CN100553652C - A kind of medicine of Cure for insomnia - Google Patents

Abstract

The invention provides a kind of medicine that is used for the treatment of insomnia, the present invention overcome the used adjuvant pure natural of present drop pill degree not high and at present the common chemical synthesis auxiliary material not in some national food additive catalogue, the relatively poor shortcoming of drop pill mouthfeel, be that a kind of natural degree is higher, the pharmaceutical preparation that safety is stronger, toxic and side effects is lower.

Description

A kind of medicine of Cure for insomnia

Technical field

The present invention relates to field of medicaments, particularly, relating to Chinese medicine is the preparation of the Cure for insomnia made of raw material.

Background technology

Along with socioeconomic fast development, the quickening of urbanization and aged tendency of population process, and the influence of factor such as competitive pressure, unemployment, rhythm of life variation, mental disorder is to the harm " more and more outstanding and serious " of Chinese people's health, cause various mental sickness such as insomnia, depression, neurosis, schizophrenia sharply to rise, because this disease sickness rate increases day by day, is called as " killer of new century ".Mental sickness more and more is subject to people's attention, and reason is that mental sickness not only endangers patient self health and lives, but also harm household and social security cause tremendous economic loss and bad social influence.Mental sickness comprises a variety of as insomnia, depression, neurosis, schizophrenia or the like.According to estimates, there are about 1,600 ten thousand people of serious psychiatric patient in the whole nation at present, has every year 250000 people to die from suicide approximately.Current neuropsychiatric disease ranks the first in the total burden of China's disease, has accounted for 20%, and therefore, mental sickness is a serious medical problem and social problem.Insomnia be a kind of lasting long duration sleep matter and/or measure situation unsatisfactory, often show as be difficult to fall asleep, can not fall asleep, keep dyskoimesis, too early or intermittence wake up and cause and do not have enough sleep.Insomnia is a kind of modal sleep disordered, almost everyone experience of ating fault and sleeping.Along with the development of society, the quickening of rhythm of life, insomnia's incidence rate is on the rise.According to statistics, the U.S., Europe and Australia have 10%～49% people to suffer from insomnia approximately, what had a sleepless night 20%～30% (comprising adult and child) in the population of the whole world has a strong impact on, and wherein 5% by due to the sleep disordered breathing, and severe patient can influence daily behavior and life.Short-term sleep restriction can cause carbohydrate tolerance to go down, and may be an independent hazard factor that is formed with symtomatic diabetes, does not have enough sleep to produce adverse effect to carbohydrate metabolism and endocrine function.Competent sleep except can allaying tiredness, also with human body immunity improving power, strengthen resist the disease ability closely related.

The traditional Chinese medical science is early on the books to insomnia, and " the puzzled greatly opinion of Ling Shu Miraculous Pivot or Divine Axis " discussed the pathogenesis of " unable to close the eyes " in more detail." the evil visitor of Ling Shu Miraculous Pivot or Divine Axis " piece of writing more proposes concrete method of treatment and square medicine to " unable to close the eyes ".The content that Chinese Zhang Zhongjing has enriched " interior warp " to the clinical syndrome of being insomnia and method of treatment, as: " SHAO YIN syndrome, more than two or three days, vexation must not crouch, the Chinese goldthread colla corii asini decoction master it." (" Treatise on Febrile Diseases is distinguished SHAO YIN syndrome arteries and veins card and controls ") " and the consumptive disease with restlessness insomnia, the suanzaoren decoction master it." two sides are still used always by clinical so far.Put down in writing some settling tranquilizers such as cinnabar, succinum in Tang's Sun Simiao " Qianjin Yi Fang volume one ", and on Rhizoma Pinelliae Sorghum vulgare Pers. soup basis, intended selecting treatments " restlessness of asrhenia type and insomnia greatly after being ill " such as WEIDANTANG, being insomnia for treatment since the Qin Han has increased new content.Propose clearly with the positive deficiency and excess of heresy as the dialectical outline of primary disease among the bright Zhang Jiebin " Jing Yue's complete work is rolled up 18 and is insomnia ", aspect treatment, he is according to the different syndromes of being insomnia, adopt different Therapeutic Principle and square medicine respectively, no matter on etiology and pathogenesis, or, still have higher reference value so far discussing the argumentation of controlling the system that all done in the medication.Bright Li Zhongzi " Required Readings for Medical Professionals volume ten must not crouch " also has much body and practicality to the cause of disease and the method for treatment argumentation of being insomnia.Brightly wear the opinion that first gift " key to Diagnosis and Treatment deficient door " has " year Gao Renyang declines and is insomnia ", illustrate that the cause of disease of being insomnia is relevant with yang deficiency, its argument quite merits attention.Thereafter doctor family is many is guidance with " interior warp ", " difficult ", " typhoid fever ", " gold is deficient " scheduling theory, in conjunction with the viewpoint of ancient Chinese medicine doctor and the clinical experience of oneself, all performances to some extent of aspect such as the cause of disease of demonstrate,proving being insomnia, pathogenesis, method of treatment, square medicine, thereby make the card of being insomnia, from theory into action, the understanding of comparison system has been arranged all.

The traditional Chinese medical science is divided into the flourishing type insomnia of heart-fire according to the characteristics of insomnia with insomnia, adopts the tranquilizing cinnabar pill for curing; Liver depression forming fire type aypnia adopts the Decoction of Gentiana for Purging the Liver-fire treatment; The WEIDANTANG treatment is adopted in the type of phlegm-heat attacking internally insomnia; The type of hyperactivity of fire caused by deficiency of YIN insomnia adopts LIUWEI DIHUANG WAN to close the Chinese goldthread colla corii asini decoction treatment; The GUIPI TANG treatment is adopted in the type of deficiency of both the heart and spleen insomnia; The type of deficiency of heart-QI and gallbladder-QI insomnia adopts the tranquilizing the mind ball to close the suanzaoren decoction treatment.Divided by the medicine-feeding beyond the region of objective existence, Chinese patent medicine commonly used at present also has Tianwang Buxin Dan, ANSHEN BUXIN WAN, kidney-brain-nourishing tablet, Yening Tangjiang, Baijiang Tablets, grow the heart-yin oral liquid, mind-easing tonic bolus with arborvitate seed, Naolejing, ANSHEN BUNAO YE, the nourishing blood to tranquillize the mind sheet, the succinum Anshen Wan, three BAODAN, red in the holy pillow in hole, Xuefu ecchymosis eliminating pill, Radix Et Caulis Acanthopanacis Senticosi tablet, yangxue anshen pills, Pill of Magnetitum and Cinnabari, the epilepsy medicine (Dianxianning) sheet, the valiant fighter is happy, the safe and comfortable oral liquid of sleeping, the sweet dreams oral liquid, BUZHONG YIQI WAN (sheet), Margarita powder, compound recipe Radix Schisandrae Bicoloris sheet, the Qiyeshen an sheet, FUFANG ZAOREN JIAONANG, brain invigorating liquid in the pillow, the reinforcing the heart sheet of allaying excitement, ANSHEN JIAONANG etc.Western medical treatment insomnia is main uses calm, hypnotic drug, and it mainly is divided into three major types: 1, benzodiazepine: this class drug main will have chlordiazepoxide, stabilizes, oxazepans, nitrodiazepam, tavor etc.2, barbiturates: this class medicine mainly contains phenobarbital, sodium phenobarbital etc.3, other miscellanies: as Paraldehyde, chloral hydrate, glutethimide, methaqualone, chlorpromazine, promethazine etc.Sleeping pill is that a class produces inhibitory action to the central nervous system, can cause calm and hypnotic medicine, and its sedation and syngignoscism there is no strict difference.

At present, the Chinese patent medicine of Cure for insomnia, used flavour of a drug are more, are difficult to control quality, the incompatibility industrialized great production of its medicine; In addition, mineral medicine or the Cinnabaris that adopt tranquillization with heavy prescription in Cure for insomnia, can cause damage to health again more in the Chinese patent medicine of Cure for insomnia; The dosage form of this type of medicine mostly is tablet, pill, oral liquid etc. in addition, the drug effect effect is slow, takes trouble.And all there is following problem in all at present Western medicine: 1, nearly all sleeping pill, long-term use continuously all can produce toleration and dependency.Suddenly drug withdrawal meeting produces symptoms such as thirsting for this medicine, irritability, insomnia, somatic tremor, perspiration, palpitating speed.2, this class medicine, especially action time long sedative hypnotic, with after carry over effect is often arranged, that inferior heliacal rising shows is dizzy, sleepy, lassitude, drowsy etc.Psychological test shows, takes after this type of medicine for 1 time in patient night, and second day afternoon, the response speed of measuring patient was obviously impaired, and I also am unaware of the existence of this infringement; This often forms potential danger for the people who is engaged in machine work.Therefore, the patient who takes medicine can not steering vehicle and operate machine, and to avoid accident.3, other central depressant things as antihistaminic, analgesic and ethanol etc., during with this class drug combination, can strengthen the inhibitory action to maincenter, particularly with the same time spent of ethanol, cental system are had coordinate repression, serious consequence can occur.4, barbiturates and two chlorals peace can not be used to suffer from the patient of acute intermittent hematoporphyria for the pyrrole beautiful jade.5, unsuitable for children uses sleeping pill, and intelligence is had side effect; For elderly patients, then should use cautiously, because confusion may occur after the medication.6, the careful usefulness of the hepatic and renal function person of going down, liver function serious hindrance person forbidding, especially barbiturates.7, women breast-feeding their children and anemia of pregnant woman are not suitable for using.

The synthetic chemical substance that modern medicine is commonly used has spreaded all over each corner of human lives, chemical synthetic drug becomes the main flow of medicine, yet, appearance along with multiple difficult serious symptom miscellaneous diseases, western medical treatment presents imperfect, the human lives and the healthy reality and the up-to-date successes achieved in research have all proposed query to this situation, particularly along with the continuous appearance of chemical drugs toxic and side effects, the change of spectrum of disease and conversion of medical, make modern medicine be subjected to unprecedented challenge, and people also place hope in the application and development of traditional medicine on gradually.Advocate back to nature, pay attention to plant amedica use, hanker after traditional remedies, the trend of advocating natural drug forms, making full use of natural materials is human best selections.

At present, in the world, natural drug all has certain market, along with people increasing and the aging of population to the health requirements level of understanding, sub-health stateization, people thirst for back to nature more, the problem of utilize the high Drug therapy of pure natural degree, preventing some chemical synthetic drugs cann't be solved, so the background that exceeds its original traditional national culture has been expanded in the application of natural plant.From natural drug, seek the little and inexpensive medicine of side effect and become the target that countries in the world pharmaceutical manufacturer is chased.The European Community has carried out unified legislation to medical herbs, state medical herbs status such as Canada and Australia have legalized, U.S. government has also drafted the plant amedica management method, the compound recipe mix preparation that begins to accept natural drug is as curative, and these provide good international environment for Chinese medicine enters international medical market as curative.On the other hand, along with the quickening of global economic integration progress, particularly China becomes a full member of WTO, and Chinese Medicine market incorporates the breadth and depth of international medical big market and will further aggravate.Face the enormous impact of Asian countries's traditional medicine product such as the keen competition of powerful transnational medical group and Japan, Korea S, India, Thailand and European countries' plant amedica such as Germany, France, numerous products that China's Chinese medicine produces are owing to still can not meet the standard of international medical market and requirement and being kept outside of the door.

Expansion and human back to nature requirement along with the market global range, use the low medicine of toxic and side effects, especially pure natural medical more and more becomes people's first-selection, dropping pill formulation be a kind of have efficient, quick-acting new medicine preparations, it has overcome the shortcoming and deficiency of Chinese medicine preparation in the past, but present dropping pill formulation generally faces following problem: 1, drop pill adjuvant pure natural degree is not high: at present, drop pill substrate adjuvant mostly is synthetic, natural degree is lower, the searching of new alternative substrate adjuvant, the searching of the alternative substrate adjuvant that particularly natural degree is high and preparation technology thereof determine, it is again very difficult thing, because the required preparation condition of at present common possible natural substrates adjuvant succedaneum is very harsh, it all is to influence the key that drop pill prepares molding that adjuvant temperature and drop pill thereof drip the system condition.The too high then viscosity of adjuvant melt temperature is low, and poor plasticity is though the adjuvant melt temperature is crossed lowplastcity by force, but drop pill has shortcomings such as easily sticking ball, distortion, therefore, seek pure natural degree height, and the adjuvant that is suitable for substituting existing drop pill substrate is a very job of hardships.2, the drop pill outlet encounters problems: along with expanding economy, more and more internationalize in market, China is also just making great efforts to adapt to this trend, present Chinese medicine dripping pills preparation as health food, successful export to many countries, but also face many problems at present, because different countries is different to the approval of the selected adjuvant of Chinese medicine dropping pill formulation, especially industrial flourishing Europe, more strict to food adjuvant and medical auxiliary materials, and as the selected chemosynthesis adjuvant (as Polyethylene Glycol) of the dropping pill formulation of health food outlet not in the catalogue of some national food additive, it is very unfavorable that this moves towards the international market to the Chinese medicine dropping pill formulation, becomes the stumbling-block that Chinese medicine enters the international market, therefore, seek the new of one or more, can be particularly important, also very urgent for the substrate adjuvant that the international market is accepted.3, the shortcoming of mouthfeel and onset speed: the mouthfeel of Chinese medicine and preparation thereof is relatively poor to be the big characteristics of one, people when taking some drugs to the frightened of disagreeable taste that its Chinese medicine had even be better than fear far away to disease, What is more, some patients are because can not overcome the poor taste of Chinese medicine or its preparation or abnormal smells from the patient and abandon the treatment of Chinese medicine, though can improve mouthfeel as medicine being made capsule or sugar coated tablet, reducing stimulates, but disintegration rate prolongs, be unfavorable for the rapid onset of medicine, to some disease, particularly need the disease of the rapid onset of medicine inapplicable.4, the preparation process difficulty of drop pill suitability for industrialized production: in the replacement process of dropping pill formulation adjuvant, determining of the preparation process of its suitability for industrialized production is very difficult something, as the ratio of the melt temperature of substrate adjuvant, the proportioning of dripping system temperature, adjuvant and medicine, dropper bore, condensing agent etc. all are the factors that influence drop pill, therefore, the replacement of substrate and to be suitable for suitability for industrialized production be a job consuming time, as to expend substantial contribution.

In order to change drop pill substrate adjuvant for a long time based on the situation of chemosynthesis adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and can not satisfy more and more that people require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect; Also can solve some problems that Chinese medicine preparation, particularly dropping pill formulation are run in exit procedure, strengthen the competitiveness of international market; The present invention has invented the pure Chinese medicine dripping pills preparation that a kind of toxic and side effects is low, evident in efficacy, moderate, adapt to industrialized great production by a large amount of tests and the research of preparation process.

Summary of the invention

The medicine that the purpose of this invention is to provide a kind of Cure for insomnia with new type natural substrate adjuvant preparation.

Another object of the present invention provides a kind of preparation method of Cure for insomnia pharmaceutical preparation.

The flat GUIXIN of drug selectivity sugariness of the present invention, Liver Channel have tranquilizing by nourishing the heart, and it is monarch drug that the Semen Ziziphi Spinosae of arresting sweating effect belongs to, and it can cure mainly heart-liver blood deficiency and cause restlessness of asrhenia type and insomnia, palpitation with fear palpitation with a distress feeling, excessive thirst, symptoms such as sweating due to debility.The flat bitter in the mouth of selectivity is nontoxic, and GUIXIN, Liver Channel have resolving stagnation for tranquilization, the appetizing of regulating the flow of vital energy, and the Flos Albiziae of the effect of activating collaterals to relieve pain is a ministerial drug, and it is uncomfortable in chest that it can cure mainly pent-up, and insomnia is forgetful, wind-fire ophthalmic, blurring of vision, pharyngalgia, carbuncle, diseases such as traumatic injury pain.Selecting the Radix Notoginseng total saponin from leaves is adjuvant drug, and according to the Compendium of Material Medica record, Folium Notoginseng cures mainly folding, and to hinder traumatic injury hemorrhage, and that applies promptly ends, and bruise promptly loose through night, the same root of its merit.The Radix Notoginseng total saponin from leaves is the effective ingredient of purifying through scientific method from stem and leaf of Radix Notoginseng, has purity height, the definite characteristics of stable curative effect.Modern pharmacology experiment showed, that saponin of Radix Notoginseng leaf has sedation, and the Radix Notoginseng total saponin from leaves can obviously suppress the spontaneous activity of mice, can make the animal peace and quiet, lies prostrate, blepharoptosis.The Radix Notoginseng total saponin from leaves has synergism to central depressant thing chlorpromazine, pentobarbital sodium, penthiobarbital: collaborative chlorpromazine is to the inhibitory action of mice autonomic activities; Collaborative pentobarbital sodium makes mice sleeping; Prolong the length of one's sleep of penthiobarbital significantly to mice.The Radix Notoginseng total saponin from leaves has antagonism to the excitement of the mice due to maincenter analeptic drug amfetamine, the caffeine.The mice convulsion that pentylenetetrazole and strychnine are caused has antagonism.Also have analgesia, cerebral ischemia protective effect in addition.The selection Radix Glycyrrhizae is a messenger drug, utilizes the effect of effect to strengthen the calmness of this prescription, to sleep peacefully of Radix Glycyrrhizae invigorating the spleen and replenishing QI, eliminating phlegm and stopping cough, heat-clearing and toxic substances removing, emergency analgesic therapy and the mediation property of medicine.

The selected substrate adjuvant of the present invention is resulting by a large amount of tests, it is little to have molecular weight, soluble in water, and molten diffusing speed is faster, pure natural degree height, toxic and side effects is low, and can reduce the medicine irritation abnormal smells from the patient, has the oral cavity of improvement acid-base value during the buccal of oral cavity, improve the characteristics of oral cavity smell, the used substrate adjuvant of the present invention is the agent of food sedan-chair flavor, takes that mouthfeel is good, the acceptant characteristics of patient, is the direction of following substrate adjuvant development.

Drug component of the present invention, the selection of consumption and adjuvant thereof also gropes to sum up to draw through the inventor in a large number, each amounts of components all has curative effect preferably in following ranges: 690～2070 parts of Semen Ziziphi Spinosaes, 414～1242 parts of Flos Albiziaes, 10.3～30 parts of saponin of Radix Notoginseng leaf, 207～621 parts in Radix Glycyrrhizae, appropriate amount of auxiliary materials is made, wherein adjuvant comprises filler and plasticity substrate, said filler is selected from the natural adjuvant of following one or more plant origins: erythritol, sorbitol, fructose, D-ribonic acid-gamma lactone, arabitol, trehalose, D-ribose, low melting-point agarose, Lac, xylitol, Raffinose, glucose, malic acid, citric acid, isomalt, lactose, maltose etc., and they contain the water of crystallization chemical compound; Said plasticity substrate is selected from the natural adjuvant of following one or more plant origins: starch and derivant thereof, cellulose and derivant thereof, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Described starch and derivant thereof such as pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch, described cellulose and derivant thereof such as methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose; Be chosen as 1035～1725 parts of the Semen Ziziphi Spinosaes, 621～1035 parts of Flos Albiziaes, 15.5～25.5 parts of saponin of Radix Notoginseng leaf, 310～517 parts in Radix Glycyrrhizae, appropriate amount of auxiliary materials of preferred drug component consumption of the present invention and adjuvant thereof are made, filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: sorbitol, xylitol, lactose, maltose, and they contain the water of crystallization chemical compound; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose; Be chosen as 1380 parts of the Semen Ziziphi Spinosaes, 828 parts of Flos Albiziaes, 20.7 parts of saponin of Radix Notoginseng leaf, 414 parts in Radix Glycyrrhizae, appropriate amount of auxiliary materials of best drug component consumption of the present invention and adjuvant thereof are made, and filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum.

Can also contain chemosynthesis adjuvant and animal origin adjuvant in the above-mentioned dressing, wherein filler comprises phenylglycol, hexadecanol, octadecanol, sodium stearate, tristerin, tripalmitin, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether; Wherein plasticity substrate comprises polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, gelatin.

In screening to above adjuvant, we find: plant colloid such as carrageenan, the tragakanta, pectin, agar, arabic gum, Ficus elastica, tamarind gum, locust bean gum, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, guar gum, Konjac glucomannan, it is big that plant colloids such as POLY-karaya have viscosity, mobile poor, characteristics such as do not solidify after the condensation, and arabic gum has high dense low sticking character, can be mixed with the aqueous solution of 50% concentration and still have flowability, this is one of not available characteristics of other hydrophilic colloid, arabic gum has at high temperature, under the low concentration, can ooze, but not condensation, at low temperature, under the high concentration, be difficult for oozing, but characteristics such as energy condensation.Polysaccharide such as polysaccharide such as starch and derivant thereof (as gelling starch, carboxymethyl starch etc.), cellulose derivative (as methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose etc.), alginic acid, dextrin, cyclodextrin, lactose, in screening, find alginic acid have viscosity big, be the fruit jelly sample, dextrin has the colloid sample; Characteristics such as lactose coagulability difference; And starch and derivant thereof are materials commonly used in the medical science adjuvant, thus in polysaccharide preferred starch and derivant thereof.Polyhydric alcohol such as sorbitol (88～102 ℃), xylitol (88～94.5 ℃), lactose (70～80 ℃), mannitol (166～169 ℃), maltose alcohol (135～140 ℃), isomalt polyhydric alcohol such as (98～103 ℃) screen, and find that it has following characteristics as drop pill substrate: sorbitol, lactose, isomalt are mobile poor; Mannitol, maltose alcohol fusing point are too high; The xylitol coagulability is poor slightly.After Preliminary screening, preferred xylitol, lactose, sorbitol in the selection of polyhydric alcohol, the best is an xylitol.Xylitol has following characteristics as drop pill substrate: in the time of 91 ℃, molten condition has appearred in xylitol, but not fusion fully, cooling rapidly, it separates out crystallization very soon, xylitol mixes the back good fluidity with extractum at certain proportion, can drip and can condensation, but be condensed into Powdered thing, loosely organized, the toughness extreme difference, that pinches is promptly broken.Organic acid and salt, alkali such as citric acid (100 ℃), sorbic acid (133 ℃), succinic acid (181～189 ℃), sodium acetate organic acid such as (58 ℃) and salt, alkali, its as drop pill substrate have fusing point too high, with Chinese medical concrete can't mixing etc. shortcoming.

Because of above single adjuvant existing shortcoming in as the drop pill preparation process, particularly we by above-mentioned Preliminary screening after, determine two kinds of adjuvants are used and screen: mainly be that above various adjuvants are carried out combined sorting, final determine following several: the plant colloid cooperates with the plant colloid, the cooperating of polyhydric alcohol and polyhydric alcohol, polyhydric alcohol and plant colloidally cooperate, the cooperating of the cooperating of xylitol and arabic gum, lactose and arabic gum, based on the composite auxiliary material of xylitol.Find preferred the cooperation to be xylitol, lactose and the compound use of other adjuvant, this kind combination has following characteristics: make up with mannitol: can drip not condensation; Make up with sorbic acid: both do not dissolve each other; Make up with lactose: can drip the energy condensation, but frangible; Make up with pomelo-pectin, tragakanta, sodium alginate: viscosity is big, can't drip; Make up with arabic gum: can drip, coagulability is poor slightly; Make up with dextrin: can drip, coagulability is poor slightly; Make up with starch: can drip, coagulability is also better.Determine that at last best of breed is that xylitol cooperates with arabic gum with starch, xylitol with starch, lactose.

At xylitol and starch, lactose and starch, in the research of xylitol and arabic gum combination, xylitol and starch Application of composite being prepared some required in the process of drop pill factors investigated, mainly is to the xylitol type, condensed fluid, condensate temperature influences the drop pill mouldability, xylitol and starch proportion influence mouldability, temperature is to the influence of drop pill mouldability, the extractum amount influences the drop pill mouldability, mixing time influences the drop pill mouldability, the dropper bore is to the influence of drop pill particle diameter, the formulation optimization of drop pill, the Preliminary Determination of drop pill, dissolve scattered time limit is investigated.Find that the solid xylitol has three types of powder, granular and crystallinity, and the easiest fusion of powder xylitol, again can fine dissolving be dispersed in the mixed liquor that starch, extractum forms, good fluidity, drippage is easy, and granular and crystalline xyhose alcohol is difficult for fusion, solubility property is also slightly poor, the mix flow that they and starch, extractum form is relatively poor, viscosity is very big, almost cannot drip, and therefore drips first-selected powder xylitol in the system process at drop pill.

At ratio of adjuvant molding is found in the sex research, in the combination of xylitol and starch, lactose and starch, xylitol and arabic gum, low melting point substrate adjuvant is 1: 0～1: 1.5 with the ratio of the weight of plasticity substrate adjuvant, be preferably 1: 0.1～1: 0.9, the best is 1: 0.1～1: 0.5.Low melting point substrate adjuvant of being formed within this scope and plasticity substrate adjuvant, the drug matrices fused solution all can ooze, and can condensation.Specific to each combination, xylitol is preferably 1: 0.2 with the ratio of the weight of starch～1: 0.3, and lactose is preferably 1: 0.2 with the ratio of the weight of starch～1: 0.3, and the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2～and 1: 0.4.Find that in the research of temperature temperature is big especially to the influence of drop pill mouldability to the influence of drop pill mouldability, when temperature is too low, owing to the too big effect that oozes that influences drop pill of viscosity of substrate, when temperature is too high, not condensation of drop pill.Find that in the extractum amount extractum amount is bigger to the influence of drop pill mouldability in to the sex research of drop pill molding, the extractum amount is too big, and made drop pill can not condensation, and the extractum amount is Xiao Yi holder tail too.Find that mixing time can have influence on the mouldability of drop pill in mixing time in to the sex research of drop pill molding, mixing time is too short, and mobile poor, influence oozes, and mixing time is oversize, influences the condensation of drop pill.Dripping under the system temperature, mixing time in 1～120 minute all can, suitable mixing time was at 10～30 minutes.Consider that mixing time can not be too short in the suitability for industrialized production, adopt the method that low temperature stirs for a long time, high temperature drips system.Find that in the research of dropper bore to the influence of drop pill particle diameter the dropper bore influences the size of drop pill and the flowability of fusion substrate, the system effect is dripped in influence.Drop pill diminishes and diminishes along with bore, but after 1.4 millimeters, along with the bore change of size that diminishes is not obvious, but the matrix flow reduction, system is dripped in influence.

Adopt orthogonal experimental method to be determined to Semen Ziziphi Spinosae, Flos Albiziae extraction conditions among the present invention

The water decoction that studies show that Semen Ziziphi Spinosae, Flos Albiziae has calmness, sedative action, so process using water extraction water soluble ingredient.According to the technological design thinking, investigated extraction time, quantity of solvent and extraction time 3 factors, every factor has been selected three horizontal design experiments, is index with the extraction total amount of Semen Ziziphi Spinosae saponin a, tests preferably, and experimental program sees Table 1.

Table 1 Semen Ziziphi Spinosae, Flos Albiziae extraction conditions quadrature factor level table

Alcohol precipitation concentration and concentrated volume are investigated

Different alcohol precipitation concentrations and spissated volume have very big influence to the extracted amount of effective ingredient, therefore experimental design with the first time alcohol precipitation concentration, concentrate volume before the precipitate with ethanol for the second time, alcohol precipitation concentration serves as to investigate index for the second time, divide three horizontal design experiments, extraction total amount with Semen Ziziphi Spinosae a is an index, and experimental program sees Table 2.

Table 2 alcohol precipitation concentration and concentrated volume quadrature factor level table

Semen Ziziphi Spinosae is our monarch drug among the present invention, and wherein Semen Ziziphi Spinosae saponin a is one of its main effective ingredient, so be that index is investigated orthogonal experiments with Semen Ziziphi Spinosae saponin a.

The drop pill Study on Preparation

We have done screening experiment to a system technology of tranquilizing dripping pill, investigate the ratio of extractum and adjuvant.Getting the substrate adjuvant of cream and different proportion (2,2.5,3,3.5,4,4.5,5,5.5 times of amounts) and change the gob ball respectively, is that index is investigated with drop pill hardness, appearance luster, drop pill roundness, the results are shown in Table 3.

Table 3 drop pill Study on Preparation

New substrate adjuvant	2 times	2.5 doubly	3 times	3.5 doubly	4 times	4.5 doubly	5 times	5.5 doubly
									The color and luster roundness	Color is evenly poor slightly, and special-shaped ball is arranged	The even rounding of color	The even rounding of color	The even rounding of color	The even rounding of color	The even rounding of color	The even rounding of color	Color is evenly poor slightly, and special-shaped ball is arranged
Hardness	Harder	Moderate	Moderate	Moderate	Moderate	Moderate	Moderate	Softer

Comprehensive The above results finally is defined as adding 2.5～5 times of new substrate adjuvants of amount of cream amount.

New substrate adjuvant is xylitol and starch or for lactose and starch or be the mixture of xylitol and arabic gum.

Through experiment confirm: the drop pill temperature is higher than 95 ℃, the drop pill excessive velocities, and condensation effect is poor, easily sticking ball, the roundness of drop pill is relatively poor sometimes; Be lower than 45 ℃, then drop pill speed is too slow, and the drop pill roundness is poor.Changing the material temperature is 45～115 ℃, and preferably changing the material temperature is 60～85 ℃, and optimization material temperature is 62～68 ℃; The system temperature is dripped in insulation: 45～95 ℃, it is 60～85 ℃ that the system temperature is dripped in preferred insulation, and it is 62～68 ℃ that the system temperature is dripped in best insulation, changes the material temperature a little more than dripping the system temperature; Liquid coolant is liquid paraffin, methyl-silicone oil or vegetable oil (Oleum Glycines, Semen Ricini wet goods), and the temperature of liquid coolant is-20～25 ℃, and dropper mouth internal diameter is 1.0～4.5 millimeters; Preferred condensing agent is liquid paraffin, methyl-silicone oil, and the condensing agent temperature is 0～18 ℃, and the dropper bore is 1.1～3.5 millimeters, and the difference of dropper mouth external diameter and internal diameter is less for well; Best condensing agent is 0～8 ℃ a methyl-silicone oil, drip a system temperature and be 62～68 ℃, dropper bore and be 1.2～2.5 millimeters,

Final definite system technology of dripping is: add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract in 2.5～5 times of amount adjuvants for total extractum, the abundant mixing, mixture is at 62～68 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, and insulation is in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splash in 0～8 ℃ the methyl-silicone oil, make drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Xylitol is a kind of natural plant sweetening agent, approve through World Health Organization (WHO), xylitol is a kind of safest sweeting agent, countries in the world are extensive use of in fields such as food and oral-cavity articles, xylitol enters the help that need not insulin in the cell, when sugar utilizes obstacle, can not cause blood sugar increasing yet, can improve diabetics symptom, have the ketoplastic effect of powerful inhibition, can promote the generation of liver glycogen, directly infiltrate the Developmental and Metabolic Disorder that tissue is participated in metabolism, can be corrected protein, fat and steroid; Xylose is the internal metabolism intermediate product, and body has higher toleration to it.Clinical practice proves: the highest oral dosis tolerata can reach 220g every day, and intravenous drip every day can reach 100g.The oral 25700mg/Kg of median lethal dose(LD 50) (LD50) mice, quiet notes 6400mg/Kg, the quiet notes of rat 6200mg/Kg.

Medicine mesostroma adjuvant of the present invention and amount of drug are than can being the scope that allows on the galenic pharmacy, medicine described here can be that crude drug also can be the effective ingredient extract, in order to adapt to industrialized great production, the ratio range of mesostroma adjuvant of the present invention and medicine refers to the weight proportion of adjuvant and extract drugs extractum, and the substrate adjuvant is 1: 0.1～1: 1 with the ratio of the weight of drug extract; Preferred substrate adjuvant is 1: 0.1～1: 0.6 with the ratio of the weight of extract drugs extractum; Best substrate adjuvant is 1: 0.2～1: 0.4 with the ratio of the extraction extractum weight of medicine.

Medicine of the present invention can adopt the preparation of Chinese medicine preparation conventional method.The preparation of effective ingredient of the present invention can be adopted following method: water extraction, decoction and alcohol sedimentation technique, extraction, infusion process, percolation, reflux extraction, continuous backflow extraction method, macroreticular resin absorbing method preparation.For example, these crude drug pulverize mix homogeneously can be made powder takes after mixing it with water; Also can be with these medicines decocting together, the condensed water decocting liquid is made oral liquid then; But, preferably adopt following technology to extract, but this can not limit protection scope of the present invention to raw material in order to make each crude drug of this medicine bring into play drug effect better.

The preparation method of medicine of the present invention is as follows:

(a) it is standby to get 690～2070 parts of Semen Ziziphi Spinosaes, 414～1242 parts of Flos Albiziaes, 10.3～30 parts of saponin of Radix Notoginseng leaf, 207～621 parts in Radix Glycyrrhizae;

(b) get Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae and add 6～14 times of crude drug water gagings, reflux, extract, 0.5～5 hour filters, filtrate for later use, medicinal residues add 6～14 times of crude drug water gagings, and reflux, extract, 0.5～5 hour filters, filtrate for later use, medicinal residues add 6～14 times of crude drug water gagings again, and reflux, extract, 0.5～5 hour filters, merge 3 times extracting solution, below 40～90 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 90～99% ethanol and make and contain the alcohol amount and reach 50～70%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 90～99% ethanol and make and contain the alcohol amount and reach 75～85%, standing over night filters, and filtrate decompression is concentrated into thick paste;

(c) in appropriate amount of auxiliary materials, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 45～115 ℃ of heating and meltings, mixing time is 1～120 minute, insulation is 1.0～4.5 millimeters at 40～115 ℃ of temperature following system, dropper bore, splashes in-20～25 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Preferred manufacturing procedure comprises the following steps:

(a) get 1035～1725 parts of Semen Ziziphi Spinosaes, 621～1035 parts of Flos Albiziaes, 15.5～25.5 parts of saponin of Radix Notoginseng leaf, 310～517 parts in Radix Glycyrrhizae;

(b) got 10～30 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 8～12 times of crude drug water gagings, reflux, extract, 1～3 hour filters filtrate for later use, medicinal residues add 8～12 times of crude drug water gagings, and reflux, extract, 1～3 hour filters, filtrate for later use, medicinal residues add 8～12 times of crude drug water gagings again, and reflux, extract, 1～3 hour filters, merge 3 times extracting solution, D below 60～80 ℃ ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, and filtrate recycling ethanol is at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 93～97% ethanol and make and contain the alcohol amount and reach 77～83%, standing over night filters, and filtrate is at D ₆₀=1.30～1.35 are evaporated to thick paste;

(c) in appropriate amount of auxiliary materials, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 60～85 ℃ of heating and meltings, mixing time is 10～30 minutes, insulation is 1.1～3.5 millimeters at 60～85 ℃ of temperature following system, dropper bore, splashes in 0～18 ℃ the liquid paraffin, methyl-silicone oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Best preparation method comprises the following steps:

(a) take by weighing 1380 parts of Semen Ziziphi Spinosaes, 828 parts of Flos Albiziaes, 20.7 parts of saponin of Radix Notoginseng leaf, 414 parts in Radix Glycyrrhizae by proportioning raw materials;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract in the adjuvant to doubly measuring for the 2.5-5 of total extractum, fully mix, mixture is at 62～68 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, and insulation is in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splash in 0～8 ℃ the methyl-silicone oil, make drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Best drop pill substrate adjuvant is xylitol and starch, and xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4.The substrate adjuvant is 1: 0.1～1: 1 with the ratio of the weight of medicine; Preferred substrate adjuvant is 1: 0.1～1: 0.6 with the ratio of the weight of medicine; Best substrate adjuvant is 1: 0.2～1: 0.4 with the ratio of the weight of medicine.

The best preparation method of medicine of the present invention is as follows:

(a) take by weighing 1380 parts of Semen Ziziphi Spinosaes, 828 parts of Flos Albiziaes, 20.7 parts of saponin of Radix Notoginseng leaf, 414 parts in Radix Glycyrrhizae by proportioning raw materials;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) to for the 2.5-5 of total extractum doubly measures, the ratio of weight is 1: 0.2～1: 0.3 xylitol and starch mixture; Or the ratio of weight is 1: 0.2～1: 0.3 lactose and starch mixture; Or the ratio of weight is to add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract in 1: 0.2～1: 0.4 xylitol and the arabic gum mixture, fully mix, mixture is at 62～68 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, insulation, at 62～68 ℃ of temperature following system, dropper bore is 1.2～2.5 millimeters, splash in 0～8 ℃ the liquid paraffin, methyl-silicone oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.

More than each single medicinal material, especially adjuvant drug, messenger drug or adjuvant drug and messenger drug in forming, can be replaced by suitable Chinese medicine individually or simultaneously with the identical property of medicine, effect, it is constant to replace back Chinese medicine preparation and drug effect thereof.

Medicine of the present invention can be determined usage and dosage according to patient's situation in use, but every day 1-3 time, and every day, each crude drug consumption was as the criterion with the state-promulgated pharmacopoeia dosage, was no more than the pharmacopeia ormal weight.

The drop pill that the present invention is prepared, conventional drop pill advantage is simple as preparing except having, steady quality, can make liquid medicine solidification, convenient drug administration, and efficient, quick-acting, its biggest advantage is:

1, the selected adjuvant pure natural of the present invention degree height: the substrate adjuvant that employed substrate adjuvant derives from natural plants or originates based on natural plants among the present invention, selected substrate adjuvant is xylitol and starch or lactose and starch or xylitol and arabic gum, this substrate adjuvant has pure natural degree height, toxic and side effects is low, mouthfeel is good, dissolve scattered time limit is short, rapid-action, it is a kind of new medium adjuvant, can be used for substituting present chemosynthesis substrate adjuvant, the drop pill made from this kind adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and more and more can not satisfy people and require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect.

2, some problems in the outlet of solution Chinese medicine: medicine of the present invention also can solve Chinese medicine preparation, some problems of in exit procedure, being run into of dropping pill formulation particularly, solve because different countries, especially the European countries of industry prosperity are to the difference identification of the selected adjuvant of Chinese medicine dropping pill formulation, overcome as the selected adjuvant Polyethylene Glycol of the dropping pill formulation of the health food outlet defective in some national food additive catalogue not, improve the Chinese medicine dripping pills preparation and move towards the international market, strengthen the competitiveness of international market.

3, solve the relatively poor problem of drop pill taste and further improve drug effect speed (dissolve scattered time limit): the medicinal dropping ball made from this kind substrate adjuvant of the present invention, can improve Chinese medicine preparation, the particularly present not good shortcoming of dropping pill formulation taste, improve mouthfeel, more easy for patients to accept, and the drop pill that adopts the selected adjuvant of medicine of the present invention to make has shorter dissolve scattered time limit, making drug effect faster, is a kind of onset medicine of Cure for insomnia faster.

4, higher safety and solve some problems in the drop pill storage process: the selected substrate of the present invention is not only additive, nutrient commonly used in the food industry, and can do medicinal, but do not see that it uses as the drug matrices adjuvant, therefore, with regard to substrate, be perfectly safe, have no side effect, a large amount of evidences, the drop pill that this adjuvant is made can reduce effective ingredient separating out in storage process, the sticking ball of drop pill, easy shortcomings such as moisture absorption deliquescing, but the big production of suitability for industrialized.

The present invention is under instruction of Chinese Medicine theory, preparation technology's test that process is a large amount of and pharmacology, the resulting preparation of pharmacodynamics test.The present invention is evident in efficacy, has nourshing blood and promoting blood circulation, the effect of benefiting vital QI for tranquillizing, be used for the treatment of various insomnia clinically, as the application in the medicines such as treatment insomnia due to pressure, bad hobby type insomnia, anxiety insomnia, depressive insomnia, mental sickness, depression, neurosis, schizophrenia, senile dementia, anxiety neurosis, obsession, borderline personality's obstacle, the neurasthenia, insomnia and dreamful sleep, diseases such as irritability.Be applicable to the preceding tension syndrome of neurasthenia and neurasthenic syndrome, insomnia cardiopalmus and migraine, nervous vascular Headache, neurosis headache, generalized anxiety disorder, climacteric syndrome, senile insufficient sleep, drug rehabilitation auxiliary treatment and student examination, rheumatic arthritis, senile dementia, chronic cerebral dysfunction syndrome, learning and memory ability obstacle, symptoms such as cerebral thrombosis, cerebral arteriosclerosis.Reasonable recipe of the present invention, poisonous side effect of medicine is low, has overcome that western medicine insomnia toxic and side effects is big, expense is high, the Chinese medicine curative effect is low, flavour of a drug are many, the shortcoming of incompatibility large-scale production, be a kind of economy, material benefit, curative effect definite medicine.In addition, used substrate adjuvant is the agent of food additive, sedan-chair flavor in the medicine of the present invention, have sweet taste but do not contain sugar, and rectifiable medicine irritation abnormal smells from the patient, and be applicable to diabetics.

In order to understand the present invention better, below with new substrate calm the nerves drip, drop pill soft durometer different, the sticking ball of drop pill with dissolve scattered time limit, the ball method of double differences of the tranquilizing dripping pill of making for the substrate adjuvant with the Polyethylene Glycol and newly the pharmacodynamics animal experiment of substrate tranquilizing dripping pill advantage of the present invention is described, test is intended to further specify the effect of tranquilizing dripping pill below, but not limitation of the present invention.The invention medicine that this experimental example adopts is to be prepared from by embodiment 1.

Test example 1: dissolve scattered time limit, the different contrast experiment's example of the ball method of double differences

In vitro tests

The present invention be that the tranquilizing dripping pill that adjuvant is made compares with the Polyethylene Glycol, by measuring dissolve scattered time limit, investigate its good releasing effect; By measuring indexs such as the ball method of double differences is different, whether ripe, whether be fit to suitability for industrialized production if investigating its preparation technology.

1. test medication: the new substrate tranquilizing dripping pill of the present invention (newly) is the tranquilizing dripping pill (old) that adjuvant is made with the Polyethylene Glycol.

2. method and result:

Dissolve scattered time limit: by " method is measured under this item of Chinese pharmacopoeia; The ball method of double differences is different: by " method is measured under this item of Chinese pharmacopoeia.Result of the test sees Table 1.

Three batches of tranquilizing dripping pills made from the new medium adjuvant of table 1 (newly) with the polyethylene glycol 6000 be tranquilizing dripping pill (old) dissolve scattered time limit made of adjuvant, weight differential relatively

Test data shows, the dissolve scattered time limit of new substrate tranquilizing dripping pill is lacking of the tranquilizing dripping pill made of adjuvant with the Polyethylene Glycol, different all being controlled in the pharmacopeia prescribed limit of the ball method of double differences of the tranquilizing dripping pill made from novel adjuvant.Presentation of results, the molten diffusing speed of the tranquilizing dripping pill made from novel adjuvant is faster, is more conducive to medicine and plays a role in the shortest time, and its ball method of double differences is different to be controlled in the pharmacopeia prescribed limit suitability for industrialized production.

Test example 2: the present invention with the polyethylene glycol 6000 be the sticking ball comparative observation of tranquilizing dripping pill soft durometer, drop pill that adjuvant is made

The present invention be that the tranquilizing dripping pill that adjuvant is made compares with the Polyethylene Glycol, by measuring indexs such as above-mentioned, investigate its effect.

1. test medication: the new substrate tranquilizing dripping pill of the present invention (newly) is provided by the Jinshili Medicine Research ﹠. Development Co., Ltd., Tianjin; With the Polyethylene Glycol is the tranquilizing dripping pill (old) that adjuvant is made, and is provided by the Jinshili Medicine Research ﹠. Development Co., Ltd., Tianjin.

2. method and result:

Get three batches of new, old substrate tranquilizing dripping pills, be loaded in the porcelain vase respectively, and use the bottle stopper good seal.Putting it into the bottom has in the exsiccator of saturated Nacl (humidity 75%) solution, exsiccator is put into 40 ℃ of drying baker of constant temperature again, and timing sampling is observed situations such as drop pill soft durometer, the sticking ball of drop pill, the results are shown in Table 2.1, table 2.2.

Three batches in table 2.1 is that the tranquilizing dripping pill reserved sample observing that adjuvant is made compares with the polyethylene glycol 6000

Table 2.2: three batches of tranquilizing dripping pills made from the new medium adjuvant (newly) with the polyethylene glycol 6000 be tranquilizing dripping pill (old) character observation made of adjuvant relatively

Result of the test shows, the drop pill soft durometer of new substrate tranquilizing dripping pill changes and be that the tranquilizing dripping pill made of adjuvant is similar, strong slightly with the Polyethylene Glycol; The sticking ball variation of the drop pill of new substrate tranquilizing dripping pill, firmness change and be that the tranquilizing dripping pill made of adjuvant is similar with the Polyethylene Glycol.Presentation of results, the sticking ball of the tranquilizing dripping pill that new, old substrate adjuvant is made changes, firmness change is similar, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, but suitability for industrialized production.

The Pharmacodynamic test of active extract of tranquilizing dripping pill

Test objective

Study the pharmacodynamics of new substrate tranquilizing dripping pill, in the hope of the experimental basis of science is provided for this medicine.

Be subjected to the reagent thing

1. the tranquilizing dripping pill fluid extract provides the suitable crude drug 7.6g of every gram cream, lot number: 20011015 by Tianjin Tasy Pharmaceutical Group Co., Ltd's development.Preserve in the stock solution refrigerator, before test, take out, be made into debita spissitudo, for the animal gastric infusion with distilled water.

Mouse test is selected dosage for use: 10g crude drug/kg, 5g crude drug/kg, 2.5g crude drug/kg, 1.25g crude drug/kg.

Mice administration concentration: 0.316g crude drug/ml, 0.158g crude drug/ml, 0.079g crude drug/ml, 0.0395g crude drug/ml.

Mice administration volume: 0.32ml/10g.

Rat test is selected dosage for use: 5g crude drug/kg, 2.5g crude drug/kg, 1.25g crude drug/kg.

The rat administration concentration: 0.5g crude drug/ml, 0.25g crude drug/ml, 0.125g crude drug/ml,

Rat administration volume: 1ml/100g

2. positive control drug:

(1) YIXING NINHSHEN PIAN: the Heng Ren of Liaoning Province pharmaceutcal corporation, Ltd produces, lot number; 000501.

Dosage: 1.58g powder/kg

Mice administration concentration: 0.049g powder/ml, mice administration volume: 0.32ml/10g

Rat administration concentration: 0.156g powder/ml, rat administration volume: 1ml/100g.

(2) stable: people pharmaceutical factory of Tianjin aminoacid company produces, lot number: 001120.

Dosage: 5mg/kg, mice administration concentration: 0.2mg/ml, administration volume: 0.25ml/10g.

3. instrument medicine:

Pentobarbital sodium: China Medicine's import packing, lot number; 971104

Compound concentration: 3mg/ml, administration volume: 0.1ml/10g.Dosage 30mg/kg

4mg/ml, administration volume: 0.1ml/10g.Dosage 40mg/kg

Caffeine: lot number 00011109 is provided by Tianjin Tasy Pharmaceutical Group Co., Ltd.

Compound concentration 0.5mg/ml, administration volume 0.1ml/10g.Dosage 5mg/kg.

Laboratory animal

1. Kunming mouse, about body weight 20 (g), the male and female dual-purpose.

2.Wistar plant rat, about body weight 200g, the male and female dual-purpose.

Provide the quality certification by the production of Tianjin Inst. of Materia Medica animal housing: No. 001, the accurate word of the real kinoplaszm R in W-J Tianjin.Raising is in having the observation ward of central air-conditioning, and the full nutrition piece material that feedstuff is produced for the calibrating of Chinese biological goods is drunk tap water.

Experimental apparatus

1.Jzz98 the autonomic activities analyzer, institute of materia medica, medical courses in general institute Beijing produces.

2. the special AC-T blood-counter system of Ku Er: Beckman company produces.

3.LBY-N6 blood viscosity instrument: Beijing Puli gives birth to company and produces.

4. microscope, enumerator etc.

Test method and result

One. calm test

1. to the influence (autonomic activities instrument method) of mice autonomic activities

60 mices are selected in test for use, and male and female half and half are divided into 6 groups at random: (1) matched group, and the filling stomach gives the distilled water with volume; (2) stable group is in preceding 1 the gastric infusion 5mg/kg dosage of test; (3) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg; (4) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 10g crude drug/kg dosage; (5) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 5g crude drug/kg dosage; (6) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 2.5g crude drug/kg dosage.Except that (2) group, all the other respectively organize gastric infusion 1 time every day, give 3 days continuously.After the last administration 40 minutes, every mice is placed Jzz98 autonomic activities instrument (production of institute of materia medica, medical courses in general institute Beijing) respectively, treat that it adapts to 5 minutes, write down mice autonomic activities number of times in 5 minutes then, the average and the matched group average of administration group are carried out statistics T test, result's (seeing Table 1) shows that the new substrate tranquilizing dripping pill of 10g crude drug/kg, 5g crude drug/kg dosage can reduce mice autonomic activities number of times significantly, has sedation preferably.

The new substrate tranquilizing dripping pill of table 1. is to the influence of mice autonomic activities

^*p＜0.05 ^**p＜0.01 ***p＜0.001

2. to the influence of spontaneous activity in mice (walk about time and lift two forelimb methods)

50 mices are selected in test for use, and male and female half and half are divided into 5 groups at random: (1) matched group, and the filling stomach gives the distilled water with volume; (2) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg; (3) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 10g crude drug/kg dosage; (4) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 5g crude drug/kg dosage; (5) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 2.5g crude drug/kg dosage.Every day, gastric infusion was 1 time, give 3 days continuously, after the last administration 40 minutes, every mice is positioned over respectively in the plastic casing of 50 * 30 * 15 (cm), make it adapt to 2 minutes, write down the time of walking about in 2 minutes then and praise two forelimb number of times, administration class mean and matched group average are carried out statistics T test, result's (seeing Table 2) shows that new substrate tranquilizing dripping pill can reduce the time of walking about of mice very significantly and praise two forelimb number of times.

The influence that the new substrate tranquilizing dripping pill of table 2. is walked about the time and lifted two forelimb number of times mice

^**p＜0.01 ^***p＜0.001

3. to the antagonism of caffeine

70 mices are selected in test for use, and male and female half and half are divided into 7 groups at random: (1) normal control group, and the filling stomach gives the distilled water with volume; (2) model control group, the filling stomach gives the distilled water with volume; (3) stable group is in preceding 1 gastric infusion of test, 5mg/kg dosage; (4) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg; (5) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 5g crude drug/kg dosage medicinal liquid; (6) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 2.5g crude drug/kg dosage medicinal liquid; (7) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 1.25g crude drug/kg dosage medicinal liquid.Except that the 3rd group, all the other respectively organize gastric infusion 1 time every day, give 3 days continuously.After the last administration 25 minutes, except that the normal control group, all the other respectively organize the caffeine of lumbar injection 5mg/kg, after 10 minutes, every mice is placed Jzz98 autonomic activities instrument (production of institute of materia medica, medical courses in general institute Beijing) respectively, treat that it adapts to 5 minutes, write down mice autonomic activities number of times in 5 minutes then, the average and the model control group average of administration group are carried out statistics T test, result's (seeing Table 3) shows, each administration group all can reduce mice autonomic activities number of times significantly, shows that new substrate tranquilizing dripping pill has certain antagonism to caffeine.

The new substrate tranquilizing dripping pill of table 3 is to the antagonism of caffeine

^*Expression administration group and model control group are relatively ^*P＜0.05 ^*P＜0.01

△ representation model matched group and normal control group be p＜0.05 relatively

Two. the sleep test

1. to the synergism of pentobarbital sodium sub-threshold dose

60 mices are selected in test for use, and male and female half and half are divided into 6 groups at random: (1) matched group, and the filling stomach gives the distilled water with volume; (2) stable matched group, gastric infusion before testing 1 time, 5mg/kg dosage; (3) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg dosage medicinal liquid; (4) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 5g crude drug/kg dosage medicinal liquid; (5) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 2.5g crude drug/kg dosage medicinal liquid; (6) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 1.25g crude drug/kg dosage medicinal liquid.Except that the 2nd group, all the other respectively organize gastric infusion 1 time every day, give 3 days continuously, after the last administration 40 minutes, each organizes the pentobarbital sodium of lumbar injection 30mg/kg dosage, write down mice sleep number of elements in 15 minutes (with righting reflex loss more than 1 minute the person be sleep), the sleep number of animals of administration group is compared with matched group, carry out x ²Test, result's (seeing Table 4) shows that relatively there were significant differences for 5g crude drug/kg, 2.5g crude drug/kg dosage group and matched group, shows that new substrate tranquilizing dripping pill and pentobarbital sodium have the obvious synergistic effect.

The new substrate tranquilizing dripping pill of table 4. is to the synergism of pentobarbital sodium sub-threshold dose

^*p＜0.05 ^**p＜0.01

2. to the influence of the length of one's sleep of threshold dose pentobarbital sodium

50 mices are selected in test for use, and male and female half and half are divided into 5 groups at random: (1) matched group, and the filling stomach gives the distilled water with volume; (2) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg dosage medicinal liquid; (3) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 10g crude drug/kg dosage medicinal liquid; (4) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 5g crude drug/kg dosage medicinal liquid; (5) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 2.5g crude drug/kg dosage medicinal liquid.Every day, gastric infusion was 1 time, give 3 days continuously, after the last administration 40 minutes, each organizes the pentobarbital sodium of lumbar injection 40mg/kg dosage, the record mice after giving pentobarbital sodium sleep incubation period and the length of one's sleep (if the length of one's sleep above 30 minutes, in 30 minutes), each administration class mean and matched group are relatively, carry out statistics T test, result's (seeing Table 5) shows, high dose group can obviously shorten mice pentobarbital sodium sleep incubation period and prolong its length of one's sleep, in, low dose group then only prolongs the length of one's sleep of mice.Show that new substrate tranquilizing dripping pill has certain influence to the sleep of mice.

The new substrate tranquilizing dripping pill of table 5. is to the influence of the length of one's sleep of mice pentobarbital sodium

^*p＜0.05 ^**p＜0.01 ^***p＜0.001

3. to the sleeping again influence of threshold dose pentobarbital sodium sleep mice

50 mices are selected in test for use, and male and female half and half are divided into 5 groups at random: (1) matched group, and the filling stomach gives the distilled water with volume; (2) positive drug group is irritated stomach and is given YIXING NINHSHEN PIAN 1.58g powder/kg dosage medicinal liquid; (3) new substrate tranquilizing dripping pill high dose group is irritated stomach and is given 10g crude drug/kg dosage medicinal liquid; (4) dosage group in the new substrate tranquilizing dripping pill is irritated stomach and is given 5g crude drug/kg dosage medicinal liquid; (5) new substrate tranquilizing dripping pill low dose group is irritated stomach and is given 2.5g crude drug/kg dosage medicinal liquid.Every day, gastric infusion was 1 time, give 3 days continuously, after the last administration 40 minutes, each organizes the pentobarbital sodium of lumbar injection 40mg/kg dosage, observe and record sleep mice sleeping once more number of animals after reviving (reach with righting reflex loss the person is sleep more than 1 minute), each group reenters the number of animals of sleeping and compares with matched group, carry out the x2 test, result's (seeing Table 6) shows, 5g crude drug/kg dosage group and matched group relatively have significant difference, show that new substrate tranquilizing dripping pill has certain facilitation to falling asleep again of threshold dose pentobarbital sodium sleep mice.

The new substrate tranquilizing dripping pill of table 6. is to the sleeping again influence of threshold dose pentobarbital sodium sleep mice

^**p＜0.01

The specific embodiment

Embodiment 1

(a) get Semen Ziziphi Spinosae 1380g, Flos Albiziae 828g, saponin of Radix Notoginseng leaf 20.7g, Radix Glycyrrhizae 414g, xylitol 260g, starch 40g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) with xylitol and starch mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 62～68 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splashes in 0～8 ℃ the methyl-silicone oil, make the 1000g drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 2

(a) get Semen Ziziphi Spinosae 1380g, Flos Albiziae 828g, saponin of Radix Notoginseng leaf 20.7g, Radix Glycyrrhizae 414g, lactose 260g, starch 40g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 8 times of crude drug water gagings, reflux, extract, 3 hours filters filtrate for later use, medicinal residues add 8 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 6 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) lactose and starch are mixed, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 62～68 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splashes in 0～8 ℃ the methyl-silicone oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 3

(a) get Semen Ziziphi Spinosae 690g, Flos Albiziae 500g, saponin of Radix Notoginseng leaf 12g, Radix Glycyrrhizae 250g, xylitol 280g, arabic gum 50g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) xylitol and arabic gum are mixed, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract in the mixture, fully mix, mixture stirs at 80～95 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splashes in 0～8 ℃ the liquid paraffin, make the 1000g drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 4

(a) get Semen Ziziphi Spinosae 2070g, Flos Albiziae 1000g, saponin of Radix Notoginseng leaf 25g, Radix Glycyrrhizae 500g, erythritol 30g, xylitol 300g, xanthan gum 25g is standby;

(b) get Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae and add 14 times of crude drug water gagings, reflux, extract, 5 hours filters, filtrate for later use, medicinal residues add 12 times of crude drug water gagings, and reflux, extract, 3 hours filters, filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, and reflux, extract, 1 hour filters, merge 3 times extracting solution, below 60～80 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 90～99% ethanol and make and contain the alcohol amount and reach 60～65%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 90～99% ethanol and make and contain the alcohol amount and reach 75～85%, standing over night filters, and filtrate decompression is concentrated into thick paste;

(c) with erythritol, xylitol 300g, xanthan gum mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 55～68 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, in following system of 62～68 ℃ of temperature, the dropper bore is 1.21～2.5 millimeters, splashes in 0～8 ℃ the vegetable oil, make the 1000g drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 5

(a) get Semen Ziziphi Spinosae 1035g, Flos Albiziae 621g, saponin of Radix Notoginseng leaf 15.5g, Radix Glycyrrhizae 310g, lactose 450g, Lac 80g, carrageenan 50g is standby;

(b) got 25 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2.5 hours filters filtrate for later use, medicinal residues add 8 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, D below 80 ℃ ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, and filtrate recycling ethanol is at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 93～97% ethanol and make and contain the alcohol amount and reach 77～83%, standing over night filters, and filtrate is at D ₆₀=1.30～1.35 are evaporated to thick paste;

(c) with lactose, Lac, carrageenan mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 85 ℃ of heating and meltings, and mixing time is 10～30 minutes, insulation, in following system of 80 ℃ of temperature, the dropper bore is 1.7 millimeters, splashes in 0～18 ℃ the liquid paraffin, make the 1000g drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 6

(a) get Semen Ziziphi Spinosae 1725g, Flos Albiziae 1000g, saponin of Radix Notoginseng leaf 20.5g, Radix Glycyrrhizae 517g, tragakanta 54g, sorbitol 302g are standby;

(b) got 20 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 12 times of crude drug water gagings, reflux, extract, 3 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2.5 hours filters, filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, and reflux, extract, 2.5 hours filters, merge 3 times extracting solution, D below 70 ℃ ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, and filtrate recycling ethanol is at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate is at D ₆₀=1.30～1.35 are evaporated to thick paste;

(c) with tragakanta, sorbitol mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 60 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, in following system of 58 ℃ of temperature, the dropper bore is 2.0 millimeters, splashes in 5～10 ℃ the methyl-silicone oil, make the 1000g drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 7

(a) get Semen Ziziphi Spinosae 800g, Flos Albiziae 515g, saponin of Radix Notoginseng leaf 12.5g, Radix Glycyrrhizae 220g, xylitol 259g, alginic acid 167g, chitin 40g is standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 80 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) get xylitol, alginic acid, chitin mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture is at 90 ℃ of heating and meltings, stir, mixing time is 8 minutes, insulation, at 85 ℃ of temperature following system, dropper bore is 1.1 millimeters, splash in 0～18 ℃ the liquid paraffin, make the 1000g drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 8

(a) get Semen Ziziphi Spinosae 700g, Flos Albiziae 1242g, saponin of Radix Notoginseng leaf 25g, Radix Glycyrrhizae 621g, xylitol 350g, Lac 260g, starch 25g is standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) get xylitol, Lac, starch mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture is at 115 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, insulation, at 95 ℃ of temperature following system, dropper bore is 1.2～1.6 millimeters, splash in 8～13 ℃ the liquid paraffin, methyl-silicone oil, make the 1000g drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 9

(a) get Semen Ziziphi Spinosae 850g, Flos Albiziae 350g, saponin of Radix Notoginseng leaf 17.5g, Radix Glycyrrhizae 300g, xylitol 400g, xanthan gum 100g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 8 times of crude drug water gagings, reflux, extract, 3 hours filters filtrate for later use, medicinal residues add 8 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 6 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) get saponin of Radix Notoginseng leaf dry powder and add Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, heating in water bath makes dissolving, and mix homogeneously adds xylitol, xanthan gum mixtures, 80～95 ℃ of change material are even, insulation is 1.0～4.5 millimeters at 40～95 ℃ of temperature following system, dropper bore, splashes in refrigerative 6～8 ℃ of methyl-silicone oils, make the 1000g drop pill, take out, clean, promptly.

Embodiment 10

(a) get Semen Ziziphi Spinosae 1850g, Flos Albiziae 750g, saponin of Radix Notoginseng leaf 15g, Radix Glycyrrhizae 310g, xylitol 260g, starch 40g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 8 times of crude drug water gagings, reflux, extract, 3 hours filters filtrate for later use, medicinal residues add 8 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 6 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 70 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) get xylitol and starch mix homogeneously, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture is at 100 ℃ of heating and meltings, stir, mixing time is 6 minutes, insulation, at 45 ℃ of temperature following system, dropper bore is 3.5 millimeters, splash in-20～25 ℃ the methyl-silicone oil or vegetable oil, make the 1000g drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Embodiment 11

(a) get Semen Ziziphi Spinosae 690g, Flos Albiziae 414g, saponin of Radix Notoginseng leaf 10.3g, Radix Glycyrrhizae 207g, xylitol 560g, starch 240g are standby;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 7 times of crude drug water gagings, reflux, extract, 3 hours filters filtrate for later use, medicinal residues add 6 times of crude drug water gagings, and reflux, extract, 2.5 hours filters, filtrate for later use, medicinal residues add 5 times of crude drug water gagings again, and reflux, extract, 2 hours filters, merge 3 times extracting solution, below 75 ℃, D ₆₀=1.06～1.09 are evaporated to 1g crude drug/ml, add 95% ethanol and make and contain alcohol amount and reach 60%, and standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) get xylitol, starch mixing, in mixture, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture is at 62～68 ℃ of heating and meltings, stir, mixing time is 1～120 minute, insulation, at 62～68 ℃ of temperature following system, dropper bore is 1.20～2.5 millimeters, splash in 0～5 ℃ the liquid paraffin, make the 1000g drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.

Claims (12)

1, a kind of medicine of Cure for insomnia, it is characterized in that: it is to be that crude drug adds that appropriate amount of auxiliary materials makes by 207～621 parts of 690～2070 parts of Semen Ziziphi Spinosaes, 414～1242 parts of Flos Albiziaes, 10.3～30 parts of saponin of Radix Notoginseng leaf, Radix Glycyrrhizae by weight, wherein adjuvant is made up of filler and plasticity substrate, and said filler is selected from the natural adjuvant of following one or more plant origins: erythritol, sorbitol, fructose, trehalose, Lac, xylitol, isomalt, lactose, maltose; Said plasticity substrate is selected from the natural adjuvant of following one or more plant origins: starch and derivant thereof, cellulose and derivant thereof, arabic gum, chitin, carrageenan, tragakanta, xanthan gum, alginic acid, dextrin, cyclodextrin, agar, lactose; Described starch and derivant thereof are pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch, and described cellulose and derivant thereof are methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose.

2, about thing of Cure for insomnia as claimed in claim 1, it is characterized in that: it is to be that crude drug adds that appropriate amount of auxiliary materials makes by 310～517 parts of 1035～1725 parts of Semen Ziziphi Spinosaes, 621～1035 parts of Flos Albiziaes, 15.5～25.5 parts of saponin of Radix Notoginseng leaf, Radix Glycyrrhizae by weight, and filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: sorbitol, xylitol, lactose, maltose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose.

3, the medicine of Cure for insomnia as claimed in claim 1, it is characterized in that: it is to be that crude drug adds that appropriate amount of auxiliary materials makes by 414 parts of 1580 parts of Semen Ziziphi Spinosaes, 828 parts of Flos Albiziaes, 20.7 parts of saponin of Radix Notoginseng leaf, Radix Glycyrrhizae by weight, and filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum.

4, the medicine of Cure for insomnia as claimed in claim 3 is characterized in that described adjuvant is xylitol and starch, and xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch.

5, the medicine of Cure for insomnia as claimed in claim 3 is characterized in that described adjuvant is lactose and starch, and lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch.

6, the medicine of Cure for insomnia as claimed in claim 3 is characterized in that described adjuvant is xylitol and arabic gum, and the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4.

7,, it is characterized in that adjuvant and the ratio that crude drug extracts the weight of extractum are 1: 0.1～1: 1 as the medicine of claim 1,2 or 3 described Cure for insomnias.

8,, it is characterized in that adjuvant and the ratio that crude drug extracts the weight of extractum are 1: 0.1～1: 0.6 as the medicine of claim 1,2 or 3 described Cure for insomnias.

9,, it is characterized in that adjuvant and the ratio that crude drug extracts the weight of extractum are 1: 0.2～1: 0.4 as the medicine of claim 1,2 or 3 described Cure for insomnias.

10, the preparation method of claim 1,2 or 3 described Cure for insomnia medicines is characterized in that this method comprises the steps:

(a) it is standby to get 690～2070 parts of Semen Ziziphi Spinosaes, 414～1242 parts of Flos Albiziaes, 10.3～30 parts of saponin of Radix Notoginseng leaf, 207～621 parts in Radix Glycyrrhizae;

(b) get Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae and add 6～14 times of crude drug water gagings, reflux, extract, 0.5～5 hour filters, filtrate for later use, medicinal residues add 6～14 times of crude drug water gagings, reflux, extract, 0.5～5 hour, filter, filtrate for later use, medicinal residues add 6～14 times of crude drug water gagings again, reflux, extract, 0.5～5 hour, filter, merge 3 times extracting solution, 40～90 ℃ are evaporated to 1g crude drug/ml, measure D ₆₀=1.06～1.09, add 90～99% ethanol and make and contain the alcohol amount and reach 50～70%, standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 90～99% ethanol and make and contain the alcohol amount and reach 75～85%, standing over night filters, and filtrate decompression is concentrated into thick paste;

(c) in appropriate amount of auxiliary materials, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 45～115 ℃ of heating and meltings, mixing time is 1～120 minute, insulation is 1.0～4.5 millimeters at 40～95 ℃ of temperature following system, dropper bore, splashes in-20～25 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

11, the preparation method of Cure for insomnia medicine as claimed in claim 10 is characterized in that this method comprises the steps:

(a) get 1035～1725 parts of Semen Ziziphi Spinosaes, 621～1035 parts of Flos Albiziaes, 15.5～25.5 parts of saponin of Radix Notoginseng leaf, 310～517 parts in Radix Glycyrrhizae;

(b) got 10～30 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 8～12 times of crude drug water gagings, reflux, extract, 1～3 hour filters filtrate for later use, medicinal residues add 8～12 times of crude drug water gagings, and reflux, extract, 1～3 hour filters, filtrate for later use, medicinal residues add 8～12 times of crude drug water gagings again, reflux, extract, 1～3 hour, filter, merge 3 times extracting solution, 60～80 ℃ are evaporated to 1g crude drug/ml, measure D ₆₀=1.06～1.09, add 95% ethanol and make and contain alcohol amount and reach 60%, standing over night filters, and filtrate recycling ethanol is at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 93～97% ethanol and make and contain the alcohol amount and reach 77～83%, standing over night filters, and filtrate is at D ₆₀=1.30～1.35 are evaporated to thick paste;

(c) in appropriate amount of auxiliary materials, add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract, fully mix, mixture stirs at 60～85 ℃ of heating and meltings, mixing time is 10～30 minutes, insulation is 1.1～3.5 millimeters at 60～85 ℃ of temperature following system, dropper bore, splashes in 0～18 ℃ the liquid paraffin, methyl-silicone oil, make drop pill, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.

12, the preparation method of Cure for insomnia medicine as claimed in claim 10 is characterized in that this method comprises the steps:

(a) take by weighing 1380 parts of Semen Ziziphi Spinosaes, 828 parts of Flos Albiziaes, 20.7 parts of saponin of Radix Notoginseng leaf, 414 parts in Radix Glycyrrhizae by proportioning raw materials;

(b) got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae add 10 times of crude drug water gagings, reflux, extract, 2 hours filters filtrate for later use, medicinal residues add 10 times of crude drug water gagings, and reflux, extract, 2 hours filters, filtrate for later use, medicinal residues add 10 times of crude drug water gagings again, reflux, extract, 2 hours, filter, merge 3 times extracting solution, 70 ℃ are evaporated to 1g crude drug/ml, measure D ₆₀=1.06～1.09, add 95% ethanol and make and contain alcohol amount and reach 60%, standing over night filters, filtrate recycling ethanol, at D ₆₀Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, standing over night filters, and filtrate decompression is concentrated into thick paste D ₆₀=1.30～1.35;

(c) add above-mentioned saponin of Radix Notoginseng leaf dry powder, Semen Ziziphi Spinosae, Flos Albiziae, Radix Glycyrrhizae extract in 2.5～5 times of amount adjuvants that are total extractum, fully mix, mixture is at 62～68 ℃ of heating and meltings, stir, mixing time is 10～30 minutes, and insulation is in following system of 62～68 ℃ of temperature, the dropper bore is 1.2～2.5 millimeters, splash in 0～8 ℃ the methyl-silicone oil, make drop pill, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.