CN101816747A - Medicinal preparation for preventing and treating mental diseases such as insomnia and the like and preparation method thereof - Google Patents

Abstract

The invention provides a medicinal preparation for preventing and treating mental diseases such as insomnia and the like and a preparation method thereof. The medicinal preparation is mainly prepared from camellia branch, thin-leaf milkwort root-bark, dwarf lilyturf tuber and tuber fleeceflower stem serving as raw medicaments, or is compatible with partial or total medicinal materials comprising valeriana root, hawthorn fruit and aleppo avens. Compared with the prior art, the formula provided by the invention can be prepared into an oral preparation by a conventional preparation process; and the preparation has the effects of tranquilizing by nourishing the heart, nourishing yin and tonifying spleen, has good curative effect on symptoms such as insomnia, melancholy, amnesia and the like caused by heart-kidney imbalance and spleen-stomach yin deficiency, is safe to use, has no toxic or side effect, does not produce medicament resistance, has no influence on driving, high-altitude work and the like, and is a safe, effective and quality-controllable new Chinese medicament for preventing and treating the mental diseases such as the insomnia and the like.

Description

A kind of pharmaceutical preparation that prevents and treats mental sickness such as insomnia and preparation method thereof

Technical field

The present invention relates to a kind of pharmaceutical preparation that prevents and treats mental sickness such as insomnia and preparation method thereof, belong to technical field of Chinese medicines.

Background technology

Sleeping problems such as insomnia have become the ubiquitous serious public health problem in countries in the world.World Health Organization (WHO) was once investigated in 14 countries, and about 27% people has sleeping problems.The investigation of U.S.'s sleep foundation shows that about 50% American can have several days time at least a insomnia's symptom to occur weekly.In Europe, nearly 4%～22% people is subjected to having a strong impact on of insomnia, and the present insomnia's of China sickness rate is also up to 10%～20%.China Chinese Medical Association psychosis association once in Shanghai, ground such as Beijing, Guangzhou, Beijing, Hangzhou and Shandong have carried out the sleeping problems investigation that once has people more than 10,000 to participate in.Among the surveyee, exist easily wake up, wake up too early, length of one's sleep deficiency, sleep quality sleeping problems such as bad up to 42.5%.Insomnia becomes for a very general problem in China, and is particularly in the majority with women and old man.

Depression is called as " blue secret worry " in the west, show that according to relevant investigation the depression sickness rate is about 3%-5% in China, has had 2,600 ten thousand people of surpassing to suffer from depression at present.Along with the development of society, live in metropolitan white collars such as Beijing, Shanghai and Guangzhou and under the environment of the high competition of high pressure, become sick for this reason group of people at high risk rapidly.With high incidence forms distinct contrast be regrettably, at present the national prefectural level with the discrimination to depression of going to the hospital less than 20%.In existing patients with depression, only accepted relevant Drug therapy less than 10% people.World Health Organization's latest survey statistical analysis, the incidence rate of global depression is about 3.1%, and about developed country is near 6%, existing more than 8,900 ten thousand people of global serious symptom depressive illness patient in 2002, and the patients with depression in the whole world has reached 3.4 hundred million.In 20 years old adult population, patients with depression just increases with the speed in every year 11.3%.Expect 2005, the depression sickness rate will rise to 8～10% in developed country; The function residue will rise to the 2nd of the total class of disease due to being easy to the year two thousand twenty principal characteristic, be only second to ischemic heart desease.Depression also allows of no optimist in the situation of China, and depression is approximately 4% at the sickness rate of China at present.Show that according to using new some areas Epidemiological study data that classification of diseases and diagnostic system carried out China's depression prevalence is about about 10 ‰～15 ‰, close with developed country statistical result.Neuropsychiatric disease ranks first in the total burden of China's disease, accounts for 20% of the total burden of disease.Calculate that according to World Health Organization (WHO) Chinese neuropsychiatric disease is born the year two thousand twenty will rise to 1/4 of the total burden of disease.Have data to show that the people of China 70% is in sub-health state, the disease patient relevant with psychological stress accounts for crowd's 5%～10%, and somatopsychic illness, mental maladjustment have become frequently-occurring disease, commonly encountered diseases.China key cities typical hospital nervous system medication amount of money had reached about 14.20 hundred million yuan in 2002, and Beijing,Shanghai and Guangzhou three metropolitan proportions account for 63.28%, and antidepressants account for 1/5.

The pathogenic factor of amnesia is various, and its most important reason is the age, the nearest amnesia sickness rate trend that becomes younger, but youngster relatively, the easier trouble amnesia of the person in middle and old age more than 40 years old.Before and after people's best memory appeared at 20 years old, the function of brain began fall off then, and memory begins formal decline before and after 25 years old, and the age, big more memory was low more.Therefore the people of two teens and three teens is perplexed the thing that neither wonder by amnesia.In addition, amnesia also have its external cause, it is tired that lasting pressure and anxiety can make brain cell produce, and amnesia is worsened.Excessively smoking, drink, be deficient in vitamin etc. can cause that temporary memory worsens.Recently, the expert begins also to notice that psychological factor also has the influence that can not be ignored to the formation of amnesia, and the amesiac who goes to see a doctor has much symptoms of depression.In case the people is absorbed in depression, it is own and unconcerned to people in the society and thing only to pay close attention to depression doggedly, so the energy of brain is low, and brings out amnesia.According to statistics, the women has accounted for 60% among the amesiac, and the housewife has the amnesia experience more than 80%.

Insomnia is one of common clinical card, though do not belong to critical illness, often hinders people orthobiosis, work, study and health, and can increase the weight of or bring out diseases such as cardiopalmus, the thoracic obstruction, dizzy, headache, apoplexy.Obstinate insomnia brings secular misery to patient, even forms the dependence to the medicine of sleeping peacefully, and can cause iatrogenic disease and take the medicine of sleeping peacefully for a long time.Chinese medicine often can obviously improve sleep state, and not cause drug dependence and iatrogenic illness by adjusting the function of viscera negative and positive of qi and blood, thereby rather well received.Up to the present, mental sickness such as insomnia still do not have safe and effective medicine, calm clinically class medicine, this quasi drugs is relief of symptoms rapidly, but also cure the symptoms, not the disease, this quasi drugs toxic and side effects is bigger simultaneously, takes for a long time, human body is caused drug dependence and iatrogenic illness, and using such medicine can increase the danger that motor vehicle accident, death, fracture, mortality poisoning, physiological function decline and cognitive impairment take place.In order to develop the Chinese medicine that can safely, effectively prevent the treatment goat, the applicant has carried out a large amount of explorations and research.

Summary of the invention

Technical problem to be solved by this invention provides pharmaceutical preparation of mental sickness such as a kind of energy safety, effective control insomnia and preparation method thereof, medicine effect of the present invention is fast, have no side effect, and is a kind of new Chinese medicine of safe, effective, quality controllable mental sickness such as control insomnia.

In order to solve the problems of the technologies described above, the present invention adopts following technical scheme: the control insomnia waits the medicine of mental sickness, mainly is to be made by the following raw materials by weight percent medicine: Semen Pittospori Glabrati tea 10%～45%, Radix Polygalae 15%～20%, Radix Ophiopogonis 15%～30%, Caulis Polygoni Multiflori 25%～40%.

The medicine of mental sickness such as above-mentioned control insomnia, the consumption of each crude drug is preferably: Semen Pittospori Glabrati tea 26.7%, Radix Polygalae 17.8%, Radix Ophiopogonis 22.2%, Caulis Polygoni Multiflori 33.3%.

The preparation method of the medicine of mental sickness such as above-mentioned control insomnia is: get Semen Pittospori Glabrati tea, Radix Polygalae, Radix Ophiopogonis, Caulis Polygoni Multiflori four Chinese medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～3 time, the each decoction 1～3 hour, filter, it is 1.20～1.40 extractum that filtrate is concentrated into 60 ℃ of relative densities, and preparation process is made different pharmaceutical preparation routinely then.

The medicine of mental sickness such as aforementioned control insomnia, in order to reach better therapeutic effect, can also add Rhizoma valerianae latifoliae, Fructus Crataegi, Radix seu Herba Gei aleppici three flavor raw medicinal materials, the part by weight of each crude drug is: Semen Pittospori Glabrati tea 5%～40%, Radix Polygalae 5%～13%, Radix Ophiopogonis 10%～15%, Caulis Polygoni Multiflori 15%～22%, Rhizoma valerianae latifoliae 10%～15%, Fructus Crataegi 10%～15%, Radix seu Herba Gei aleppici 10%～15%.

The medicine of mental sickness such as above-mentioned control insomnia, the consumption of each component is preferably: Semen Pittospori Glabrati tea 16%, Radix Polygalae 10.7%, Radix Ophiopogonis 13.3%, Caulis Polygoni Multiflori 20%, Rhizoma valerianae latifoliae 13.3%, Fructus Crataegi 13.3%, Radix seu Herba Gei aleppici 13.3%.

The preparation method of the medicine of mental sickness such as above-mentioned control insomnia is: get Semen Pittospori Glabrati tea, Radix Polygalae, Radix Ophiopogonis, Caulis Polygoni Multiflori, Rhizoma valerianae latifoliae, Fructus Crataegi, Radix seu Herba Gei aleppici seven flavor medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～3 time, the each decoction 1～3 hour, filter, it is 1.20～1.40 extractum that filtrate is concentrated into 60 ℃ of relative densities, and preparation process is made different pharmaceutical preparation routinely then.

Medicine of the present invention can be prepared into oral formulations, comprises decoction, granule, oral liquid, syrup, soft extract, pill, tablet, hard capsule or soft capsule etc.

We are according to theory of Chinese medical science, utilize mental sickness such as interior application treatment insomnia, in line with the basic principle of " heresy is arranged and the person's of being insomnia eliminating the pathogen and refreshing from peace ", thereby the method for treatment is worked as head and is got mind tranquilizing and the heart calming, void person is aided with the method for nourishing the blood and yin QI invigorating, and real person controls the method with the eliminating phlegm heat clearing and blood circulation promoting.Control from specimen deficiency and excess opinion, Cure for insomnia, determined curative effect, effect is obviously.

Prescription medicine characteristic of the present invention: Rhizoma valerianae latifoliae: hot, little hardship, temperature.Promoting digestion and invigorating the stomach, regulating QI to relieve pain, the detoxifcation of dispeling the wind.The abdominal distention for the treatment of for stomachache, dyspepsia, infantile malnutrition, gastroenteritis, dysentery, rheumatalgia, soreness of the waist and knees.Semen Pittospori Glabrati tea: property is cold, bitter in the mouth, peppery.Go into hot warp.Heat clearing away, wind-damp dispelling is calmed the nerves; Jaundice, rheumatalgia, insomnia.Radix Polygalae: bitter, hot, tepor.GUIXIN, kidney, lung meridian.The Fructus Alpiniae Oxyphyllae of calming the nerves is eliminated the phlegm, detumescence.Be used for the insomnia and dreamful sleep that disarmony between the heart and kidney causes, forgetful palpitation with fear, staring spells, expectoration is not well, sore swollen toxin, breast swell and pain.Fructus Crataegi: sour in the mouth, sweet, slightly warm in nature.Appetite-stimulating indigestion-relieving, change stagnant removing food stagnancy, promoting blood circulation to remove blood stasis, the circulation of qi promoting of reducing phlegm.Be used for carnivorous stagnate long-pending, lump in the abdomen, abdominal distention feeling of fullness, the stasis of blood resistance stomachache, phlegm retention, have loose bowels, discharging fresh blood stool etc.Radix Ophiopogonis: sweet, little hardship is slightly cold.GUIXIN, lung, stomach warp.YIN nourishing and the production of body fluid promoting, lung moistening clears away heart-fire.Be used for dryness of the lung dry cough, the chronic consumptive disease cough, Tianjin wound is thirsty, vexed insomnia, interior-heat is quenched one's thirst, dryness of the intestine constipation, pharyngeal diphtheria.Caulis Polygoni Multiflori: property is flat, sweet in the mouth.Go into the heart, spleen, liver, kidney channel.Nourish heart, calm the nerves, collateral dredging dispels the wind, and controls the insomnia, impairment caused by overstrain, hyperhidrosis, blood deficiency general pain, carbuncle, scrofula, wind skin ulcer scabies.Radix seu Herba Gei aleppici: hot, bitter, flat.Analgesia, blood pressure lowering, regulating menstruation, expelling wind and removing dampness.Be used for hypertension, dizziness headache, menoxenia, lower abdominal pain, leucorrhea, infantile convulsion, lumbago, skelalgia of rheumatism; Carbuncle furuncle and phyma poison, traumatic injury are controlled in external.

Prescription side of the present invention separates: insomnia is with the deficiency length of one's sleep, Depth of sleep not enough and can not allaying tiredness, regain one's strength and energy is main syndrome feature.Wherein the length of one's sleep, deficiency person can show as difficulty falling asleep, slept night and easily woke up, and was difficult to sleep severe patient even all night be insomnia after waking up again.Sleep when waking up when the not enough person of Depth of sleep often shows as night, it is then disintoxicated to sleep, or the dream of sleeping night is many.Because the length of one's sleep and degree of depth quality is not enough, causing can not allaying tiredness after waking up, and shows as dizziness, headache, spiritlessness and weakness, cardiopalmus, forgetful, even malaise etc.Because individual variation, also inequality to the requirement of the length of one's sleep and quality, so the clinical judgment insomnia not only will be according to the time and the quality of sleeping, the more important thing is with can allaying tiredness, regain one's strength and energy is foundation.At reinforce insufficiency and reduce excessiveness, be aided with the base therapy method that tranquilizing the mind is a primary disease on the basis of adjustment internal organs negative and positive of qi and blood.The suitable reducing for the excess syndrome of excess syndrome, as dispersing the stagnated live-QI to relieve the stagnation of QI, pathogenic fire reducing clearing away phlegm, promoting digestion and regulating the middle JIAO.The suitable tonifying for deficiency syndrome of deficiency syndrome, as benefiting QI and nourishing blood, spleen invigorating, tonifying liver, kidney tonifying.Excess syndrome with the passing of time, QI and blood consumption is hindered, and also can transfer deficiency syndrome to, simulataneous insufficiency and excessive person controls suitable reinforcement and elimination in combination.The use of tranquilizing the mind method will be selected concrete method of treatment such as nourishing blood to tranquillize the mind, tranquillizing the mind by relieving convulsion, clearing away heart-fire for tranquillization respectively for use in conjunction with clinical, and notes cooperating spiritual healing, to eliminate nervous anxiety, keeps spirit happy.We cure mainly disarmony between the heart and kidney institute induced insomnia, melancholy, card such as forgetful, based on Semen Pittospori Glabrati tea, Radix Polygalae, focus on the Fructus Alpiniae Oxyphyllae of calming the nerves in the side; With YIN nourishing and the production of body fluid promoting Radix Ophiopogonis, lung moistening clears away heart-fire; Caulis Polygoni Multiflori nourishes heart, and calms the nerves, and two medicines are with the power of principal drug assistance tranquilizing by nourishing the heart; With Radix seu Herba Gei aleppici analgesia blood pressure lowering; With Rhizoma valerianae latifoliae, Fructus Crataegi two flavor strengthening the spleen and stomaches, regulate the flow of vital energy; All medicines share, and adopt heart and tranquilizing mind altogether, and the merit of YIN nourishing spleen invigorating can make that vexed insomnia difficulty is slept, melancholy, forgetful all diseases must be controlled.

Function of the present invention cures mainly: medicine of the present invention has tranquilizing by nourishing the heart, YIN nourishing spleen invigorating effect.Be used for insomnia that disarmony between the heart and kidney, deficiency of YIN of the spleen and stomach cause, melancholy, card such as forgetful.And safe in utilization, have no side effect, do not produce drug resistance, driving, work high above the ground etc. there are not influence, be a kind of new Chinese medicine of safe, effective, quality controllable mental sickness such as anti-treatment insomnia.

In order to verify that medicine of the present invention has excellent curative, the applicant has carried out series of experimental research, and is specific as follows:

One, clinical practice

1, physical data: clinical patient's 120 examples of accepting for medical treatment altogether, male's 52 examples, women's 68 examples, older person 65 years old, reckling 23 years old, the elder of the course of disease 6 years, the shortest person 15 days.This is clinical to be divided into treatment at random and to organize 80 examples, matched group 40 examples, two groups of no significant differences.

2, Therapeutic Method

2.1 treatment group: execute and control, syndrome by " disease of tcm diagnosis criterion of therapeutical effect ": disarmony between the heart and kidney institute induced insomnia, melancholy, forgetful etc. seen diseases such as dizziness, headache, spiritlessness and weakness, cardiopalmus, forgetful, even malaise.Control with yin nourishing and clear away heart-fire the Fructus Alpiniae Oxyphyllae of calming the nerves.Method of administration: Semen Pittospori Glabrati tea 12g, Radix Polygalae 8g, Radix Ophiopogonis 10g, Caulis Polygoni Multiflori 15g, Rhizoma valerianae latifoliae 10g, Fructus Crataegi 10g, Radix seu Herba Gei aleppici 10g.It is for oral administration to fry in shallow oil soup, one day 1 dose, 30 days is a course of treatment.

2.2 matched group: use NAOLEJING KELI, nourish heart, brain-strengthening, mind-easing function.Be used for depressed, easily frightened insomnia, agitation and children's's night restlessness are slept.Warm boiled water, a 14～42g, 3 times on the one.

3, observation of curative effect

3.1 observation item: whole patients all do routine blood test, routine urinalysis, blood urea nitrogen, blood pressure detection before and after the treatment.

3.2 criterion of therapeutical effect: effectively: the primary symptom insomnia all disappears, and other transference cures, lab testing recover normal; Produce effects: primary symptom insomnia and other sxs, lab testing has improvement; Invalid: primary symptom insomnia and other symptom lab testing no changes.

3.3 result: 80 examples are organized in treatment, effective 36 examples, and produce effects 38 examples, invalid 6 examples, total effective rate is 92.5%; Matched group 40 examples, effective 14 examples, produce effects 20 examples, invalid 6 examples, total effective rate is 85%.Treatment group curative effect is apparently higher than matched group.

The clinical total effects of table 1

4, discuss: psychotic disorders such as insomnia are the internal medicine refractory disease, and the Western medicine curative effect is satisfied inadequately, and side effect is big.Chinese medicine is at psychotic disorder satisfactory effects such as Cure for insomnias, and this side has effects such as tranquilizing by nourishing the heart, YIN nourishing spleen invigorating, and insomnia, card such as melancholy, forgetful are had good curative effect, worth clinical application.

Two, preliminary drug effect and prescription contrast test

1, experiment material

1.1 laboratory animal: Kunming mouse, cleaning level, body weight 18-22g.

1.2 medicine and reagent: be subjected to reagent: preparation extract of the present invention No. 1 and No. 2, Kweiyang spring section's Pharmaceutical research and development company limited provides specification: each 2 bag * 100g, clinical usage and consumption: 3 times on the one, inferior 1.2g/ (being equivalent to primary crude drug 10.5g), facing the time spent, to be made into suspension with distilled water standby.Contrast medicine: sedative jujube kernel capsule; Pentobarbital sodium.

1.3 experiment equipment: BS110S precise electronic balance (Beijing Sai Duolisi joint-stock company), SHA-C temperature controlled water bath oscillator (all over the country industrial corporation in Shenzhen), timer (the Kweiyang perseverance is because of biotech firm).

2, method and result are to the influence of pentobarbital sodium syngignoscism: white mice is divided into 8 groups at random, and No. 1, preparation extract of the present invention and No. 2 high, medium and low dosage groups, sedative jujube kernel capsule group and blank group are irritated stomach every day once, continuous 4 days.Respectively organized equal ip pentobarbital sodium 30mg after the last administration in l hour.Observe Mus number and dropping asleep latency that righting reflex loss in the mice 1 hour surpasses 1min, sleeper not in 1 hour, dropping asleep latency calculated by 60 minutes, calculate the sleeping rate and the length of one's sleep, the result shows that preparation extract of the present invention can obviously increase sleeping rate and the dropping asleep latency of white mice, prolongs the length of one's sleep.No. 1, preparation extract of the present invention and No. 2 comparisons, No. 2 the result is better than No. 1.

Table 2 pair pentobarbital sodium hypnotic synergism

The synergism of table 3 pair pentobarbital sodium sleep

Three, preparation process thereof research

1, preparation technology

1.1 prescription:Semen Pittospori Glabrati tea 12g, Radix Polygalae 8g, Radix Ophiopogonis 10g, Caulis Polygoni Multiflori 15g, Rhizoma valerianae latifoliae 10g, Fructus Crataegi 10g, Radix seu Herba Gei aleppici 10g.

1.2 preparation technology:Above seven flavor medicine material decocts with water twice, adds 10 times in water at every turn, decocts 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, vacuum drying is pulverized, and crosses 80 mesh sieves, add right amount of auxiliary materials, mixing is granulated, drying, granulate sieves, capsule is made in fill, promptly.

1.3 dosage form:The original formulation usage is taken for frying in shallow oil soup, and the preliminary test of pesticide effectiveness shows that also water is promoted sleeping rate and the dropping asleep latency that extractum obviously increases white mice, prolongs the length of one's sleep, and therefore, the consideration dosage form is an oral formulations.This experiment is carried out technical study with hard capsule.

1.4 technological process

2, Study on Preparation

2.1 process route is determined:This product prescription is made up of Semen Pittospori Glabrati tea, Radix Polygalae, Radix Ophiopogonis, Caulis Polygoni Multiflori, Rhizoma valerianae latifoliae, Fructus Crataegi, Radix seu Herba Gei aleppici 7 flavor medicines, takes to fry in shallow oil soup.The character of determining to take into full account each medical material in the prescription of process route.The character of each medical material is as follows in this project prescription: (1) Rhizoma valerianae latifoliae: this product suffering, little hardship, temperature.Has promoting digestion and invigorating the stomach, regulating QI to relieve pain, the detoxifcation of dispeling the wind.Be used to the abdominal distention of having a stomachache, dyspepsia, infantile malnutrition, soreness of the waist and knees.This product main component is a bornival; Also contain australene and contain alkaloids such as valerianine, chatinine, valerianae alkaloid A, valerianae alkaloid B, actinidine, valerianine.Have sedation, can strengthen corticocerebral process of inhibition, lower reflex excitability, remove smooth muscle spasm.(2) Semen Pittospori Glabrati tea: this product hardship, tepor.Has promoting blood circulation to remove obstruction in the collateral, synthetism detumescence, detoxifcation pain relieving.Be used for hypertension, neurasthenia, emission, cough, limbs fatigue, hematuria.(3) Radix Polygalae: this product hardship, suffering, tepor.Have the Fructus Alpiniae Oxyphyllae of calming the nerves, eliminate the phlegm, detumescence.Be used for the insomnia and dreamful sleep that disarmony between the heart and kidney causes, forgetful palpitation with fear, staring spells.This product main component is the bessisterol glucoside, bessisterol glucoside 6 '-the O cetylate, stigmasterol, (2-8Z) chemical constituent of three tetradecenoic acids has the effect of the Fructus Alpiniae Oxyphyllae of calming the nerves.(4) Fructus Crataegi: this product sour in the mouth, sweet, slightly warm in nature.Have appetite-stimulating indigestion-relieving, change stagnate removing food stagnancy, promoting blood circulation to remove blood stasis, the circulation of qi promoting of reducing phlegm.Be used for carnivorous stagnate long-pending, lump in the abdomen, abdominal distention feeling of fullness, the stasis of blood resistance stomachache, phlegm retention, have loose bowels, discharging fresh blood stool etc.The main component of Fructus Crataegi is a Flavonoid substances, mainly contains flavonoid glycoside, flavonol and the glycoside thereof, dioxygen flavonoid glycoside, the polymerization flavonoid that contain carbon bond.The composition of another kind of outbalance is a triterpene substance, heart tonifying is arranged, increase coronary blood flow, improves important function such as blood flow circulation.In addition, contain organic acid such as chlorogenic acid, caffeic acid and tannin, the acid anhydride of tanning, epicatechol, choline, acetylcholine, Sitosterolum, carotene and lot of V itC etc. in the Fructus Crataegi.Can prevent and treat cardiovascular disease, have blood vessel dilating, coronary blood flow increasing, improve the heart vigor, the stimulating central nervous system system, bring high blood pressure down and cholesterol, vessel softening and diuresis and sedation.(5) Radix Ophiopogonis: sweet, the little hardship of this product is slightly cold.Have YIN nourishing and the production of body fluid promoting, lung moistening clears away heart-fire.Be used for dryness of the lung dry cough, Tianjin wound is thirsty, vexed insomnia, and interior-heat is quenched one's thirst.Total Saponin, total amino acids low dose all have significant positive inotropic and increase the cardiac output effect in this product, and coronary flow is increased; And heavy dose of total Saponin, total amino acids and total sugar all produce inhibition to heart, and myocardial contraction is weakened, and cardiac output reduces.Total Saponin, total amino acids and total sugar do not have obvious influence to heart rate.Dual regulation and antibacterial action to blood glucose, immunologic function.(6) Caulis Polygoni Multiflori: the sweet little hardship of this product, flat.Have and nourish heart, calm the nerves, collateral dredging dispels the wind.Be used for the insomnia, impairment caused by overstrain, hyperhidrosis, blood deficiency general pain.Stem contains the anthraquinone class, is mainly emodin, chrysophanol or physcione, all exists with conjunction type.(7) Radix seu Herba Gei aleppici: this product suffering, hardship, flat.Has analgesia, blood pressure lowering, regulating menstruation, expelling wind and removing dampness.Be used for hypertension, dizziness headache, menoxenia, lower abdominal pain, leucorrhea, infantile convulsion, lumbago, skelalgia of rheumatism.This product contains chemical constituents such as gein, volatile oil, tannin, resin.For Guizhou Province's traditional herbal medicine commonly used, to market one's own products, output is bigger.Vigorate qi and replenish the blood is arranged, the tonifying YANG tonify deficiency, the function of yin nourishing strengthening the spleen and stomach so be the key medicine that treatment among the people is had a dizzy spell and tonify deficiency is weak, therefore is referred to as dizzy medicine again.

In sum, in conjunction with the character characteristics of each medical material in the prescription, water extraction is adopted in the decision of this preparation, now its experimental result is reported as follows.

2.2 decocting process research

(1) factor level is established: the factor that influence decocts mainly contains the following aspects: amount of water, decocting time, decoction number of times etc.Therefore we have carried out the quadrature investigation of 3 factors, 3 levels to these three principal elements, with preferred optimal processing parameter.The factor level table of orthogonal test sees Table 4:

Table 4 decocts orthogonal test factor level table

(2) index is selected: the multi-flavor medicine contains flavone compound among the we, modern study shows, chromocor compound is to cardiac-cerebral ischemia damage, hepatic injury, ARR protective effect and analgesia thereof, and therefore free radical resisting and antitumor etc. act on, its extracted amount as the orthogonal test evaluation index; The prescription Chinese crude drug also contains fat-soluble active ingredients such as alkaloid, and in order fully to reflect extraction effect, we measure the content of 60% ethanol soluble extraction in the extract, and also make the orthogonal test evaluation index with it; In addition, dried cream yield also is a conventional index of estimating extraction effect, and it directly influence the regulation of obeying dosage and single oral dose day, thus also with it as one of orthogonal test evaluation index.It is preferred that this test intended employing comprehensive grading method is carried out process conditions, because dried cream yield and effect amount are not proportional, stipulates that its balance is divided into 30 fens; The balance of 60% ethanol soluble extraction is divided into 30 fens; Effective ingredient in the total flavones side of being can directly reflect extraction effect, is 40 fens so stipulate the balance branch of this index.

(3) sample preparation: get 1 recipe quantity medical material, amount to 75g, carry out water by each orthogonal test condition of table 4 and carry, medicinal liquid concentrates and is settled to 100ml after filtering with 300 order filter clothes.Standby.

(4) dried cream yield is measured: precision is got the medicinal liquid 25ml after each orthogonal test concentrates, put respectively in the evaporating dish that has been dried to constant weight, and water bath method, residue takes out in 105 ℃ of dryings 3 hours, puts in the exsiccator and places 30 minutes, weighs, and calculates dried cream yield.

(5) 60% ethanol soluble extractions are measured: precision is got the medicinal liquid 50ml after each orthogonal test concentrates, adding ethanol respectively makes and contains alcohol amount and reach 60%, left standstill cold preservation 24 hours, filter, the filtrate water bath method, residue was in 105 ℃ of dryings 3 hours, take out, place exsiccator to place 30 minutes, weigh, calculate the extractum yield.

(6) total flavones is measured

The preparation of reference substance solution: precision takes by weighing 120 ℃ of control substance of Rutin that are dried to constant weight an amount of, puts in the 25ml measuring bottle, and it is an amount of to add methanol, puts that slight fever makes dissolving in the water-bath, puts coldly, adds methanol to scale, shakes up; Precision is measured 10ml, puts in the 100ml measuring bottle, adds water to scale, shakes up, and makes the solution that contains rutin 0.20192mg among every lml, promptly gets reference substance solution;

The standard curve preparation: precision is measured reference substance solution 1ml, 2ml, 3ml, 4ml, 5ml, 6ml, put respectively in the 25ml measuring bottle, respectively add water to 6.0ml, add 5% sodium nitrite solution 1ml, shake up, placed 6 minutes, add 10% aluminum nitrate solution 1ml, placed 6 minutes, hydro-oxidation sodium test solution 10ml adds water to scale again, shaking up, placed 15 minutes, is blank with the corresponding reagent; According to ultraviolet visible spectrophotometry, measure absorbance at 510nm wavelength place, be vertical coordinate with the absorbance, concentration is abscissa, the drawing standard curve;

The preparation of need testing solution: get this product under the content uniformity item, mixing, get 0.2g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 70% ethanol 25ml that adds, weigh, ultrasonic 10min places room temperature, supply with 70% ethanol and to subtract weight loss, filter, the accurate absorption in subsequent filtrate 1ml to the 25ml volumetric flask adds water to 5ml, method under the sighting target directrix curve preparation, make need testing solution from " adding water to 6.0ml " with the method operation, measure absorbance in accordance with the law, read the weight that contains anhydrous rutin the need testing solution from standard curve, calculate, promptly.Orthogonal experiments and interpretation of result see Table 5, table 6.

Table 5 decocts the orthogonal experiments table

Annotate: dried cream yield scoring=(dried cream yield/maximum dry cream yield) * 30

60% ethanol soluble extraction scoring=(extractum yield/maximum extractum yield) * 30

Total flavones extracted amount scoring=(extracted amount/maximum extracted amount) * 40

Comprehensive grading=dried cream yield scoring+60% ethanol soluble extraction scoring+total flavones amount of getting scoring

Table 6 decocts analysis of variance table

From table 5,6 analysis results as can be known, each factor effect primary and secondary is A＞B＞C; A, B, C factor all have significant difference, A in the A factor ₃＞A ₂＞A ₁So, select A ₃B in the B factor ₃＞B ₁＞B ₂So, select B ₃C in the C factor ₂＞C ₃＞C ₁So, select C ₂Therefore optimised process is A ₃B ₃C ₂Promptly add 10 times of water gagings, decocted 3 hours at every turn, decoct twice.

2.3 best decocting process checking:Because preferred optimised process is not included in 9 tests of orthogonal array, so it is verified.Get orthogonal test with a collection of medical material, press A ₃B ₃C ₂Experimentize, verify 3 batches altogether, checking the results are shown in Table 7:

Table 7 decocts optimised process checking result

The checking result shows that this technology extractum yield, 60% ethanol soluble extraction content and total flavones extracted amount are all more stable, can be used as the optimised process of extraction.

2.4 concentration technology is investigated:The method for concentration that workshop is commonly used has normal pressure to concentrate and concentrating under reduced pressure.Concentrating under reduced pressure have consuming time less, characteristics that thickening temperature is low, therefore heat-sensitive ingredients is destroyed lessly, along with improving constantly of pharmaceutical equipment manufacturing technology, present Chinese medicine workshop has been more, and to adopt concentrating under reduced pressure be main.For with produce actual combining closely, the concentrated mode of this product adopts the concentrating under reduced pressure method.

Get 2 times of recipe quantity medical materials, extract by best decocting process, the decoction liquor concentrating under reduced pressure (0.06～-0.08Mpa, 80 ℃) to thick extractum, recording at this moment, the extractum relative density is about 1.25(60 ℃), it is an amount of to get extractum, the same method is measured wherein general flavone content, and result of the test sees Table 8.

Determination of total flavonoids result in table 8 concentrated extract

Result of the test shows: adopt pressure reducing mode that this product extracting solution is concentrated, general flavone content is stable in the prescription, and illustration method is feasible.

2.5 drying process:Adopt normal pressure and drying under reduced pressure dual mode that drying process is investigated respectively, with the thick extractum mixing in the concentration technology investigation, be divided into 3 parts, carry out drying by condition in the table 9 respectively, gained extract powder content of total flavone, color and luster, drying time to serve as the investigation object, with this drying mode is carried out preferably the results are shown in Table 9.

The different drying mode investigation tables of table 9

Last watch test result shows that drying mode and drying condition do not have obvious influence to puerarin content, but constant pressure and dry extractum color and luster is dark, required time is long, and by contrast, adopting decompression is that the drying process parameter is more suitable for 70 ℃.

2.6 extract characteristic research

(1) character of extract powder: the pitchy powder of this product extract powder for behind drying under reduced pressure, being prepared into, in order to grasp the character of extract powder, be convenient to preparation research, we have measured the moisture absorption percentage rate and the flowability of extract powder.

(2) the moisture absorption percentage rate is measured: get proper amount of dry extractum, pulverize, cross 80 mesh sieves, put P2O5 exsiccator inner drying 48 hours, the glass exsiccator that simultaneously bottom is filled the NaCl supersaturated solution is put into 25 ℃ calorstat 24 hours, and its internal relative humidity (RH) is 75%.In the weighing botle of dry constant weight, add an amount of extract powder, the about 2mm of thickness, precision is weighed and is placed in the above-mentioned glass exsiccator, opens the weighing bottle cap; Regularly weighing is calculated as follows the moisture absorption percentage rate:

Table 10 extract powder moisture absorption percentage rate measurement result table

(3) measure angle of repose: adopt the fixed funnel method to measure extract powder (80 order) angle of repose: with 3 funnels series connection and be fixed in suitable height (3cm) on the graph paper of horizontal positioned, carefully extract powder is poured in the uppermost funnel along hopper walls, till the extract powder apex partis petrosae termination that forms on the graph paper contacts bottom bell mouth, measure the conical base diameter, be calculated as follows out a angle of repose:

Table 11 extract powder measurement result angle of repose

Extract powder moisture absorption percentage rate and angle of repose measurement result show that the extract powder moisture resistance is poor, mobile bad, be unsuitable for direct granulation, should add appropriate amount of auxiliary materials adjustment.

2.7 adjuvant screening

2.7.1 the supplementary product kind screening: the kind of adjuvant directly determines particulate hygroscopicity and flowability.Be commonly used to improve the granule hygroscopicity and lactose, starch and dextrin etc. arranged with mobile adjuvant.Get above-mentioned 3 kinds of adjuvants respectively by table 12 and add in the extract powder, mixing, with 75% ethanol system soft material, 10 orders are made granule excessively, and 65 ℃ of dry 15min are excessively behind the 10 mesh sieve granulate, again in 65 ℃ of dryings.Measure particulate moisture absorption percentage rate and angle of repose by preceding method.The results are shown in Table 12,13.

Table 12 different auxiliary material and extract powder compatibility table

Table 13 different auxiliary material makes particulate index inspection

Table 14 different auxiliary material proportioning makes particulate moisture absorption percentage rate

As seen from table, different auxiliary material is with after dried cream powder mixes in varing proportions, and 3 groups of sample hydroscopicities are 1＞3＞2 in proper order.The hydroscopicity minimum (60h) of No. 2 prescriptions (single use starch) wherein, good fluidity; No. 3 prescriptions (single dextrin of using) the little tide of granule.Take all factors into consideration and select prescription down No. 2.

2.7.2 supplementary product consumption screening: the consumption of adjuvant should satisfy under the prerequisite that preparation requires, and reduce consumption is principle as far as possible.Get starch respectively by table 15 and add in the extract powder, press preceding method and granulate back particulate moisture absorption percentage rate of mensuration and angle of repose.The results are shown in Table 15,16.

Table 15 supplementary product consumption compatibility table

The particulate moisture absorption percentage rate of table 16 different auxiliary material consumption

The different starch consumptions of table 17 particulate angle of reposes

Above-mentioned result of the test shows, it is many more to add the adjuvant amount, and particulate anti-wettability power and flowability are good more, and wherein every 20g extractum adding adjuvant 10g is suitable with adding 12g effect, in order to save production cost, we select every 20g extract powder to add adjuvant 10g is the supplementary product consumption parameter.

2.8 preparations shaping technical studyThe present invention is an extraction process by water, the gained extractum moisture absorption, it is more suitable to make granule, but adopts conventional the granulation to be difficult to realize, so use certain density alcohol granulation, concentration of alcohol is selected: get extract powder 20g, add starch 10g, mixing is used 60%, 75%, 95% alcohol granulation respectively, investigating granulates is difficult to degree and makes particulate quality, the results are shown in Table 18.

Table 18 different concentration ethanol granulation information slip

Experimental result shows, makes granular mass the best with 75% ethanol, and therefore, selecting 75% ethanol is this product granulation solvent.

2.9 the preparation prescription and the amount of making are determined:By the laws and regulations requirement that new drug is declared, the new drug prescription must be about 11% according to 3 batches of dried cream yields of pilot scale and calculate by 1000 preparation unit's statements, and this product preparation prescription calculates that process is as follows:

(1) dose of respectively distinguishing the flavor of in the preparation prescription: former prescription ratio is Semen Pittospori Glabrati tea 1.2, Radix Polygalae 0.8, Radix Ophiopogonis 1, Caulis Polygoni Multiflori 1.5, Rhizoma valerianae latifoliae 1, Fructus Crataegi 1, Radix seu Herba Gei aleppici 1, calculates in this ratio that each medical material amount is in this product preparation prescription: Semen Pittospori Glabrati tea 420g, Radix Polygalae 280g, Radix Ophiopogonis 350g, Caulis Polygoni Multiflori 525g, Rhizoma valerianae latifoliae 350g, Fructus Crataegi 350g, Radix seu Herba Gei aleppici 350g.Be that to contain the crude drug total amount be 2625g to preparation prescription.

(2) every capsules contains the crude drug total amount: every contains crude drug total amount=crude drug total amount ÷ preparation unit; That is: every contains crude drug total amount=2625g ÷ 1000=2.625g

(3) add the adjuvant amount in the preparation process

1. every prescription dry extract receipts amount: it is 2625g that preparation prescription contains the crude drug total amount, calculates if be about 10% according to dried cream yield, and then every prescription dry extract receipts amount is: every prescription dry extract receipts amount=prescription contains crude drug total amount * dried cream yield.That is: every prescription dry extract receipts amount=2625g * 11%=288.8g

2. supplementary product consumption is determined: by preceding test as can be known, the ratio of dry extract and adding starch is 20: 10 in this product preparation process, calculates the starch consumption thus and is: the every prescription starch consumption=dried cream receipts of every prescription amount * 10 ÷ 20.That is: starch consumption=288.8g * 10 ÷ 20=144.4g.It is dry extract receipts amount and starch consumption sum that every prescription makes the content amount, and by 1., 2. as can be known, this product makes content 433.2g.Consider that the medical material collecting season is different with the place of production, and the influence of production technology, dry extract receipts amount can slightly fluctuate, and we are described as supplementary product consumption: add right amount of auxiliary materials, making the content amount of making is 450g.

2.10 the finished product loading amount is determined:The finished product loading amount =The content amount of the making ÷ amount of making; That is: finished product loading amount =1000=0.45g/ of 450g ÷ grain.

2.11 pilot scale researchGet 10 times of recipe quantity medical materials, by work out to such an extent that process route carries out middle trial production, the production technology index is carried out comprehensive assessment, medical material and finished product are carried out performance rating, the results are shown in Table 19.

Table 19 pilot plant test result

The pilot plant test result of study shows that the every technical parameter of product of the present invention is stable, and feasible process is described, is fit to produce in batches.

2.12 the preparation technology of part dosage form of the present invention

(1) preparation technology of hard capsule: the weighting profit requires 2 or the prescription of claim 4, decocts with water twice, adds 10 times in water at every turn, decocts 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, vacuum drying is pulverized, and crosses 80 mesh sieves, add right amount of auxiliary materials, mixing is granulated, drying, granulate sieves, fill is made 1000, promptly.

(2) preparation technology of tablet: the weighting profit requires 2 or the prescription of claim 4, decocts with water twice, adds 10 times in water at every turn, the each decoction 3 hours filters merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, add right amount of auxiliary materials, mixing, granulate, drying adds the moderate lubrication agent, mixing, tabletting, bag film-coat, make 1000, promptly.

(3) preparation technology of soft capsule: the weighting profit requires 2 or the prescription of claim 4, decoct with water twice, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.15～1.20(60 ℃) extractum, add ethanol, make and contain alcohol amount and reach 60%, left standstill 24 hours, and got supernatant, filter, reclaiming ethanol and being concentrated into relative density is 1.25～1.30(60 ℃) extractum, vacuum drying is pulverized, and sieves, add right amount of auxiliary materials, grind well, be pressed into 1000, promptly.

(4) preparation technology of oral liquid: the weighting profit requires 2 or the prescription of claim 4, decocts with water twice, adds 10 times in water at every turn, the each decoction 3 hours filters merging filtrate, being evaporated to relative density is 1.15～1.20(60 ℃) extractum, add ethanol, make to contain the alcohol amount and reach 60%, left standstill 24 hours, and got supernatant, filter, filtrate recycling ethanol adds an amount of correctives to there not being the alcohol flavor, an amount of antiseptic, supply with boiled water, make 1000ml, promptly.

(5) preparation technology of granule: the weighting profit requires 2 or the prescription of claim 4, decocts with water twice, adds 10 times in water at every turn, the each decoction 3 hours, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, add right amount of auxiliary materials, mixing is granulated drying, make the 300g(Sugarless type), the 1000g(sugar-containing type), promptly.

Four, Pharmacodynamic test of active extract research

1, experiment material

1.1 medicine:Be subjected to reagent: preparation semi-finished product of the present invention (medicated powder), Kweiyang spring section's Pharmaceutical research and development company limited provides specification: the 8kg/ bag, clinical usage and consumption: 3 times on the one, 1.35g/ time, facing the time spent, to be made into suspension with distilled water standby; Positive control drug: sedative jujube kernel capsule, Guizhou Tongjitang Chinese Medicines C., clinical usage and consumption: 3 times on the one, 2.25g/ time, facing the time spent, to be made into suspension with distilled water standby; Pentobarbital sodium; Chlorpromazine HCL injection; Caffeine and sodium benzoate injection; Morphine.

1.2 animal:White mice, body weight 18-22g.The wistar rat, 180-220g.

1.3 instrument:The photoelectric counting instrument; WMZ-707l type temperature indicator.

2, method and result

2.1 influence to the white mice autonomic activitiesGet 50 of mices, be divided into 5 groups at random, 10 every group, blank group (distilled water), positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg), each organizes gastric infusion, every day 1 time, for three days on end, after the last administration 1 hour, measure each Mus 10min autonomic activities number of times (each 5rnin of left and right dish merges statistics) with the photoelectricity calculating instrument.The result shows and sees Table 20 that high, medium and low dosage group of the present invention and blank group relatively autonomic activities counting all obviously reduce (P＜0.01).

The influence of table 20 pair mice autonomic activities

2.2 influence to the pentobarbital sodium syngignoscismGet 50 of mices, be divided into 5 groups at random, grouping is irritated stomach every day once, continuous 4 days with 2.1.Respectively organized equal ip pentobarbital sodium 30mg after the last administration in l hour.Observe Mus number and dropping asleep latency that righting reflex loss in the mice 1 hour surpasses 1rain, sleeper not in 1 hour, dropping asleep latency calculated by 60 minutes, calculated the sleeping rate and the length of one's sleep, the results are shown in Table 21, table 22.

Table 21 pair pentobarbital sodium hypnotic synergism

The synergism of table 22 pair pentobarbital sodium sleep

The result shows that height of the present invention, middle dosage group can obviously increase sleeping rate and the dropping asleep latency of white mice, prolongs the length of one's sleep.

2.3 influence to the chlorpromazine syngignoscismGet 50 of mices, be divided into 5 groups at random, 10 every group, grouping is with 2.1, gastric infusion, every day 1 time, continuous 4 days, after the last administration 1 hour, each organizes ip chlorpromazine 12.8mg/kg, observes and respectively organizes the Mus number that righting reflex loss surpasses 1min in 1 hour, calculates dropping asleep latency and sleeping rate, last sleeper in 1 hour, calculated by 60 minutes incubation period.See Table 23.Show that preparation of the present invention can obviously improve sleeping rate, and the trend that prolongs dropping asleep latency is arranged.

Table 23 pair chlorpromazine hypnotic synergism

2.4 collaborative pentobarbital sodium suppresses the effect of caffeine and sodium benzoate central excitationWith 60 of mices, be divided into 6 groups at random: blank group, model control group, positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg).Equal gastric infusion, once a day, continuous 4 days.40min is except that the blank group before the last administration, all the other 5 groups equal sc caffeine and sodium benzoate 0.19g/kg, and 6 groups of equal ip pentobarbital sodium 37mg/kg survey dropping asleep latency, the length of one's sleep and sleeping rate then behind the last gastric infusion 40min.Not sleeping person presses 60min incubation period and calculates in 1 hour, and sleep surpasses 1 hour, presses 60min the length of one's sleep and calculates.The results are shown in Table 24.Model group and normal control group compare, and dropping asleep latency obviously prolongs and the shortening length of one's sleep, shows that caffeine and sodium benzoate has caused central excitation.Each group of preparation of the present invention significantly shortens with caffeine and sodium benzoate group comparison dropping asleep latency, and the length of one's sleep, significant prolongation showed that preparation of the present invention can suppress the central excitation effect of caffeine and sodium benzoate.

Table 24 pair collaborative pentobarbital sodium suppresses the central excitation effect of caffeine and sodium benzoate

2.5 analgesic activity

(1) hot plate method: get 60 of mices, be divided into 6 groups at random, every group 10, blank group, model control group, positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg).Gastric infusion, every day 1 time, for three days on end, after the last medication 1 hour, aluminum matter hot plate placed in 55 ℃ ± 0.5 ℃ the water-bath, licking metapedes for the 1st time with mice is that index is surveyed the threshold of pain, positive controls subcutaneous injection morphine 25mg/kg, survey the threshold of pain behind the 30min, the results are shown in Table 25, show that preparation of the present invention has significant analgesia role.

The analgesic activity (hot plate method) of table 25 pair mice

(2) writhing method: get 60 of mices, grouping and medication are with (1), and the last administration was given white mice ip1% acetic acid 0.2ml/10g respectively in 1 hour, observe to turn round the body number of times in the 10min, the results are shown in Table 26, show that preparation of the present invention has significant analgesia role.

The analgesic activity (writhing method) of table 26 pair mice

2.6 influence to the myocardial ischemia experimentGet 50 of mices, be divided into 5 groups at random.That is: 10 every group, blank group, positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg).Successive administration l0.Fasting is 20 hours after administration in the 9th day, freely drinks water, and after the administration in the 10th day 40 minutes, each organized the equal subcutaneous injection isoprenaline of mice, after 15 minutes, mice is put into the 250ml ground wide mouthed bottle that the 15g sodica calx is housed, and observes mouse diing time.The results are shown in Table 27.Preparation high dose group of the present invention can obviously prolong the anoxybiotic time-to-live of mouse cardiac muscle, and with blank group P＜0.01 relatively, low dose group also shows better action trend, but does not relatively have difference on the statistics with positive controls.

The anoxybiotic influence of table 27 pair mouse cardiac muscle

2.7 Chinese People's Anti-Japanese Military and Political College's Mus myocardial ischemia effectGet 50 of rats, be divided into 5 groups at random: blank group, positive control sedative jujube kernel capsule group (2.7g/kg), preparation high dose group of the present invention (2.0g/kg), middle dosage group (1.0g/kg), low dose group (0.5g/kg).Every day gastric infusion, the blank group is irritated the ordinary water of stomach with volume, one week of continuous irrigation stomach, respectively at the 6th day and the 7th day lumbar injection isoprenaline after the administration, get blood then and on automatic clinical chemistry analyzer, measure the serum CPK value, the results are shown in Table 28.The result shows that the high, medium and low dosage group of preparation of the present invention all can reduce CPK value in the serum, with the blank group apparent property difference (P＜0.001) is arranged relatively, and its effect is better than sedative jujube kernel glue group.

The influence of table 28 pair rat blood serum creatine phosphokinase (CPK)

2.8 influence to the mouse anti-reflecting fatigue abilityGet 50 of mices, be divided into 5 groups at random: blank group, positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg).Successive administration 10 days, water is can't help in fasting 20 hours before the experiment, and administration next day dropped into (room temperature) in the ordinary water with mice after 30 minutes, carried out parallel observations, calculated from the beginning of falling into water with stopwatch and avaled to the nostril time of the water surface, the results are shown in Table 29.The result as seen, high, medium and low dosage group of preparation of the present invention and blank group contrast all can prolong the swimming time of mice, and antifatigue effect is arranged.

The influence of table 29 pair mouse anti-reflecting fatigue

2.9 influence to the mouse immune organGet 50 of mices, be divided into 5 groups at random: blank group, positive control sedative jujube kernel capsule group (4.5g/kg), preparation high dose group of the present invention (3.0g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg).Successive administration 10 days, the next day after the last administration, the eye socket sacrificed by exsanguination is got spleen, thymus is weighed, and represents with organ index, and t checks the significance of each group difference.The results are shown in Table 30.By table as seen, preparation of the present invention has tangible effect of gain to spleen and the thymus of mice, compares with the blank group, and significant difference (P＜0.001) is arranged.Its effect is better than the sedative jujube kernel capsule group.

The influence of table 30 pair mouse immune organ

3, conclusionDragon Fructus Jujubae capsule has tangible sedation, can reduce the autonomic activities number of times of white mice, strengthen the syngignoscism of pentobarbital sodium, obviously shorten the pentobarbital sodium dropping asleep latency, improve the sleeping rate of mice, prolong the length of one's sleep, strengthen the syngignoscism of chlorpromazine, improve the sleeping rate of chlorpromazine, can work in coordination with the central excitation effect of pentobarbital sodium antagonism caffeine and sodium benzoate.Also have significant analgesia role in addition, prolong the time-to-live of myocardial ischemia, function of resisting myocardial ischemia, antifatigue effect, enhance immunity effect etc.

By above Pharmacodynamic test of active extract, point out preparation of the present invention that mental sickness such as insomnia are had good preventive and therapeutic effect, for clinical application provides reference frame.

Five, toxicity test research

1, acute toxicity test

1.1 be subjected to the reagent thing: preparation medicated powder of the present invention, the sodium carboxymethyl cellulose with 1% are mixed with 20% suspension (be equivalent to every 100ml and contain crude drug 135g).

1.2 animal subject: white mice, male and female half and half, body weight 18～22g.

1.3 test method and result: according to the preliminary experiment result, expectation can not be measured LD ₅₀So, the mtd test of mensuration single-dose.Press the preparation suspension of the present invention of clinical administration approach gastric infusion 20% for 20 healthy mices, 0.8ml/20g dosage is 13.5g/kg, is equivalent to crude drug in whole 54g/kg, behave 200 times of clinical consumption per day (0.0675g/kg), animal activity reduces after the administration, and after about 2～3 hours, full recovery is normal, activity freely, behavior, diet, defecation show no obvious abnormalities, and continue to observe 14, do not have dead.

1.4 conclusion: the minimum lethal dose of preparation of the present invention is equivalent to 200 times of clinical people's consumption greater than the 54g/kg crude drug, shows that this medicine does not have the overt toxicity effect.

The present invention is further illustrated below in conjunction with the specific embodiment.

The specific embodiment

Embodiment 1: get Semen Pittospori Glabrati tea 12g, Radix Polygalae 8g, Radix Ophiopogonis 10g, Caulis Polygoni Multiflori 15g.Adding decocting becomes decoction to take.Usage and dosage: 1 dose of every day, divide clothes 3 times.

Embodiment 2: get Semen Pittospori Glabrati tea 12g, Radix Polygalae 8g, Radix Ophiopogonis 10g, Caulis Polygoni Multiflori 15g, Rhizoma valerianae latifoliae 10g, Fructus Crataegi 10g, Radix seu Herba Gei aleppici 10g.Adding decocting becomes decoction to take.Usage and dosage: 1 dose of every day, divide clothes 3 times.

Embodiment 3: get Semen Pittospori Glabrati tea 420g, Radix Polygalae 280g, Radix Ophiopogonis 350g, Caulis Polygoni Multiflori 525g.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 4: get Semen Pittospori Glabrati tea 8.4kg, Radix Polygalae 5.6kg, Radix Ophiopogonis 7kg, Caulis Polygoni Multiflori 10.5kg.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 20000, promptly gets tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 5: get Semen Pittospori Glabrati tea 708.75g, Radix Polygalae 236.25g, Radix Ophiopogonis 236.25g, Caulis Polygoni Multiflori 393.75g.Decoct with water 3 times, add 5 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, sheet once, 3 times on the one.

Embodiment 6: get Semen Pittospori Glabrati tea 157.5g, Radix Polygalae 315g, Radix Ophiopogonis 472.5g, Caulis Polygoni Multiflori 630g.Decoct with water 1 time, add 12 times in water, decocted 3 hours, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, and the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 7: get Semen Pittospori Glabrati tea 420g, Radix Polygalae 280g, Radix Ophiopogonis 350g, Caulis Polygoni Multiflori 525g.Decoct with water 3 times, add 8 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 1000, gets capsule of the present invention, specification: every dress 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 8: get Semen Pittospori Glabrati tea 168g, Radix Polygalae 112g, Radix Ophiopogonis 140g, Caulis Polygoni Multiflori 210g.Decoct with water 3 times, add 8 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, add right amount of auxiliary materials, mixing, granulate, drying is made the 300g(Sugarless type), the 1000g(sugar-containing type), promptly get granule of the present invention, specification: every packed 3g(Sugarless type), the 10g(sugar-containing type).Usage and dosage: oral, one time 1 bag, 3 times on the one.

Embodiment 9: get Semen Pittospori Glabrati tea 1682g, Radix Polygalae 1121g, Radix Ophiopogonis 1399g, Caulis Polygoni Multiflori 2098g.Decoct with water 2 times, add 10 times in water at every turn, decocted 2 hours at every turn, filter, merging filtrate, standing over night is got supernatant and is evaporated to about 800ml, adds right amount of auxiliary materials, and mixing adds water and makes 10000ml, promptly gets oral liquid of the present invention, specification: every bottled 10ml.Usage and dosage: oral, one time 1 bottle, 3 times on the one.

Embodiment 10: get Semen Pittospori Glabrati tea 4200g, Radix Polygalae 2800g, Radix Ophiopogonis 3500g, Caulis Polygoni Multiflori 5250g.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, it is 1.25～1.35(60 ℃ that filtrate decompression is concentrated into relative density) extractum, drying is ground into fine powder, adds right amount of auxiliary materials, grind well, be pressed into 10000, get soft capsule of the present invention, specification: every dress 0.4g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 11: get Semen Pittospori Glabrati tea 4200g, Radix Polygalae 2800g, Radix Ophiopogonis 3500g, Caulis Polygoni Multiflori 5250g.Decoct with water 2 times, add 12 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 10000, promptly gets tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 12: get Semen Pittospori Glabrati tea 8.4kg, Radix Polygalae 5.6kg, Radix Ophiopogonis 7.0kg, Caulis Polygoni Multiflori 10.5kg.Decoct with water 2 times, add 10 times in water at every turn, decocted 1.5 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 10000, gets capsule of the present invention, specification: every dress 0.25g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 13: get Semen Pittospori Glabrati tea 420g, Radix Polygalae 280g, Radix Ophiopogonis 350g, Caulis Polygoni Multiflori 525g, Rhizoma valerianae latifoliae 350g, Fructus Crataegi 350g, Radix seu Herba Gei aleppici 350g.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 14: get Semen Pittospori Glabrati tea 8400g, Radix Polygalae 5600g, Radix Ophiopogonis 7000g, Caulis Polygoni Multiflori 10500g, Rhizoma valerianae latifoliae 7000g, Fructus Crataegi 7000g, Radix seu Herba Gei aleppici 7000g.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 20000, promptly gets tablet of the present invention.Specification: every heavy 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 15: get Semen Pittospori Glabrati tea 1050g, Radix Polygalae 131.2g, Radix Ophiopogonis 262.5g, Caulis Polygoni Multiflori 393.8g, Rhizoma valerianae latifoliae 262.5g, Fructus Crataegi 262.5g, Radix seu Herba Gei aleppici 262.5g.Decoct with water 3 times, add 8 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 16: get Semen Pittospori Glabrati tea 131.2g, Radix Polygalae 341.1g, Radix Ophiopogonis 393.8g, Caulis Polygoni Multiflori 577.5g, Rhizoma valerianae latifoliae 393.8g, Fructus Crataegi 393.8g, Radix seu Herba Gei aleppici 393.8g.Decoct with water 1 time, add 12 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, it is an amount of to add starch, and mixing is granulated, drying, the adding magnesium stearate is an amount of, mixing, tabletting, coating is made 1000, promptly gets tablet of the present invention.Specification: every heavy 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 17: get Semen Pittospori Glabrati tea 420g, Radix Polygalae 280g, Radix Ophiopogonis 350g, Caulis Polygoni Multiflori 525g, Rhizoma valerianae latifoliae 350g, Fructus Crataegi 350g, Radix seu Herba Gei aleppici 350g.Decoct with water 2 times, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 1000, gets capsule of the present invention, specification: every dress 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 18: get Semen Pittospori Glabrati tea 840g, Radix Polygalae 560g, Radix Ophiopogonis 7000g, Caulis Polygoni Multiflori 10500g, Rhizoma valerianae latifoliae 7000g, Fructus Crataegi 7000g, Radix seu Herba Gei aleppici 7000g.Decoct with water 3 times, add 8 times in water at every turn, decocted 2 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 20000, gets capsule of the present invention, specification: every dress 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Execute example 19: get Semen Pittospori Glabrati tea 10500g, Radix Polygalae 1312.5g, Radix Ophiopogonis 2625g, Caulis Polygoni Multiflori 3937.5g, Rhizoma valerianae latifoliae 2625g, Fructus Crataegi 2625g, Radix seu Herba Gei aleppici 2625g.Decoct with water 3 times, add 10 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.20～1.25(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 10000, gets capsule of the present invention, specification: every dress 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Execute example 20: get Semen Pittospori Glabrati tea 1312.5g, Radix Polygalae 3411.5g, Radix Ophiopogonis 3937.5g, Caulis Polygoni Multiflori 5775g, Rhizoma valerianae latifoliae 3937.5g, Fructus Crataegi 3937.5g, Radix seu Herba Gei aleppici 3937.5g.Decoct with water 1 time, add 10 times in water at every turn, decocted 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.40(60 ℃) extractum, add right amount of auxiliary materials, mixing, drying is made 10000, gets capsule of the present invention, specification: every dress 0.45g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 21: get Semen Pittospori Glabrati tea 1680g, Radix Polygalae 1120g, Radix Ophiopogonis 1400g, Caulis Polygoni Multiflori 2100g, Rhizoma valerianae latifoliae 1400g, Fructus Crataegi 1400g, Radix seu Herba Gei aleppici 1400g.Decoct with water 3 times, add 8 times in water at every turn, decocted 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 ℃) extractum, add right amount of auxiliary materials, mixing, granulate, drying is made the 3000g(Sugarless type), the 10000g(sugar-containing type), promptly get granule of the present invention, specification: every packed 3g(Sugarless type), the 10g(sugar-containing type).Usage and dosage: oral, one time 1 bag, 3 times on the one.

Embodiment 22: get Semen Pittospori Glabrati tea 1680g, Radix Polygalae 1120g, Radix Ophiopogonis 1400g, Caulis Polygoni Multiflori 2100g, Rhizoma valerianae latifoliae 1400g, Fructus Crataegi 1400g, Radix seu Herba Gei aleppici 1400g.Decoct with water 2 times, add 10 times in water at every turn, decocted 2 hours at every turn, filter merging filtrate, standing over night, getting supernatant, to be evaporated to relative density be 1.15～1.20(60 ℃) extractum, add ethanol, make to contain the alcohol amount and reach 60%, left standstill 24 hours, and got supernatant, filter, be evaporated to about 8000ml, add right amount of auxiliary materials, mixing, add water and make 10000ml, promptly get oral liquid of the present invention, specification: every bottled 10ml.Usage and dosage: oral, one time 1 bottle, 3 times on the one.

Embodiment 23: get Semen Pittospori Glabrati tea 4200g, Radix Polygalae 2800g, Radix Ophiopogonis 3500g, Caulis Polygoni Multiflori 5250g, Rhizoma valerianae latifoliae 3500g, Fructus Crataegi 3500g, Radix seu Herba Gei aleppici 3500g.Decoct with water 3 times, add 8 times in water at every turn, decocted 1 hour at every turn, filter, it is 1.15～1.20(60 ℃ that filtrate decompression is concentrated into relative density) extractum, add ethanol, make to contain the alcohol amount and reach 60%, left standstill 24 hours, and got supernatant, filter, reclaiming ethanol and being concentrated into relative density is 1.25～1.30(60 ℃) extractum, vacuum drying is pulverized, sieve, add right amount of auxiliary materials, grind well, be pressed into 10000, promptly get soft capsule of the present invention, specification: every dress 0.4g.Usage and dosage: oral, one time 4,3 times on the one.

Embodiment 24: get Semen Pittospori Glabrati tea 840g, Radix Polygalae 560g, Radix Ophiopogonis 700g, Caulis Polygoni Multiflori 1050g, Rhizoma valerianae latifoliae 700g, Fructus Crataegi 700g, Radix seu Herba Gei aleppici 700g.Decoct with water 2 times, add 10 times in water at every turn, decocted 2 hours at every turn, filter merging filtrate, standing over night, getting supernatant, to be evaporated to relative density be 1.15～1.20(60 ℃) extractum, add ethanol, make to contain the alcohol amount and reach 60%, left standstill 24 hours, get supernatant, filter, being evaporated to relative density is 1.20(20 ℃) clear paste, spray drying, fine powder is standby; Add in the fused polyethylene glycol 6000, stir evenly, splash in the methyl-silicone oil, take out, drop pill is absorbed condensed fluid, and drying is made 10000, promptly gets drop pill of the present invention.Specification: every heavy 40mg.Usage and dosage: oral, one time 10,3 times on the one.

Embodiment 25: get Semen Pittospori Glabrati tea 1680g, Radix Polygalae 1120g, Radix Ophiopogonis 1400g, Caulis Polygoni Multiflori 2100g, Rhizoma valerianae latifoliae 1400g, Fructus Crataegi 1400g, Radix seu Herba Gei aleppici 1400g.Decoct with water 2 times, add 10 times in water at every turn, decocted 2 hours at every turn, filter merging filtrate, standing over night, getting supernatant, to be evaporated to relative density be 1.15～1.20(60 ℃) extractum, add ethanol, make to contain the alcohol amount and reach 60%, left standstill 24 hours, and got supernatant, filter, be evaporated to about 8000ml, add sucrose 100g, Mel 100g, sodium benzoate 2g, stir evenly, be heated to and boil, put to room temperature, add Fructus Citri tangerinae essence 1ml again, add water to 10000ml, stir evenly, filter, fill promptly gets syrup of the present invention, specification: every bottled 100ml.Usage and dosage: oral, a 10ml, 3 times on the one.

Embodiments of the present invention are not limited to the foregoing description, and the various variations of making under the prerequisite that does not break away from aim of the present invention all belong within protection scope of the present invention.

Claims (8)

1. prevent and treat the pharmaceutical preparation that insomnia waits mental sickness for one kind, it is characterized in that: it mainly is to be made by the crude drug of following weight ratio example: Semen Pittospori Glabrati tea 10%～45%, Radix Polygalae 15%～20%, Radix Ophiopogonis 15%～30%, Caulis Polygoni Multiflori 25%～40%.

2. according to the pharmaceutical preparation of mental sickness such as the described control insomnia of claim 1, it is characterized in that: the consumption of each crude drug is: Semen Pittospori Glabrati tea 26.7%, Radix Polygalae 17.8%, Radix Ophiopogonis 22.2%, Caulis Polygoni Multiflori 33.3%.

3. according to the pharmaceutical preparation of mental sickness such as the described control insomnia of claim 1, it is characterized in that: wherein crude drug also has Rhizoma valerianae latifoliae, Fructus Crataegi, Radix seu Herba Gei aleppici, and the part by weight of each crude drug is: Semen Pittospori Glabrati tea 5%～40%, Radix Polygalae 5%～13%, Radix Ophiopogonis 10%～15%, Caulis Polygoni Multiflori 15%～22%, Rhizoma valerianae latifoliae 10%～15%, Fructus Crataegi 10%～15%, Radix seu Herba Gei aleppici 10%～15%.

4. according to the described pharmaceutical preparation of controlling mental sickness such as control insomnia of claim 3, it is characterized in that: the consumption of each component is: Semen Pittospori Glabrati tea 16%, Radix Polygalae 10.7%, Radix Ophiopogonis 13.3%, Caulis Polygoni Multiflori 20%, Rhizoma valerianae latifoliae 13.3%, Fructus Crataegi 13.3%, Radix seu Herba Gei aleppici 13.3%.

5. the preparation method of the pharmaceutical preparation of mental sickness such as claim 1 or 2 described control insomnias, it is characterized in that: get Semen Pittospori Glabrati tea, Radix Polygalae, Radix Ophiopogonis, Caulis Polygoni Multiflori four Chinese medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～3 time, the each decoction 1～3 hour, filter, it is 1.20～1.40 extractum that filtrate is concentrated into 60 ℃ of relative densities, and preparation process is made different pharmaceutical preparation routinely then.

6. according to the preparation method of the pharmaceutical preparation of mental sickness such as the described control insomnia of claim 5, it is characterized in that: described pharmaceutical preparation is oral formulations, comprises decoction, granule, oral liquid, syrup, soft extract, pill, tablet, hard capsule or soft capsule.

7. the preparation method of the pharmaceutical preparation of mental sickness such as claim 3 or 4 described control insomnias, it is characterized in that: get Semen Pittospori Glabrati tea, Radix Polygalae, Radix Ophiopogonis, Caulis Polygoni Multiflori, Rhizoma valerianae latifoliae, Fructus Crataegi, Radix seu Herba Gei aleppici seven flavor medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～3 time, the each decoction 1～3 hour, filter, it is 1.20～1.40 extractum that filtrate is concentrated into 60 ℃ of relative densities, and preparation process is made different pharmaceutical preparation routinely then.

8. according to the preparation method of the pharmaceutical preparation of mental sickness such as the described control insomnia of claim 7, it is characterized in that: described pharmaceutical preparation is oral formulations, comprises decoction, granule, oral liquid, syrup, soft extract, pill, tablet, hard capsule or soft capsule.