 times, each 2 hours, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 1:1, and Aqueous extracts is concentrated into medical material equivalent and is about 0.8:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 1:1.

(4) chitosan is made into 1% aqueous solution, medicine liquid heating to 60 DEG C, adds chitosan liquid while stirring, stir 30 minutes, centrifugal, obtain clear liquor.

(5) xylitol, sucralose purified water are dissolved, add in clear liquor, purified water is settled to amount of preparation, adjusts PH to 6.0-5 DEG C of cold preservation leaves standstill 24 hours, and 0.45 μm of filtering with microporous membrane, obtains oral liquid of the present invention.

Embodiment 2

Chinese medicinal composition granules of the present invention

1, raw material weight number

2, preparation process

(1) get above-mentioned Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 60% ethanol of medical material weight 8 times amount, heating and refluxing extraction 2 times, each 1 hour, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 8 times amount, heating decocts extraction 2 times, each 1 hour, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 0.8:1, and Aqueous extracts is concentrated into medical material equivalent and is about 0.8:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 1:1.

(4) concentrated solution is added dextrin, starch, mix homogeneously, granulate, dry, make granule.

Embodiment 3

Chinese medicinal composition capsules agent of the present invention

1, raw material weight number

2, preparation process

(1) get above-mentioned Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 80% ethanol of total medical material weight 10 times amount, heating and refluxing extraction 2 times, each 2 hours, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 5 times amount, heating extraction 2 times, each 2 hours, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 1:1, and Aqueous extracts is concentrated into medical material equivalent and is about 1:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 2:1.

(4) above-mentioned concentrated solution and starch, dextrin are mixed, make paste block, dry, add starch appropriate, be ground into fine powder, sieve, mixing, with the general one-tenth ball of water, encapsulated.

Embodiment 4

Chinese medicine composition tablet of the present invention

1, raw material weight number

2, preparation process

(1) get above-mentioned Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 70% ethanol of medical material weight 3 times of volumes, heating and refluxing extraction 3 times, each 1 hour, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 6 times amount, heating extraction 3 times, each 1 hour, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 2:1, and Aqueous extracts is concentrated into medical material equivalent and is about 1:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 1.5:1.

(4) concentrated solution is added dextrin, starch, mix homogeneously, granulate, dry, tabletting, makes tablet.

Embodiment 5

Chinese medicine composition pill of the present invention

1, raw material weight number

2, preparation process

(1) get above-mentioned Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 90% ethanol of medical material weight 3 times of volumes, heating and refluxing extraction 3 times, each 1 hour, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add medical material weight 6 times of volumes, heating decocts extraction 3 times, each 1 hour, merges to obtain aqueous extract;

(3) step (1) ethanol extract is concentrated into without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 2:1, Aqueous extracts is concentrated into medical material equivalent and is about 1.5:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 2:1.

(4) concentrated solution is added appropriate dextrin, mix homogeneously, dry, close with 85% ethanol and stick together, mould and make ball, drying, active carbon coating and get final product.

Embodiment 6

Chinese medicine composition oral liquid of the present invention

1, raw material weight number

2, preparation process

(1) get described Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 50% ethanol (volumetric concentration) of medical material weight 7 times amount, heating and refluxing extraction 2 times, each 1.5 hours, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 12 times amount, heating decocts extraction 2 times, each 1.5 hours, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 1.5:1, and Aqueous extracts is concentrated into medical material equivalent and is about 2:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 2:1.

(5) xylitol, sucralose purified water are dissolved, add in clear liquor, purified water is settled to amount of preparation, adjusts PH to 5.0-5 DEG C of cold preservation leaves standstill 24 hours, and 0.45 μm of filtering with microporous membrane, obtains oral liquid of the present invention.

Embodiment 7

Chinese medicinal composition granules of the present invention

1, raw material weight number

2, preparation process

(1) get above-mentioned Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 60% ethanol of medical material weight 5 times amount, heating and refluxing extraction 2 times, each 2 hours, merge to obtain alcohol extract; Ethanol reclaims;

(2) get the water that step (1) ethanol extraction medicinal residues and Semen Ziziphi Spinosae, Rhizoma Polygonati, Poria add 14 times amount, heating decocts extraction 2 times, each 1 hour, merges to obtain aqueous extract;

(3) be concentrated into by alcohol extract without ethanol taste, medical material equivalent (relative alcohol extraction part) is about 1:1, and Aqueous extracts is concentrated into medical material equivalent and is about 1:1, mixes with alcohol extraction concentrated solution, continues to be concentrated into medical material equivalent and is about 1.5:1.

Effect example 1

Chinese medicine composition improving water flood function test of the present invention

1 materials and methods

1.1 samples: the oral liquid that the embodiment of the present invention 1 prepares, specification: 30ml/ props up, lot number: 20141001 sample morphology are brown color liquid, puts shady and cool dry ventilation and preserves.

1.2 laboratory animals: select SPF level CI/F1 that Shanghai western pul-Bi Kai laboratory animal company limited breeds for Healthy female mice 120, body weight 19.0-21.9g, laboratory animal production licence number is SCXK (Shanghai) 2013-0016, the quality certification number: 2008001643010.

Mice conforms, and (temperature is 20-25 DEG C, relative humidity is 40-70%), quarantine and be divided into three large group at random by body weight after 4 days, wherein I group of mice 40, be divided into 4 dosage groups at random, often organize 10, first carry out direct sleep experiments, carry out the experiment length of one's sleep of prolongation pentobarbital sodium next day again; II group of mice 40, is divided into 4 dosage groups at random, often organizes 10, carries out pentobarbital sodium sub-threshold dose hypnosis experiment; III group of mice 40, is divided into 4 dosage groups at random, often organizes 10, carries out the experiment of barbital sodium Sleep latency.

1.3 dosage choice and tested material give mode: establish 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d tri-dosage groups (being equivalent to 5 times of given the test agent human body recommended intake, 10 times, 30 times respectively), separately establish 0ml/kg/d group to replace tested material with sterilized water.Given the test agent sterilized water is prepared, and basic, normal, high dosage formulation concentration is respectively 5%, 10%, 30%, and per os gives the tested material of mice corresponding dosage once a day, and mouse stomach dosage is 0.1ml/10g.

1.4 key instruments and reagent

1.4.1 key instrument: T1000 type electronic balance, JA2003 type electronic balance, electronic stopclock.

1.4.2 main agents: pentobarbital sodium, barbital sodium.

1.5 test method

Carry out according to the improving water flood functional check method of " health food inspection and assessment technical specification " (version in 2003).

1.5.1 the direct sleep experiments of mice

The continuous gavage of each dosage treated animal one month, after last administration, with mice righting reflex loss 1min for entering sleep, righting reflex recovers to be mice awakening criterion, records each group of sleep number of animals and the length of one's sleep.

1.5.2 the pentobarbital sodium experiment length of one's sleep is extended

The continuous gavage of each dosage treated animal one month, after last administration 15min, each treated animal presses 40mg/kg dosage lumbar injection pentobarbital sodium, and injection volume is 10mg/kg, right disappearance 1min for sleep index with mice, observe given the test agent and can extend pentobarbital sodium length of one's sleep.Difference between comparative control group and experimental group extend the length of one's sleep, the length of one's sleep, prolongation had significance, then experimental result is positive.

1.5.3 pentobarbital sodium sub-threshold dose hypnosis experiment

The continuous gavage of each dosage treated animal one month, after last administration 15min, each treated animal presses 35mg/kg dosage lumbar injection pentobarbital sodium, and injection volume is 10ml/kg, right disappearance 1min for sleep index with mice, record to group sleep number of animals each in pentobarbital sodium 30min.Difference between comparative control group and experimental group sleep number of animals, the increase of sleep animal incidence rate has significance, then experimental result is positive.

1.5.4 barbital sodium Sleep latency is tested

The continuous gavage of each dosage treated animal one month, after last administration 15min, each treated animal presses 300mg/kg dosage lumbar injection barbital sodium, and injection volume is 10ml/kg, right disappearance 1min for sleep index with mice, observe given the test agent to the impact of barbital sodium Sleep latency.Difference between comparative control group and experimental group Sleep latency, Sleep latency shortens significance, then experimental result is positive.

1.6 test data statistics: homogeneity test of variance is carried out to each test initial data with SPSS16.0 software, meet the data information that variance requires together, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group; Suitable variable transitions is carried out to the data information of nonnormal distribution or heterogeneity of variance, after meeting normal state or variance and requiring together, carries out statistical disposition by the data of conversion gained.

2 results

In experimentation, drinking water for animals is ingested normally, and outward appearance is without exception.

The impact of 2.1 Chinese medicine composition Oral Liquid On Mice body weight of the present invention

From table 1-1 to table 1-3, original body mass 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group of mice compares with 0ml/kg/d group, and there are no significant for difference (P > 0.05).Show that the original body mass of mice is comparatively balanced between each group.

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, each dosage group body weight and weight gain are through homogeneity test of variance, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between experimental group multiple in one factor analysis of variance method and a matched group.0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group compares with 0ml/kg/d, the equal not statistically significant of difference (P > 0.05).

Table 1-1 Chinese medicine composition oral liquid of the present invention is on the impact of I group of Mouse Weight

Table 1-2 Chinese medicine composition oral liquid of the present invention is on the impact of II group of Mouse Weight

Table 1-3 Chinese medicine composition oral liquid of the present invention is on the impact of III group of Mouse Weight

The impact that 2.2 Chinese medicine composition Oral Liquid On Mices of the present invention are directly slept

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, and after last administration, phenomenon of sleeping all does not occur each group mice.From table 2, Chinese medicine composition oral liquid 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group of the present invention all acts on without direct sleep mice.

The impact that table 2 Chinese medicine composition Oral Liquid On Mice of the present invention is directly slept

2.3 Chinese medicine composition oral liquids of the present invention are on the impact extending the pentobarbital sodium inducing mouse length of one's sleep

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, lumbar injection pentobarbital sodium, observes the length of one's sleep of mice.From table 3 result, 3.0ml/kg/d group mouse sleep time is significantly longer than 0ml/kg/d group (P < 0.05).

Table 3 Chinese medicine composition oral liquid of the present invention is on the impact extending the pentobarbital sodium inducing mouse length of one's sleep

2.4 Chinese medicine composition oral liquids of the present invention are on the impact of pentobarbital sodium sub-threshold dose hypnosis

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, lumbar injection pentobarbital sodium, observes each group mice sleep incidence rate in 30min.From table 4 result, 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d treated animal sleep incidence rate compares with 0ml/kg/d group, and 3.0ml/kg/d treated animal sleep incidence rate increases.

Table 4 Chinese medicine composition oral liquid of the present invention is on the impact of pentobarbital sodium sub-threshold dose inducing mouse sleep incidence rate

2.5 Chinese medicine composition oral liquids of the present invention are on the impact of barbital sodium Sleep latency

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, lumbar injection barbital sodium, observes the Sleep latency of mice.From table 5,3.0ml/kg/d group mice sleep is significantly shorter than 0ml/kg/d group (P < 0.05) incubation period.

Table 5 Chinese medicine composition oral liquid of the present invention is on the impact of barbital sodium Sleep latency

Result according to the improving water flood function test of " health food inspection and assessment technical specification " judges, Chinese medicine composition of the present invention has improving water flood function.

Effect example 2

Chinese medicine composition enhancing immunity function test of the present invention

1 materials and methods

1.1 samples: the embodiment of the present invention 1 gained oral liquid.Sample morphology is brown color liquid, puts shady and cool dry ventilation and preserves.

1.2 laboratory animals: select SPF level CI/F1 that Shanghai western pul-Bi Kai laboratory animal company limited breeds for Healthy female mice 200, body weight 18.6-21.3g, laboratory animal production licence number is SCXK (Shanghai) 2013-0016, the quality certification number: 2008001644438.

Mice is divided into I, II, III, IV, V 5 large group at random by body weight, and every large group 40 mices, are divided into 4 dosage groups, each dosage group 10.The mouse spleen lymphocyte that wherein I group of mice carries out ConA induction transforms, NK cell activity assays; II group of mice carries out auricle edema test; III group of mice carries out antibody-producting cell and detects and half hemolysis value HC ₅₀mensuration; IV group of mice carries out the test of mice carbonic clearance; V group of mice carries out Turnover of Mouse Peritoneal Macrophages and engulfs chicken red blood cell test.Raising temperature is 20-25 DEG C, and relative humidity is 40-70%

1.3 dosage choice and tested material give mode: establish 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d tri-dosage groups (being equivalent to 5 times of given the test agent human body recommended intake, 10 times, 30 times respectively), separately establish 0ml/kg/d group to replace tested material with sterilized water.Given the test agent sterilized water is prepared, and basic, normal, high dosage formulation concentration is respectively 5%, 10%, 30%, and per os gives the tested material of mice corresponding dosage once a day, and mouse stomach dosage is 0.1ml/10g.Continuous gavage measures every enhancing immunity functional parameter after one month.

1.4 key instruments and reagent

1.4.1 key instrument: card punch, T1000 type electronic balance, JA2003 type electronic balance, SG-603 Biohazard Safety Equipment, multi-functional microplate reader, CO2 gas incubator, JJ-100 electronic balance.

1.4.2 main agents: DNFB, SRBC, guinea pig serum, india ink, RPMI1640, ConA, MTT, isopropyl alcohol, SA buffer, Dou Shi reagent, YAC-1 cell, LDH matrix liquid.

1.5 test methods: carry out according to the enhancing immunity functional check method of " health food inspection and assessment technical specification " (version in 2003).Carry out 1. ConA inducing mouse Splenic vein hemodynamics test-mtt assay respectively; 2. DNFB inducing mouse delayed allergy (DTH)-ear swelling method; 3. antibody-producting cell detects-Jerne and improves slide method; 4. serum hemolysin mensuration-half hemolysis value (HC ₅₀); 5. mice carbonic clearance test; 6. Turnover of Mouse Peritoneal Macrophages engulfs chicken red blood cell test-half intracorporal method; 7. NK cytoactive detection-determination of lactate dehydrogenase method.

1.7 results judge: according to " health food inspection and assessment technical specification ", in cellular immune function, (mouse spleen lymphocyte of ConA induction transforms, DNFB inducing mouse DTH), any two aspect results of humoral immune function (antibody-producting cell detect, Turnover of Mouse Peritoneal Macrophages engulf chicken red blood cell), NK cytoactive four aspects are positive, can judge that this given the test agent has enhancing immunity function.

Two result of the tests wherein in cellular immune function assay project are the positive, or two dosage group results of any one test are positive, can judge that cellular immune function assay result is positive.In humoral immune function measurement result, two result of the tests are the positive, or two dosage group results of any one test are positive, can judge that humoral immune function measurement result is positive.In mononuclear phagocyte functional examination result, two result of the tests are the positive, or two dosage group results of any one test are positive, can judge that mononuclear phagocyte functional examination result is positive.More than one dosage group result of NK cytoactive detection test is positive, can judge that NK cytoactive result is positive.

2 results

From table 6-1 to table 6-5, original body mass 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group of mice compares with 0ml/kg/d group, no significant difference (P > 0.05).Show that the original body mass of mice is comparatively balanced between each group.

Per os gives the Chinese medicine composition oral liquid of the present invention month of mice various dose, by each dosage group body weight and weight gain value through homogeneity test of variance, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group compares with 0ml/kg/d, no significant difference (P > 0.05).

The impact of table 6-1 Chinese medicine composition Oral Liquid On Mice of the present invention body weight

The impact of table 6-2 Chinese medicine composition Oral Liquid On Mice of the present invention body weight

The impact of table 6-3 Chinese medicine composition Oral Liquid On Mice of the present invention body weight

The impact of table 6-4 Chinese medicine composition Oral Liquid On Mice of the present invention body weight

The impact of table 6-5 Chinese medicine composition Oral Liquid On Mice of the present invention body weight

The impact of 2.2 Chinese medicine composition Oral Liquid On Mice thymus of the present invention, spleen organ

Per os gave the embodiment of the present invention 1 Chinese medicine composition oral liquid of mice various dose after one month, thymus and the spleen of getting mice are weighed, calculate dirty body ratio, and homogeneity test of variance is carried out to dirty body ratio, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 7 result, 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group thymus body ratio and spleen body compare than with 0ml/kg/d group, all have increase.

The impact of table 7 Chinese medicine composition Oral Liquid On Mice of the present invention thymus, spleen organ

The impact that the mouse spleen lymphocyte that 2.3 Chinese medicine composition oral liquids of the present invention are induced ConA transforms

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, the mouse spleen lymphocyte transformation experiment of ConA induction is carried out with mtt assay, calculate and add ConA hole and the difference not adding ConA hole absorbance, and homogeneity test of variance is carried out to it, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 8 result, 1.0ml/kg/d, 3.0ml/kg/d group ConA hole with do not add ConA hole absorbance difference and compare higher than 0ml/kg/d group, difference has statistical significance (P < 0.05).

The impact of table 8 Chinese medicine composition Oral Liquid On Mice of the present invention Splenic vein hemodynamics

2.4 Chinese medicine composition oral liquids of the present invention are on the impact of DNFB inducing mouse DTH

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, carry out DNFB inducing mouse DTH by ear swelling method to test, calculating auricular concha increases weight, and homogeneity test of variance is carried out to it, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 9 result, the weightening finish of 3.0ml/kg/d group auricular concha is compared higher than 0ml/kg/d group, and difference has statistical significance (P < 0.05).

Table 9 Chinese medicine composition oral liquid of the present invention is on the impact of DNFB inducing mouse DTH

The impact of 2.5 Chinese medicine composition Oral Liquid On Mice antibody-producting cells (hemolysis plaque number) of the present invention

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, improve slide method with Jerne and carry out the experiment of mouse antibodies cellulation, calculate hemolysis plaque number, and homogeneity test of variance is carried out to it, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 10 result, 3.0ml/kg/d group hemolysis plaque number compares higher than 0ml/kg/d group, and difference has statistical significance (P < 0.05).

The impact of table 10 Chinese medicine composition Oral Liquid On Mice of the present invention hemolysis plaque number

2.6 Chinese medicine composition Oral Liquid On Mice half hemolytic dose (HC of the present invention ₅₀) impact

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, measured the half hemolytic dose (HC of mice by half hemolysis value method ₅₀), and homogeneity test of variance is carried out to it, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 11 result, 3.0ml/kg/d group mice serum half hemolysis value (HC ₅₀) compare higher than 0ml/kg/d group, difference has statistical significance (P < 0.05).

Table 11 Chinese medicine composition Oral Liquid On Mice of the present invention HC ₅₀impact

The impact of 2.7 Chinese medicine composition Oral Liquid On Mice carbonic clearance abilities of the present invention

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, carry out the experiment of mice carbonic clearance, calculate phagocytic index a, and homogeneity test of variance is carried out to it, meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 12 result, 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group mice phagocytic index a and 0ml/kg/d organizes more all to have and increases.

The impact of table 12 Chinese medicine composition Oral Liquid On Mice of the present invention carbonic clearance ability

2.8 Chinese medicine composition Oral Liquid On Mice peritoneal macrophages of the present invention engulf the phagocytic percentage of chicken red blood cell and the impact of phagocytic index

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, carried out Turnover of Mouse Peritoneal Macrophages and engulfed chicken red blood cell experiment, calculate phagocytic index and phagocytic percentage with half intracorporal method, and by phagocytic percentage through sin ^-1p ^1/2(P is phagocytic percentage, decimally represent) transform after carry out homogeneity test of variance, phagocytic index and phagocytic percentage meet homogeneity of variance requirement, carry out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 13 result, 0.5ml/kg/d, 1.0ml/kg/d, 3.0ml/kg/d group Turnover of Mouse Peritoneal Macrophages engulfs the phagocytic percentage of chicken red blood cell and phagocytic index compares with 0ml/kg/d group, all has increase.

Table 13 Chinese medicine composition Oral Liquid On Mice of the present invention peritoneal macrophage engulfs the impact of chicken red blood cell phagocytic rate and phagocytic index

The impact of 2.9 Chinese medicine composition Oral Liquid On Mice NK cytoactives of the present invention

Per os gave the Chinese medicine composition oral liquid of the present invention of mice various dose after one month, carried out NK cells in mice determination of activity, by NK cytoactive through sin with lactic dehydrogenase enzyme process ^-1p ^1/2(P is NK cytoactive, represents decimally) carries out homogeneity test of variance after transforming, and meets homogeneity of variance requirement, carries out statistical disposition with the comparative approach between two of mean between test group multiple in one factor analysis of variance method and a matched group.From table 14 result, 3.0ml/kg/d group NK cytoactive compares higher than 0ml/kg/d group, and difference has statistical significance (P < 0.05).

The impact of table 14 Chinese medicine composition Oral Liquid On Mice of the present invention NK cytoactive

Result according to the enhancing immunity function test of " health food inspection and assessment technical specification " judges, Chinese medicine composition of the present invention has enhancing immunity function.

Effect example 3

Chinese medicine composition safety testing of the present invention

1 materials and methods

1.1 samples: the embodiment of the present invention 3 gained capsule, specification: 0.5g/ grain, lot number: 20131006.Sample morphology is brown color liquid, puts shady and cool dry ventilation and preserves.

1.2 laboratory animals: cleaning grade healthy adult ICR mice, male and female half and half, the weight of animals is female is 18.5-20.9g, is provided by Yangzhou University's comparative medicine center, production licence number SCXK (Soviet Union) 2012-0004, the quality certification number: 0025266.The healthy weanling rat of cleaning grade, male and female half and half, are provided by Shanghai Slac Experimental Animal Co., Ltd., production licence number SCXK (Soviet Union) 2012-0002, the quality certification number: 2007000570051.Experimental animal feeding temperature is 20-25 DEG C, and relative humidity is 40-70%

1.3 key instruments: T-1000 type electronic balance, JJ-100 type electronic balance, JA-2003 electronic balance, AL104 type electronic balance, centrifuge, OLYMPUS microscope, Hitachi 7100 type automatic clinical chemistry analyzer, BAKERSG-603 Biohazard Safety Equipment, electro-heating standing-temperature cultivator, SX-700 autoclave, KYC-100C type constant-temperature table, SIEMENSADVIA2120i blood analyser.Salmonella typhimurium saltant TA97, TA98, TA100, TA102 derive from HSPH of Fudan University; S-9 derives from HSPH of Fudan University.

1.4 experimental technique

1.4.1 acute toxicity test in mice: carry out acute toxicity test in mice by maximum tolerated dose method

1.4.2 rat 30 days feeding trials: each treated animal gives after normal feedstuff feeds 30 days continuously, fasting overnight, by only weighing, 10% chloral hydrate presses 3.5ml/kg intraperitoneal injection of anesthesia, get its hematological indices and blood parameters through ventral aorta, observe 1. general behavior performance and death condition; 2. body weight, food utilization; 3. hematological indices; 4. blood parameters; 5. organ coefficient; 6. pathological examination.

1.4.3Ames test: by " health food inspection and assessment technical specification " version in 2003, adopt dressing plate incorporation methods, select Salmonella typhimurium saltant TA97, TA98, TA100, TA102 to test after qualified.

1.4.4 mouse marrow cell micro nuclear test: select 25-30gICR cleaning grade mice 50, tests after conforming 3 days.Be divided into 5 groups at random by body weight, often organize 10, male and female half and half.If 10,5, a 2.5ml/kg3 dosage group, negative control group (sterilized water, 20ml/kg gavage), positive controls (cyclophosphamide, 40mg/kg lumbar injection).Given the test agent sterilized water is prepared, and it is 50%, 25%, 12.5% that high, medium and low dosage contains given the test agent concentration respectively, with 20ml/kg gavage, adopts 30h to tested material method.Give given the test agent interval 24h twice, within 6 hours, animal is put to death after second time gives given the test agent, get the conventional film-making of breastbone, microscopy, every Mus counts 1000 Polychromatic erythrocyte (PCE), observation contains the polychromatic erythrocyte number of micronucleus and calculates microkernel incidence, in permillage, viewed mature erythrocyte number when every Mus counts 200 polychromatic erythrocytes, and calculate polychromatic erythrocyte and mature erythrocyte ratio (PCE/RBC).

1.4.5 mouse inbred strain: select body weight 25-30gICR cleaning grade mice 25, tests after conforming 3 days.Be divided into 5 groups at random by body weight, often organize 5.If 10,5, a 2.5ml/kg3 dosage group, negative control group (sterilized water, 20ml/kg gavage), positive controls (cyclophosphamide, 40mg/kg lumbar injection).Given the test agent sterilized water is prepared, and it is 50%, 25%, 12.5% that high, medium and low dosage contains given the test agent concentration respectively, with 20ml/kg gavage, and every day 1 time, continuous 5 days.Within the 35th day after giving given the test agent first, put to death animal, get the film-making routinely of both sides epididymal sperm filtrate, microscopy.Every Mus counts the sperm of 1000 structural integrities, calculates Sperm malformation rate (with percentage).

1.5 date processing: chmice acute Oral toxicity test data adopts SPSS10.0 software to carry out data statistic analysis; Rat 30 days feeding trials adopt SPSS16.0 software to carry out homogeneity test of variance to each test initial data; Micronucleus test result adopts Poisson distribution U inspection to carry out statistical disposition; Mouse inbred strain result adopts rank test to carry out statistical disposition.

2 results

2.1 acute toxicity test in mice

During experimental observation, normally, well-grown, has no any poisoning manifestations for each treated animal diet and activity, without dead.Chinese medicinal composition capsules of the present invention on the impact of Mouse Weight and death toll in table 15.Result shows that female, the male its mouse oral MTD of Chinese medicinal composition capsules of the present invention is greater than 22400mg/kg, and according to acute toxicity dose grading standard, this sample belongs to nontoxic level.

The impact of table 15 Chinese medicine composition Oral Liquid On Mice of the present invention acute oral toxicity

2.2 rat 30 days feeding trials

2.2.1 general behavior performance and death condition: Chinese medicine composition of the present invention gives rat 30 days with the dosage of 3.0ml/kg/d, 6.5ml/kg/d, 10.0ml/kg/d (being equivalent to 30 times of human body recommended dose, 65 times, 100 times), each treated animal generally shows and is showed no obvious abnormalities with behavior, without poisoning manifestations, without dead.

2.2.2 Chinese medicine composition of the present invention is on rat body weight, food utilization impact: Chinese medicine composition of the present invention gives rat 30 days with the dosage of 3.0mg/kg/d, 6.5mg/kg/d, 10.0mg/kg/d (being equivalent to 30 times of human body recommended dose, 65 times, 100 times), each dosage group rat the 30th day body weight, total foodstuff utilization rate compare with 0mg/kg/d group, there was no significant difference (P > 0.05).The results are shown in Table 16-table 19.

Table 16 Chinese medicine composition oral liquid of the present invention is on the impact of rat body weight

The impact that table 17 Chinese medicine composition oral liquid of the present invention increases weight on rat body weight

The food ration of rat respectively organized by table 18 Chinese medicine composition oral liquid of the present invention

Table 19 Chinese medicine composition oral liquid of the present invention is on the impact of rat chow utilization rate

2.2.3 Chinese medicine composition of the present invention is on the impact of rat blood index: per os gives rat Chinese medicine composition oral liquid of the present invention 30 days, measures the indexs such as each dosage group rat blood red blood cell count(RBC), hemoglobin level, numeration of leukocyte and classification thereof.From table 20-1 to table 20-2, each dosage group of indices compares with 0mg/kg/d group, the equal not statistically significant of difference (P > 0.05).

Table 20-1 Chinese medicine composition oral liquid of the present invention is on the impact of rat blood index

Table 20-2 Chinese medicine composition oral liquid of the present invention is on the impact of rat blood index

2.2.4 Chinese medicine composition of the present invention is on the impact of rat blood biochemical indicator: per os gives the Chinese medicine composition oral liquid of the present invention 30 days of rat various dose, measures the level of each dosage group rat blood serum glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, total protein, albumin, T-CHOL, triglyceride, blood urea nitrogen, creatinine and blood glucose.From table 21, female rats 3.0mg/kg/d group creatinine and male rat 6.5,10.0mg/kg/d group total protein are all higher than 0mg/kg/d group (P < 0.05), though above numerical value has significant difference, but numerical value is within this laboratory history normal range, and without dose-response relationship, do not think that there is bad biological significance.The every blood parameters of other each dosage groups compares with 0mg/kg/d group, the equal not statistically significant of difference (P > 0.05).

Table 21-1 Chinese medicine composition oral liquid of the present invention is on the impact of blood biochemistry of rats

Note: * and 0ml/kg/d compares, P < 0.05

Table 21-2 Chinese medicine composition oral liquid of the present invention is on the impact of blood biochemistry of rats

Note: * and 0mg/kg/d compares, P < 0.05

2.2.5 Chinese medicine composition of the present invention is on the impact of Rats Organs and Tissues absolute weight and relative weight: per os gives the Chinese medicine composition oral liquid of the present invention 30 days of rat various dose, measures each dosage group rat liver, kidney, spleen, testis, ovary absolute weight and relative weight (dirty/body).From table 22, the indices of each dosage group of Mus female, great and mighty or powerful compares with 0mg/kg/d group, the equal not statistically significant of difference (P > 0.05).

Table 22-1 Chinese medicine composition oral liquid of the present invention respectively organizes Rats Organs and Tissues absolute weight and relative weight

Table 22-2 Chinese medicine composition oral liquid of the present invention respectively organizes Rats Organs and Tissues absolute weight and relative weight

2.2.6 pathological examination

Each group of rat gross anatomy is showed no abnormal change.Microscopy result is as follows:

0mg/kg/d group female rats is totally 10 examples:

1. liver: lobules of liver clear in structure, liver rope marshalling; Hepatocyte size is basically identical, and nucleus size is homogeneous, and nuclear membrane, kernel are clear, Cytoplasm even dyeing, blood stasis 1 example that sinus hepaticus is slight.

2. kidney: kidney skin, medullary substance boundary clear, nephron structure is normal, and glomerule is without changes such as inflammatory change, fibrosis, hyaloid pathological changes, and renal tubules also has no obvious pathological changes,

3. spleen: red, white pulp is clear, central artery occupies acini lienalis central authorities, and corpusculum is without obvious atrophy, and snius lienis is expanded, and spleen trabeculae is normal.

4. Stomach duodenum: show that mucosa is normal, changes and rotten to the corn, ulcer without inflammatory.

5. ovary: the corpus luteum formed after the follicle of visible different developmental phases and ovulation in ovary or lean type.

0mg/kg/d group male rat is totally 10 examples:

1. liver: lobules of liver clear in structure, liver rope marshalling; Hepatocyte size is basically identical, and nucleus size is homogeneous, and nuclear membrane, kernel are clear, Cytoplasm even dyeing, slight hepatic cell steatosis 3 example.

4. Stomach duodenum: show that mucosa is normal, changes and rotten to the corn, ulcer without inflammatory.Under mucosa, muscle layer, placenta percreta all change without inflammatory.

5. testis: convoluted tubule of testis is made up of sustenticular cell and epithelial cell, elementary, secondary spermatocyte, and germ cell development is normal.

10mg/kg/d group female rats is totally 10 examples:

1. liver: lobules of liver clear in structure, liver rope marshalling; Hepatocyte size is basically identical, and nucleus size is homogeneous, and nuclear membrane, kernel are clear, Cytoplasm even dyeing, slight hepatic cell steatosis 1 example.

2. kidney: kidney skin, medullary substance boundary line are clear, nephron structure is normal, and glomerule is without changes such as inflammatory change, fibrosis, hyaloid pathological changes, and renal tubules also has no obvious pathological changes,

10mg/kg/d group male rat is totally 10 examples:

1. liver: lobules of liver clear in structure, liver rope marshalling; Hepatocyte size is basically identical, and nucleus size is homogeneous, and nuclear membrane, kernel are clear, Cytoplasm even dyeing, slight hepatic cell steatosis 2 example.

To sum up, have no liver,kidney,spleen that Chinese medicine composition of the present invention causes, Stomach duodenum, testis, ovary internal organs toxic pathology change.

2.3Ames tests: from table 23, table 24, and each dosage group of Chinese medicine composition of the present invention is returned change clump count and all do not exceeded 2 times that negative control group returns change clump count, also without dose-response relationship.And Chinese medicine composition of the present invention is to Salmonella typhimurium TA97, TA98, TA100, TA102 tetra-strain test strain, adding with when not adding S-9, being showed no and having caused gene mutation effect.

Table 23 Chinese medicine composition oral liquid of the present invention Salmonella reversion test returns change clump count (for the first time)

Table 24 Chinese medicine composition oral liquid of the present invention Salmonella reversion test returns change clump count (for the second time)

2.4 mouse marrow cell micro nuclear tests: from table 25, each dosage group micronuclear rates there was no significant difference (P > 0.05) compared with negative control group of Chinese medicine composition oral liquid of the present invention, positive controls is then significantly higher than negative control group (P < 0.01).Have no Chinese medicine composition Oral Liquid On Mice Micronucleus of the present invention formed and PCE/RBC ratio have an impact.

The impact of table 25 Chinese medicine composition Oral Liquid On Mice of the present invention bone marrow cell micronucleus incidence rate and polychromatic erythrocyte and mature erythrocyte ratio (PCE/RBC)

Note: compare with negative control group, P < 0.01

2.5 mouse inbred strain: from table 26, table 27, each dosage group rate of teratosperm compares with negative control group, there was no significant difference (P > 0.05), and positive controls mouse sperm deformity rate compares with negative control group and has significant difference (P < 0.01).Visible Chinese medicine composition Oral Liquid On Mice rate of teratosperm of the present invention does not have an impact.

The impact of table 26 Chinese medicine composition Oral Liquid On Mice of the present invention rate of teratosperm

Note: compare with negative control group, P < 0.01

The impact of table 27 Chinese medicine composition Oral Liquid On Mice of the present invention sperm deformity type and ratio

Effect example 4

Chinese medicine composition improving water flood human feeding trial of the present invention

1 test method: adopt two kinds of control design between self and group, select the patient suffering from insomnia for a long time that 120 examples are simple, at 18 ~ 60 years old age, be divided into test-meal group and matched group at random according to symptom weight, often organize 60 examples, test-meal group male 26 example, women 34 example, the mean age is 52.75 ± 10.25 years old, matched group male 29 example, women 31 example, the mean age is 51.26 ± 9.79.Test-meal group: take the Chinese medicinal composition granules that the embodiment of the present invention 2 prepares, matched group eats placebo, placebo outward appearance, color and luster, weight, instructions of taking are identical with the present invention.Experimenter takes 3 times everyone every day, and each 1 bag (5g/ bag), uses warm water delivery service.Duration of test normal diet, does not change original dietary habit, and the medicine of other treatment insomnia of stopping using and Chinese medicine composition, viewing duration is 90 days.

Symptom integral is observed: by the weight situation scores accumulated (serious symptom 3 points, moderate 2 points, slight 1 point) of insomnia.Two groups of symptom integral there was no significant difference (P > 0.05) before the treatment.Before test-meal, two groups of blood, urine, feces routine and hepatic and renal function, Chest X-rays, electrocardiogram, B ultrasonic etc. check all in normal range.

2 results

Self compare before and after the test-meal of test-meal group and compare between matched group group, clinical symptoms integration obviously reduces (P < 0.01), test-meal group crowd sleep quality obviously improves, and does not report other side effect, and Chinese medicine composition of the present invention is improved the function of sleep.The results are shown in Table 28.

Clinical symptoms integration before and after table 28 test-meal

* compares with before test-meal, P < 0.01; ^##compare between group, P < 0.01.

Effect example 5

Chinese medicine composition enhancing immunity human feeding trial of the present invention

1 test method: select the immunocompromised patients that 120 examples are simple, be divided into test-meal group and matched group at random by subject immune's power situation, often organize 60 examples, consider that the principal element affecting result is as age, sex, diet etc. as far as possible, carry out harmony inspection, to ensure the comparability between group.Test-meal group male 32 example, women 28 example, 48.72 ± 10.01 years old mean age; Matched group male 27 example, women 33 example, 47.45 ± 9.87 years old mean age.Test-meal group: take the embodiment of the present invention 4 gained Chinese medicine composition tablet, matched group eats placebo, and placebo outward appearance, color and luster, weight, instructions of taking are identical with the present invention.Experimenter takes 3 times everyone every day, each 2, uses warm water delivery service.Duration of test normal diet, does not change original dietary habit, takes 90 days continuously.

Before test-meal, two groups of blood, urine, feces routine and hepatic and renal function, Chest X-rays, electrocardiogram, B ultrasonic etc. check all in normal range, the equal no significant difference of content (P > 0.05) of two groups of experimenter's lymphocytes and macrophage, has comparability.

2 results

Take latter 90 days, before and after the test-meal of test-meal group, the content of lymphocyte and macrophage obviously increases (P < 0.01), apparently higher than matched group, compare between two groups and have significant difference (P < 0.01).Result shows, examination took Chinese medicine composition of the present invention after 90 days, self compare before and after the test-meal of test-meal group and compare between test-meal group with matched group group after test-meal, the content of lymphocyte and macrophage obviously increases (P < 0.01), illustrates that this invention has the function of enhancing human body immunity power.The results are shown in Table 29-table 30.

Blood lymphocytes change before and after table 29 test-meal

Blood macrophage change before and after table 30 test-meal

The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims

1. have a Chinese medicine composition for improving water flood, enhancing immunity effect, it is characterized in that, it comprises the raw material of following parts by weight:

2. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

3. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

4. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

5. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

6. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

7. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

8. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

9. the Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 1, it is characterized in that, it comprises the raw material of following parts by weight:

10. one kind has the pharmaceutical preparation of improving water flood, enhancing immunity effect, it is characterized in that, the extract of the Chinese medicine composition described in any one of claim 1 ~ 9 and pharmaceutically acceptable carrier are prepared into oral liquid, granule, capsule, tablet or pill.

The preparation method of Chinese medicine composition with improving water flood, enhancing immunity effect described in 11. any one of claim 1 ~ 9, is characterized in that, comprise the following steps:

A, by the parts by weight described in any one of claim 1 ~ 9, get Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add ethanol, heating and refluxing extraction, obtain ethanol extract;

B, get steps A ethanol extraction after medicinal residues and the Semen Ziziphi Spinosae of parts by weight described in any one of claim 1 ~ 9, Rhizoma Polygonati, Poria add water, heating extraction, obtain aqueous extract;

12. preparation methoies of Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 11, is characterized in that, comprise the following steps:

A, by the parts by weight described in any one of claim 1 ~ 9, get Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 10 ~ 90% ethanol of the volume of medical material weight 1 ~ 10 times amount, heating and refluxing extraction 1 ~ 3 time, each 1 ~ 3 hour, merge to obtain alcohol extract;

B, get Semen Ziziphi Spinosae, Rhizoma Polygonati, the Poria of the medicinal residues after steps A ethanol extraction and the parts by weight described in any one of claim 1 ~ 9, add the water of 1 ~ 15 medical material times amount, heating extraction 1 ~ 3 time, each 1 ~ 3 hour, merge to obtain aqueous extract;

C, steps A alcohol extract to be concentrated into medical material equivalent be that 0.8:1 ~ 2:1, step B Aqueous extracts is concentrated into medical material equivalent and is about 0.8:1 ~ 2:1, and mixing, continues to be concentrated into medical material equivalent and be about 1:1 ~ 2:1

13. preparation methoies of Chinese medicine composition with improving water flood, enhancing immunity effect according to claim 12, is characterized in that, comprise the following steps:

By the parts by weight described in any one of claim 1 ~ 9 in steps A, get Radix Panacis Quinquefolii, Radix Et Caulis Acanthopanacis Senticosi, Fructus Psoraleae, add 50% ethanol of medical material weight 5 times of volumes, heating and refluxing extraction 2 times, each 2 hours, merge to obtain alcohol extract;

Get the Semen Ziziphi Spinosae of parts by weight described in steps A ethanol extraction medicinal residues and any one of claim 1 ~ 9, Rhizoma Polygonati and Poria in step B, add the water of total medical material 10 times of volumes, heating decocts extraction 2 times, each 2 hours, merges to obtain aqueous extract;

In step C, steps A alcohol extract being concentrated into medical material equivalent is that 1:1, step B Aqueous extracts is concentrated into medical material equivalent and is about 1:1, after mixing, continues to be concentrated into medical material equivalent and is about 1.5:1.

Described in 14. claim 1 ~ 10 any one have improving water flood, enhancing immunity effect Chinese medicine composition preparation have improving water flood, enhancing immunity effect medicine or/and application in health product.