CN101439105B - Chinese medicine granule containing spina date seed extract and preparation method thereof - Google Patents
Chinese medicine granule containing spina date seed extract and preparation method thereof Download PDFInfo
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- CN101439105B CN101439105B CN2007101503031A CN200710150303A CN101439105B CN 101439105 B CN101439105 B CN 101439105B CN 2007101503031 A CN2007101503031 A CN 2007101503031A CN 200710150303 A CN200710150303 A CN 200710150303A CN 101439105 B CN101439105 B CN 101439105B
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Abstract
The invention provides a traditional Chinese medicine granular preparation containing wild jujube extractive and a preparation method thereof. In the invention, traditional Chinese medicine spheroidized particles are prepared by traditional Chinese medicine extractive and carriers acceptable in pharmacy. The outline of the traditional Chinese medicine spheroidized particles takes sphere shape or round type shape. The density of the preparation is 0.6-1.3 g/ml. The spheroidized particles of the invention have low single dose, are convenient in use, can be served as intermediate products of capsules, and also can be used for developing a traditional Chinese medicine controlled release preparation.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof, be specifically related to a kind of Chinese medicinal granule that contains Semen Ziziphi Spinosae extract and preparation method thereof.
Background technology
Along with Chinese society's rapid economy development; The quickening of urbanization and aged tendency of population process; And the influence of factors such as competitive pressure, unemployment, rhythm of life variation, mental disorder causes various mental sickness such as insomnia, depression, neurosis, schizophrenia sharply to rise to the healthy harm of Chinese people " more and more outstanding and serious "; Because this disease sickness rate increases day by day, is called as " killer of new century ".Mental sickness more and more receives 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 like 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 possibly 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 treatments " restlessness of asrhenia type and insomnia greatly after being ill " such as selecting 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 adopts different Therapeutic Principle and square medicine respectively, no matter on etiology and pathogenesis according to the different syndromes of being insomnia; 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 ", explain 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,, the understanding of comparison system has been arranged all from theory into action.
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 at present commonly used also has in Tianwang Buxin Dan, ANSHEN BUXIN WAN, kidney-brain-nourishing tablet, Yening Tangjiang, Baijiang Tablets, taste the heart-yin oral liquid, mind-easing tonic bolus with arborvitate seed, Naolejing, ANSHEN BUNAO YE, nourishing blood to tranquillize the mind sheet, succinum Anshen Wan, three BAODAN, the holy pillow in hole brain invigorating liquid, allay excitement reinforcing the heart sheet, ANSHEN JIAONANG etc. in pellet, Xuefu ecchymosis eliminating pill, Radix Et Caulis Acanthopanacis Senticosi tablet, yangxue anshen pills, Pill of Magnetitum and Cinnabari, epilepsy medicine (Dianxianning) sheet, valiant fighter's pleasure, the safe and comfortable oral liquid of sleeping, sweet dreams oral liquid, BUZHONG YIQI WAN (sheet), Margarita powder, compound recipe Radix Schisandrae Bicoloris sheet, Qiyeshen an sheet, FUFANG ZAOREN JIAONANG, the pillow.Western medical treatment insomnia is main uses calm, hypnotic drug, and it mainly is divided into three major types: 1, benzodiazepine: this type drug main will have chlordiazepoxide, stabilizes, oxazepans, nitrodiazepam, tavor etc.2, barbiturates: this type medicine mainly contains phenobarbital, sodium phenobarbital etc.3, other miscellanies: like Paraldehyde, chloral hydrate, glutethimide, methaqualone, chlorpromazine, promethazine etc.Sleeping pill is one type the central nervous system is produced inhibitory action, can cause calm and hypnotic medicine, and its sedation and syngignoscism do not have 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; Mostly the dosage form of this type of medicine is that tablet, pill, oral liquid etc., drug effect effect are slow in addition, takes trouble.
The traditional preparation process method of Chinese medicinal granule is to adopt dry method or wet method to process the particulate material of certain particle size Chinese medicine or its extract, when supplying the patient to use with mixing in water for oral taking or swallow.The defective of at present common several kinds of granule preparation technologies and existence thereof: 1. conventional particles preparation technology; Because Chinese medical concrete viscosity is higher, there are problems such as particulate drug loading is low, outward appearance is not attractive in appearance, mouthfeel is poor, the easy moisture absorption mostly in the method for preparing of conventional particles.2. comparatively popular at present fluidized bed granulation technology is that drug powder and various adjuvant are packed in the container, is blown into the air-flow of preference temperature through sieve plate from the bed bottom; Make material mix homogeneously under fluidized state; Begin evenly to spray into binder liq then, powder begins the coalescence granulating, through spraying and drying repeatedly; When granular size meets the requirements, stop spraying, continue dry.This technology can be reduced to the adjuvant amount more than 50% by traditional 80%; The single dose of the grain products of preparation generally can be reduced to 3g to 5g by traditional 10g; But this technology can not thoroughly solve the problem of viscosity of Chinese medicine extract; Used adjuvant can not further reduce, and single agent dose is bigger, and patient's compliance is relatively poor; And use this kind method to be not suitable for processing solid preparations such as capsule; Adopting the granule of fluidized bed granulation technology at present commonly used preparation in addition is cellular, irregular shape; Moisture absorption is more common, and inconvenience is preserved; Particulate specific surface area is bigger, is not suitable for coating.3. also having Chinese medicine or plant amedica extract use fluidized-bed process manufacturing particle diameter is the research of the micropill technology of 700～1500 μ m; But this technology all is that medicine is processed dry powder; Water or other mixing material are as binding agent; Add medicine dry powder while spraying into liquid adhesive, process micropill.The micropill dissolve scattered time limit that at present adopts this explained hereafter is generally all at 40 minutes, and defective such as production process is comparatively complicated, cost is high, the influence factor is more (for example when air humidity is big, can not make), loss is bigger.4. also have to adopt in formulation art and extrude round or extrude the technology that spheronization is made micropill or spheroidal particle, this technology makes the goods support large usage quantity, and drug loading is general below 25%, and dissolve scattered time limit is more than 30 minutes.5. in formulation art, spray or side pressure spray process at the bottom of the fluid bed of employing are also arranged, make Western medicine micropill or spheroidal particle, be used for the exploitation of slow releasing preparation more, so development product generally has slow controlled release characteristics, do not possess the rapid release characteristic.
The rapid release of Chinese medicine and quick acting are importances of the modernization of Chinese medicine, adopt the Chinese medicine of manufacturing of the present invention or plant amedica granule to have fast instant diffusing characteristic.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicinal granule that contains Semen Ziziphi Spinosae extract.
Another object of the present invention is to provide a kind of method for preparing that contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract.
Drug selectivity sugariness of the present invention is put down GUIXIN, Liver Channel, has 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 from stem and leaf of Radix Notoginseng, purifying through scientific method, 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 animal quiet, lie 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, and the effect of utilizing 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 is to strengthen the effect that this prescription is calm, sleep peacefully.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract and realizes through following technical scheme:
Processed by Chinese medicine extract and pharmaceutically acceptable carrier, wherein Chinese medicine extract accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%; Described Chinese medicine extract is processed by following materials of weight proportions: 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.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, preferably realizes through following technical scheme:
Weight percentage by Chinese medicine extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein said Chinese medicine extract is processed by following materials of weight proportions: 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.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and the best realizes through following technical scheme:
Weight percentage by Chinese medicine extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%; Wherein Chinese medicine extract is processed by following materials of weight proportions: 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.
Chinese medicine extract described in the present invention; Can obtain according to method provided by the invention; Also can get like the preparation of methods such as decocting method, infusion process, percolation, circumfluence method, water extract-alcohol precipitation, alcohol extracting-water precipitating according to the conventional or commonly used method in present technique field; Can be extractum, also can be the effective site of further extraction separation acquisition or the compositions of effective site.
Among the present invention, said Chinese medicine extract prepares according to following method: wherein Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae 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, and reflux, extract, 0.5～5 hour filters; 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, below 40～90 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
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%, hold over night filters, and filtrate decompression is concentrated into thick paste; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed extract of the present invention.
Among the present invention, said Chinese medicine extract preferably prepares according to following method: wherein 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, and medicinal residues add 8～12 times of crude drug water gagings; Reflux, extract, 1～3 hour filters, filtrate for later use, and medicinal residues add 8～12 times of crude drug water gagings again; Reflux, extract, 1～3 hour filters, and merges 3 times extracting solution, P 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 hold over night filters, and filtrate recycling ethanol is at P
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%, hold over night filters, and filtrating is at P
60=1.30～1.35 are evaporated to thick paste; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed extract of the present invention.
Among the present invention, said Chinese medicine extract the best prepares according to following method: wherein 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, and medicinal residues add 10 times of crude drug water gagings; Reflux, extract, 2 hours filters, filtrate for later use, and medicinal residues add 10 times of crude drug water gagings again; Reflux, extract, 2 hours filters, and merges 3 times extracting solution, below 70 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
60Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste P
60=1.30～1.35; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed extract of the present invention.
Pharmaceutically acceptable carrier of the present invention can be any preparation Chinese medicinal granule pharmaceutically acceptable carrier commonly used or conventional, and for example: diluent (filler) includes but not limited to sucrose, dextrin, starch, lactose, mannitol, xylitol, chitosan, SHUANGQITANG, soluble starch, Pulvis Talci or water solublity dextrin etc.; Disintegrating agent includes but not limited to starch, sodium carboxymethyl cellulose (CMS-Na), microcrystalline Cellulose (MCC), micropowder silica gel, hydroxypropyl starch, soluble starch, water solublity dextrin; Inclusion agents includes but not limited to alpha-cyclodextrin (α-CD), beta-schardinger dextrin-(β-CD) and N-LOK modified starch etc.; Wetting agent (binding agent) includes but not limited to water, ethanol, polyvinylpyrrolidone (polyvidone), hydroxypropyl cellulose, Polyethylene Glycol above-mentioned adjuvant function such as diluent such as (PEG); Disintegrating agent, wetting agent by the function address, are viscosity modifier in this patent; Preferably microcrystalline cellulose (MCC), micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan; Pulvis Talci, the above-mentioned pharmaceutically acceptable carrier of polyvidone can use separately, also can unite use.Persons of ordinary skill in the art may appreciate that the following emerging pharmaceutically acceptable carrier that can be used for preparing Chinese medicinal granule,, also should be included in protection scope of the present invention if can realize the object of the invention.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and described pharmaceutically acceptable carrier preferably one or more in sucrose, dextrin, starch, lactose, mannitol, xylitol, chitosan, SHUANGQITANG, soluble starch, Pulvis Talci, water solublity dextrin sodium carboxymethyl cellulose (CMS-Na), microcrystalline Cellulose (MCC), micropowder silica gel, hydroxypropyl starch, ethanol, hydroxypropyl cellulose, Polyethylene Glycol, chitosan, polyvidone is united use.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and described pharmaceutically acceptable carrier is preferably: crystalline cellulose element, micropowder silica gel, Polyethylene Glycol, Pulvis Talci, chitosan, Pulvis Talci, polyvidone.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract; Described granule comprises master batch and is positioned at the shell on the master batch, and profile be spherical or type sphere, and bulk density is 0.6～1.3g/m; Dissolve scattered time limit is 0.4～5 minute, and active constituents of medicine is included among master batch and/or the shell.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and its particle diameter is 700～1500 μ m.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and said granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
The Chinese medicinal granule that the present invention contains Semen Ziziphi Spinosae extract adopts the fluidized bed granulation technology to granulate; Common fluidized bed granulation technology is directly packed into powdered substance and is granulated as bed material in the container of fluid bed; And the present invention forms with pharmaceutically acceptable preparing carriers, perhaps is prepared from pharmaceutically acceptable carrier and corresponding Chinese medicine extract dry powder.
The present invention contains the method for preparing of the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and step is following:
(1) preparation of extract of the present invention: Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae 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, and reflux, extract, 0.5～5 hour filters; 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, below 40～90 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
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%, hold over night filters, and filtrate decompression is concentrated into thick paste; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed extract of the present invention;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and Chinese medicine extract dry powder, and crushing screening obtains the satisfactory material of granularity; Ii. get the material of a part of step I, drop in spray of fluid bed side or the end spray pot, other gets it filled and learns acceptable carrier and/or Chinese medicine extract and add water and be mixed with slurry; Adopt spray of fluid bed side or end pressure spray process to spray into, and sift out granule, again parent nucleus is dropped in the pot as parent nucleus; Continue to spray and state slurry; The material of remaining step I is sprinkled into fine powder in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, filter out the satisfactory master batch of particle diameter;
(3) preparation of product: it is an amount of to get master batch, and acceptable carrier is an amount of, and active component of the present invention is an amount of; Above-mentioned acceptable carrier is added in the invention described above active component, and it is subsequent use as slurry to mix into suspension; Above-mentioned master batch is dropped in the fluid bed side spray pot, and above-mentioned slurry slowly sprays into, and all sprays into to slurry, processes spheroidal particle.
The present invention contains the method for preparing of the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and preferred steps is following:
(1) preparation of Chinese medicine extract of the present invention: 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; Filter, filtrate for later use, medicinal residues add 10 times of crude drug water gagings, reflux, extract, 2 hours; Filter, 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, below 70 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
60Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste P
60=1.30～1.35; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed extract of the present invention;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 1: 1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the active component of the present invention that accounts for the 15wt% of master batch weight after the dry weight; Add water and be mixed with slurry and spray into, and sift out particle diameter be 180～250 μ m granules as parent nucleus, again parent nucleus is dropped in the pot; Continue to spray and state slurry; In the dusting rifle, the dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is subsequent use;
(3) preparation of product: get master batch 350g; The active component of the present invention of 370g; With active component weight ratio of the present invention be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with active component weight ratio of the present invention: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in above-mentioned viscosity adjustment agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture; Add in the active component of the present invention; After the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
In the preparation process of active component of the present invention, the addition of Rhizoma Chuanxiong is 5～15% of the prescription total amount in the said step (a), and the powder particle diameter of Hirudo, Rhizoma Chuanxiong is 130～170 μ m; Decocting number of times in the said step (b) is 1～4 time, and amount of water is 6～10 times of dose, and the time is 1～3 hour; It is 1.0～1.5 that its water extract is concentrated into relative density, and alcoholic acid addition is to make its concentration reach 40～80%; After reclaiming ethanol, concentrated extract to relative density is 1.0～1.5; Alcohol reflux is 1～4 time in the said step (c), and alcohol adding amount is 6～10 times of dose, and the time is 1～3 hour, and behind the recovery ethanol, concentrated extract to relative density is 1.0～1.5.
The present invention contains in the method for preparing of Chinese medicinal granule of Semen Ziziphi Spinosae extract, and the temperature of charge of the spheroidal particle that can said method be obtained is controlled at 37～45 ℃; Transparent coating material water is made into the coating solution of 7.5% (g/ml) again, according to the amount of theory weightening finish 3wt% coating solution is sprayed into coating, process spheroidal particle, its bulk density is 0.76g/ml, and dissolve scattered time limit is 25～180 seconds.
The present invention contains in the method for preparing of Chinese medicinal granule of Semen Ziziphi Spinosae extract, No. 2 capsules of spheroidal particle fill that can said method be obtained, and the 250mg/ grain is processed 10000 of capsules.
" setting of dosage form in the Chinese pharmacopoeia, and in order to distinguish different with technology such as micropill, microcapsules in conjunction with the characteristic of present technique preparing product, was named above-mentioned granule and is spheroidized particle according to version in 2005.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, outside it coating can also be arranged, and the weight of coating materials accounts for the 2-5% of granule gross weight.During the spheroidized particle coating, obviously low (plain particles coating, coating materials consumption are 20-30% to the more common granule coating of the consumption of coating materials, and spheroidized particle coating materials consumption then can be reduced to 2-5% with the adjuvant amount.As required; Coating can be common film coating, also can be enteric film coating, slow controlled release coat etc., and coating materials can be the commonly used or conventional coating materials in any this area; Select according to different needs, the coating process can be carried out according to the conventional method in this area.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, directly uses except can be used as common granule, can also be as intermediate; Be prepared into dosage forms such as capsule; As granule use etc., can be prepared into sustained-release preparation in addition, positioning release medicine preparation etc.
The present invention contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract, and preferred said granule is processed conventional capsule agent or sustained-release preparation.
Spheroidized particle of the present invention has the following advantages:
1. the consumption of adjuvant is few, therefore causes single dose little, and the general each dose of patient is that 0.1～4g gets final product, and can reduce the fear that the patient takes medicine and produced heavy dose.
2. outward appearance is good, granule of the present invention spherical in shape or type spherical, smooth surface rounding, the control of suitable product design quality.
3. physical characteristic is good, prepares in the process at spheroidal particle, and mobility of particle is good, causes that particle size distribution is regular, the fine and close anti-extruding of quality, and wear-resistant, density is big, and (bulk density is 0.6～1.3g/ml), specific surface area is little (has only 0.01～0.03m
2/ g).
4. dissolve scattered time limit is short, and the spheroidal particle dissolve scattered time limit of the present invention that adopts this type of prescription to make is short, is generally 0.4～5 minute.
5. granularity test: according to 2000 editions pharmacopeia regulations, get granule 5 bags of (bottle) or multiple dose packing granule 1 bags (bottle) of single dose packing, claim to decide weight, put in the medicine sieve and sieve.When sieving, will sieve and keep level, about come and go and sieved gently 3 minutes.Can not and can must not cross 8.0% through a sieve through the granule and the powder summation of No. four sieves.Granule of the present invention can not and can meet the pharmacopeia regulation through the granule and the powder summation of No. four sieves through a sieve, and its numerical value is no more than 5.5%.
6. melting test: according to 2000 editions pharmacopeia regulations, get medicinal granule test sample 10g of the present invention, add 20 times of hot water, stirred 5 minutes, observe immediately.Soluble granule is answered off-bottom.
These characteristics can improve patient's the row of complying with, and makes the application of packaging technique become possibility, thereby has solved the moisture absorption (critical wettability is promoted to 85% by 60% of plain particles) of Chinese medicine, problem such as stable; In addition, spheroidized particle of the present invention uses except can be used as common granule, can also be as intermediate or granule, and fill becomes dosage forms such as capsule, can be prepared into sustained-release preparation in addition, positioning release medicine preparation etc.
The specific embodiment
Below in conjunction with specific embodiment the present invention is further described, following this embodiment only is used to the present invention is described and the present invention is not limited.
Embodiment 1
The preparation of active component of the present invention: (a): it is subsequent use to get Semen Ziziphi Spinosae 1380g, Flos Albiziae 828g, saponin of Radix Notoginseng leaf 20.7g, Radix Glycyrrhizae 414g; (b): get Semen Ziziphi Spinosae coarse powder (cross 20 mesh sieves), Flos Albiziae, Radix Glycyrrhizae and 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, be evaporated to 1g crude drug/ml (P below 70 ℃
60=1.06～1.09), add 95% ethanol and make and contain alcohol amount and reach 60%, hold over night filters, and filtrate recycling ethanol is to 3g crude drug/ml (P
60=1.12～1.14), add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste (P
60=1.30～1.35); (c) get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, heating in water bath makes dissolving, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the weight ratio of getting dextrin and starch is that 1: 1 mixture is crossed 200 mesh sieves; Wherein 65% as in the bed material input fluid bed side spray pot; Other gets starch and adds water and be mixed with starch slurry (15%) and spray into as slurry, and sifts out granule (particle diameter is 180-250 μ) as parent nucleus, parent nucleus is dropped in the pot again; Continue the spray starch slurry; 35% the dextrin of remainder and the fine powder of starch are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 450 μ-600 μ to filter out particle diameter.
The preparation of product: get master batch 350g, microcrystalline Cellulose (200 order) 15g, polyethylene glycol 6000 (heating and melting)
250G, active component 320g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and adding water, to mix into solid content be 30% binding agent; Master batch is dropped in the fluid bed side spray pot; Slurry is slowly sprayed into; Constantly be dried to simultaneously slurry and all spray into and process spheroidal particle, temperature of charge is controlled at 55 degrees centigrade, and coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution; Amount according to theory weightening finish 3% sprays into coating with coating solution, processes spheroidal particle.
Embodiment 2
The preparation of active component of the present invention: (a): it is subsequent use to get Semen Ziziphi Spinosae 690g, Flos Albiziae 500g, saponin of Radix Notoginseng leaf 12.5g, Radix Glycyrrhizae 220g; (b): get Semen Ziziphi Spinosae coarse powder (cross 20 mesh sieves), Flos Albiziae, Radix Glycyrrhizae and 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 hours filters; Filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, reflux, extract, 1 hour; Filter, merge 3 times extracting solution, be evaporated to 1g crude drug/ml (P below 70 degrees centigrade
60=1.06～1.09), add 95% ethanol and make and contain alcohol amount and reach 60%, hold over night filters, and filtrate recycling ethanol is to 3g crude drug/ml (P
60=1.12～1.14), add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste (P
60=1.30～1.35).Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, heating in water bath makes dissolving, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting micropowder silica gel and chitosan weight ratio and being 1: 1 is crossed 200 mesh sieves; Wherein 65% as in the bed material input fluid bed side spray pot; Other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and sift out particle diameter be 120-180 μ granule as parent nucleus, again parent nucleus is dropped in the pot; Continue the spray starch slurry; 35% the micropowder silica gel of remainder and the fine powder of chitosan are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 330g, microcrystalline Cellulose (200 order) 205g, micropowder silica gel 6g, active component 420g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and it is subsequent use as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot; Slurry is slowly sprayed into, constantly be dried to simultaneously slurry and all spray into and process spheroidal particle, coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution; Amount according to theory weightening finish 3% sprays into coating with coating solution, processes spheroidal particle.Particulate bulk density 0.93g/ml is with No. 00 capsule of the spheroidal particle fill that obtains.
Embodiment 3
The preparation of active component of the present invention: it is subsequent use (a) to get Semen Ziziphi Spinosae 2070g, Flos Albiziae 1200g, saponin of Radix Notoginseng leaf 15g, Radix Glycyrrhizae 500g; (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 10 times of crude drug water gagings again, reflux, extract, 2 hours; Filter, merge 3 times extracting solution, below 80 ℃, P
60=1.06～1.09 are evaporated to 1g crude drug/ml, add 99% ethanol and make and contain alcohol amount and reach 70%, and hold over night filters, filtrate recycling ethanol, at P
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%, hold over night filters, and filtrate decompression is concentrated into thick paste; (c) get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 1: 1 is crossed 200 mesh sieves; Wherein 65% as in the bed material input fluid bed side spray pot; Other gets starch, extract (account for after giving money as a gift master batch weight 15%) and adds water and be mixed with slurry and spray into, and sifts out granule (particle diameter is 180～250 μ) as parent nucleus, parent nucleus is dropped in the pot again; Continue the spray starch slurry; 35% the dextrin of remainder and the fine powder of starch are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 300 μ～400 μ to filter out particle diameter.
The preparation of product: get master batch 405g, microcrystalline Cellulose (200 order) 55g, polyethylene glycol 6000 (heating and melting)
350G, active component 360g of the present invention; Microcrystalline Cellulose and micropowder silica gel are added in the active component of the present invention, and adding water, to mix into solid content be 30% binding agent; Master batch is dropped in the fluid bed side spray pot; Slurry is slowly sprayed into, constantly be dried to simultaneously slurry and all spray into and process spheroidal particle, temperature of charge is controlled at 55 degrees centigrade; Coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution; Amount according to theory weightening finish 30% sprays into coating with coating solution, processes spheroidal particle, and bulk density is 0.76g/ml; With No. 2 capsules of the spheroidal particle fill that obtains, every dress 0.125g.
Embodiment 4
The preparation of active component of the present invention: it is subsequent use (a) to get Semen Ziziphi Spinosae 1035g, Flos Albiziae 621g, saponin of Radix Notoginseng leaf 15.5g, Radix Glycyrrhizae 310g; (b) got 30 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 12 times of crude drug water gagings, reflux, extract, 3 hours; Filter, filtrate for later use, medicinal residues add 8 times of crude drug water gagings, reflux, extract, 3 hours; Filter, filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, reflux, extract, 1 hour; Filter, merge 3 times extracting solution, P 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 hold over night filters, and filtrate recycling ethanol is at P
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%, hold over night filters, and filtrating is at P
60=1.30～1.35 are evaporated to thick paste; (c) get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and being 1: 1 is crossed 200 mesh sieves; Wherein 65% as in the bed material input fluid bed side spray pot; Other gets PVP K30 and adds water and be mixed with bonding agent (5%) and spray into as slurry, and sift out particle diameter be 180～250 μ granules as parent nucleus, again parent nucleus is dropped in the pot; Continue the spray starch slurry; 35% the dextrin of remainder and the fine powder of microcrystalline Cellulose are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 300 μ～400 μ to filter out particle diameter.
The preparation of product: get master batch 1000g, add invention active component 750g, 5% polyvidone solution, adding water, to mix into solid content be that 30% suspension is subsequent use as slurry; Master batch is dropped in the fluid bed side spray pot; Slurry is slowly sprayed into, constantly be dried to simultaneously slurry and all spray into and process spheroidal particle, coating material OPAGLOS 2 waters that reuse is transparent are made into 7.5% coating solution; Amount according to theory weightening finish 3% sprays into coating with coating solution, processes spheroidal particle.
Embodiment 5
The preparation of active component of the present invention: it is subsequent use (a) to get Semen Ziziphi Spinosae 1725g, Flos Albiziae 1035g, saponin of Radix Notoginseng leaf 25.5g, Radix Glycyrrhizae 310g; (b) got 10 mesh sieve Semen Ziziphi Spinosae coarse powder, Flos Albiziae, Radix Glycyrrhizae add 11 times of crude drug water gagings, reflux, extract, 2.5 hours; Filter, filtrate for later use, medicinal residues add 9 times of crude drug water gagings, reflux, extract, 1.5 hours; Filter, filtrate for later use, medicinal residues add 8 times of crude drug water gagings again, reflux, extract, 1 hour; Filter, merge 3 times extracting solution, P 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 hold over night filters, and filtrate recycling ethanol is at P
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%, hold over night filters, and filtrating is at P
60=1.30～1.35 are evaporated to thick paste; (c) get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting dextrin and microcrystalline Cellulose weight ratio and being 2: 1 is crossed 100 mesh sieves; Wherein 75% as in the bed material input fluid bed side spray pot; Other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and sift out particle diameter be 100-200 μ granule as parent nucleus, again parent nucleus is dropped in the pot; Continue the spray starch slurry; 35% the dextrin of remainder and the fine powder of microcrystalline Cellulose are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 800g, microcrystalline Cellulose 190g, micropowder silica gel 35g, invention active component 450g; Microcrystalline Cellulose and micropowder silica gel are added in the invention active component, and it is subsequent use as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 6
The preparation of active component of the present invention: it is subsequent use (a) to get Semen Ziziphi Spinosae 140g, Flos Albiziae 750g, saponin of Radix Notoginseng leaf 20.7g, Radix Glycyrrhizae 300g; (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; Filter, filtrate for later use, medicinal residues add 10 times of crude drug water gagings, reflux, extract, 2 hours; Filter, 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, below 70 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
60Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste P
60=1.30～1.35; (c) get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously, preparation cost invention active component.
The preparation of master batch: the mixture of getting micropowder silica gel and Pulvis Talci weight ratio and being 1: 1 is crossed 200 mesh sieves; Wherein 50% as in the bed material input fluid bed side spray pot; Other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and sift out particle diameter be 120-180 μ granule as parent nucleus, again parent nucleus is dropped in the pot; Continue the spray starch slurry; 35% micropowder silica gel and talcous fine powder of remainder is sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 300g, microcrystalline Cellulose (200 order) 250g, micropowder silica gel 14g, invention active component 300g; Microcrystalline Cellulose and micropowder silica gel are added in the invention active component, and it is subsequent use as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 7
It is an amount of to get the active component of the present invention that obtains according to embodiment 1 method;
The preparation of master batch: taking polyethylene glycol and chitosan weight ratio are that 1: 1 mixture is crossed 200 mesh sieves; Wherein 65% as in the bed material input fluid bed side spray pot; Other gets PVP K30 and adds water, extract, is mixed with bonding agent-spray into as slurry, and sift out particle diameter be 120-180 μ granule as parent nucleus, again parent nucleus is dropped in the pot; Continue the spray starch slurry; 35% the Polyethylene Glycol of remainder and the fine powder of chitosan are sprinkled in the dusting rifle simultaneously, the particle diameter of parent nucleus is grown up, it is subsequent use at the master batch of 200 μ-300 μ to filter out particle diameter.
The preparation of product: get master batch 700g, microcrystalline Cellulose (200 order) 300g, micropowder silica gel 20g, invention active component 430g; Microcrystalline Cellulose and micropowder silica gel are added in the invention active component, and it is subsequent use as slurry to mix into uniform suspension; Master batch is dropped in the fluid bed side spray pot, slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 8:
1, it is an amount of to get the active component of the present invention that obtains according to embodiment 2 methods;
2, the preparation of master batch: get dextrin and starch (1: 1) mixture and cross 200 mesh sieves; Wherein 65wt% drops in the fluid bed side spray pot, other get starch add water be mixed with starch slurry (15%, g/ml) spray into as slurry; And sift out granule (particle diameter is 180～250 μ m) as parent nucleus; Again parent nucleus is dropped in the pot, continue to spray and state starch slurry, remaining 35% the dextrin and the fine powder of starch (1: 1) mixture are sprinkled in the dusting rifle simultaneously; The particle diameter of parent nucleus is grown up, and it is subsequent use at the master batch of 450～600 μ m to filter out particle diameter.
3, the selection of viscosity adjustment agent
A. get the foregoing invention active component, be diluted to the diluent that viscosity is 6.0～9.8MpaS with the alcoholic solution of 60% (ml/ml).
B. get 1 above-mentioned diluent, drop on the microscope slide, hang, solid cicatrix surface, liquid evaporation back does not have complete film, and viscosity is less, is prone to scrape with powdery, and it is serious to play powder.
C. the viscosity according to cicatrix among the b is little, film property is poor, intensity is little, be prone to characteristics such as powder; Select viscosity adjustment agent; Experiment shows can select HPMC: PVP-K30 (2: 5) mixture to adjust agent as viscosity, and also can select polyethylene glycol 6000 is viscosity adjustment agent.
D. selection and invention active component weight ratio are 7: 25 HPMC: PVP-K30 (2: 5) mixture is viscosity adjustment agent; Perhaps selection and invention active component weight ratio are that 18: 25 polyethylene glycol 6000 is viscosity adjustment agent, are increased to 16MPaS to material viscosity by 9.0MPaS.
4, the preparation of spheroidal particle of the present invention
A. get master batch 450g, with invention active component weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC: PVP-K30 (2: 5) mixture, the invention active component of 340g with invention active component weight ratio;
B. use dehydrated alcohol with a kind of solution that is formulated as concentration as 5wt% in the above-mentioned viscosity adjustment agent, add in the invention active component, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry;
C. master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle; Temperature of charge is controlled at 37～45 ℃; Again transparent coating material water is made into the coating solution of 7.5% (g/ml), coating solution is sprayed into coating, process spheroidal particle according to the amount of theory weightening finish 3wt%; Its bulk density is 0.76g/ml, and dissolve scattered time limit is 30 seconds.
With No. 2 capsules of the spheroidal particle fill that obtains among the step c, the 250mg/ grain is processed capsule.
Embodiment 9
1, it is an amount of to get the active component of the present invention that obtains according to embodiment 3 methods;
2, the preparation of master batch: get xylitol and carboxymethyl starch sodium (1: 1) mixture and cross 200 mesh sieves; Wherein 60wt% drops in the fluid bed side spray pot, and other gets 10wt% xylitol and carboxymethyl starch sodium (1: 1) mixture and invents active component (after amounting to dry weight, accounting for the 15wt% of master batch weight) and add water and be mixed with slurry and spray into; And sift out granule (particle diameter is 180～250 μ m) as parent nucleus; Again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the xylitol of remaining 30wt% and the fine powder of carboxymethyl starch sodium (1: 1) mixture are sprinkled into simultaneously; The particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 280～450 μ m is subsequent use.
3, the preparation of product: get master batch 450g; The invention active component of 440g, with invention active component weight ratio be 18: 25 polyethylene glycol 6000, uses dehydrated alcohol that above-mentioned viscosity is adjusted the agent polyethylene glycol 6000 and is formulated as the solution of concentration as 15wt%; Add in the invention active component; After the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 10
1, it is an amount of to get the active component of the present invention that obtains according to embodiment 4 methods;
2, the preparation of master batch: get lactose and hydroxypropyl starch (1: 1) mixture and cross 200 mesh sieves; Wherein 60wt% drops in the fluid bed side spray pot, and other gets 10wt% lactose and hydroxypropyl starch (1: 1) mixture and invents active component (after amounting to dry weight, accounting for the 15wt% of master batch weight) and add water and be mixed with slurry and spray into; And sift out granule (particle diameter is 180～250 μ m) as parent nucleus; Again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the lactose of remaining 30wt% and the fine powder of hydroxypropyl starch (1: 1) mixture are sprinkled into simultaneously; The particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 180～250 μ m is subsequent use.
3, the preparation of product: get master batch 850g, the invention active component of 500g, with invention active component weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol that above-mentioned viscosity adjustment agent HPMC is formulated as the solution of concentration as 15wt% with the PVP-K30 mixture, add and invent in the active component, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 20wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 11
1, it is an amount of to get the active component of the present invention that obtains according to embodiment 5 methods;
2, the preparation of master batch: get dextrin and mannitol (3: 1) mixture and cross 200 mesh sieves; Wherein 64wt% drops in the fluid bed side spray pot, and other gets 16wt% dextrin and mannitol mixture and invents active component (after amounting to dry weight, accounting for the 10wt% of master batch weight) and add water and be mixed with slurry and spray into; And sift out granule (particle diameter is 180～250 μ m) as parent nucleus; Again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the dextrin of remaining 20wt% and the fine powder of mannitol mixture are sprinkled into simultaneously; The particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 450～600 μ m is subsequent use.
3, the preparation of product: get master batch 500g, the invention active component of 500g, with invention active component weight ratio be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol that above-mentioned viscosity adjustment agent HPMC is formulated as the solution of concentration as 15wt% with the PVP-K30 mixture, add and invent in the active component, after the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 20wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 12
1, it is an amount of to get the active component of the present invention that obtains according to embodiment 6 methods;
2, the preparation of master batch: get dextrin and mannitol (2: 1) mixture and cross 200 mesh sieves; Wherein 65wt% drops in the fluid bed side spray pot, and other gets 25wt% dextrin and mannitol mixture and invents active component (after amounting to dry weight, accounting for the 10wt% of master batch weight) and add water and be mixed with slurry and spray into; And sift out granule (particle diameter is 180～250 μ m) as parent nucleus; Again parent nucleus is dropped in the pot, continue to spray and state slurry, in the dusting rifle, the dextrin of remaining 10wt% and the fine powder of mannitol mixture are sprinkled into simultaneously; The particle diameter of parent nucleus is grown up, and the master batch that filters out particle diameter and be 450～600 μ m is subsequent use.
3, the preparation of product: get master batch 450g; The invention active component of 800g, with invention active component weight ratio be 18: 25 polyethylene glycol 6000, uses dehydrated alcohol that above-mentioned viscosity is adjusted the agent polyethylene glycol 6000 and is formulated as the solution of concentration as 15wt%; Add in the invention active component; After the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Embodiment 13
(1) it is an amount of to get the active component of the present invention that obtains according to embodiment 1 method;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 1: 1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the invention active component that accounts for the 15wt% of master batch weight after the dry weight; Add water and be mixed with slurry and spray into, and sift out particle diameter be 180～250 μ m granules as parent nucleus, again parent nucleus is dropped in the pot; Continue to spray and state slurry; In the dusting rifle, the dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is subsequent use;
(3) preparation of product: get master batch 350g; The invention active component of 370g; With invention active component weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with invention active component weight ratio: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in above-mentioned viscosity adjustment agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture; Add in the invention active component; After the mixing, adding 60% (ml/ml) ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
Claims (6)
1. Chinese medicinal granule that contains Semen Ziziphi Spinosae extract; Described granule comprises master batch and is positioned at the shell on the master batch; Profile is spherical or type sphere, and bulk density is 0.6～1.3g/ml, and dissolve scattered time limit is 0.4～5 minute; Active constituents of medicine is included among master batch and/or the shell, and its preparation method is following:
(1) preparation of active component: described active component is processed by following materials of weight proportions: 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; Got the Semen Ziziphi Spinosae coarse powder of 20 mesh sieves, Flos Albiziae, Radix Glycyrrhizae 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, 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, and merges 3 times extracting solution, below 70 ℃, P60=1.06～1.09 are evaporated to 1g crude drug/ml; Add 95% ethanol and make and contain alcohol amount and reach 60%, hold over night filters, and filtrate recycling ethanol, time is concentrated into 3g crude drug/ml in P60=1.12～1.14; Add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste P60=1.30～1.35; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed active component;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 1: 1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the active component of the present invention that accounts for the 15wt% of master batch weight after the dry weight; Add water and be mixed with slurry and spray into, and sift out particle diameter be 180～250 μ m granules as parent nucleus, again parent nucleus is dropped in the pot; Continue to spray and state slurry; In the dusting rifle, the dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is subsequent use;
(3) preparation of product: get master batch 350g; The active component of 370g; With the active component weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the active component weight ratio: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in above-mentioned viscosity adjustment agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture; Add in the active component; After the mixing, adding 60%ml/ml ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
2. the Chinese medicinal granule that contains Semen Ziziphi Spinosae extract according to claim 1 is characterized in that described active component processed by following materials of weight proportions: 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.
3. like the said Chinese medicinal granule that contains Semen Ziziphi Spinosae extract of claim 2, it is characterized in that described active component processed by following materials of weight proportions: 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.
4. the Chinese medicinal granule that contains Semen Ziziphi Spinosae extract according to claim 1 is characterized in that its particle diameter is 700～1500 μ m.
5. the Chinese medicinal granule that contains Semen Ziziphi Spinosae extract according to claim 1 is characterized in that said granule also contains coating, and the weight of coating materials accounts for 2～5wt% of granule gross weight.
6. the said according to claim 1 method for preparing that contains the Chinese medicinal granule of Semen Ziziphi Spinosae extract is characterized in that step is following:
(1) preparation of active component of the present invention: 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; Filter, filtrate for later use, medicinal residues add 10 times of crude drug water gagings, reflux, extract, 2 hours; Filter, 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, below 70 ℃, P
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 hold over night filters, filtrate recycling ethanol, at P
60Be concentrated into 3g crude drug/ml=1.12～1.14 times, add 95% ethanol and make and contain alcohol amount and reach 80%, hold over night filters, and filtrate decompression is concentrated into thick paste P
60=1.30～1.35; Get saponin of Radix Notoginseng leaf dry powder and add in Semen Ziziphi Spinosae, Flos Albiziae, the Radix Glycyrrhizae extract, mix homogeneously is processed active component;
(2) preparation of master batch: the mixture of getting dextrin and starch weight ratio and being 1: 1 is crossed 200 mesh sieves, and wherein 60-65wt% drops in the fluid bed side spray pot as bed material; 10-15wt% dextrin and starch mixture, amount to the active component of the present invention that accounts for the 15wt% of master batch weight after the dry weight; Add water and be mixed with slurry and spray into, and sift out particle diameter be 180～250 μ m granules as parent nucleus, again parent nucleus is dropped in the pot; Continue to spray and state slurry; In the dusting rifle, the dextrin of surplus and the fine powder of starch mixture are sprinkled into simultaneously, the particle diameter of parent nucleus is grown up, the master batch that filters out particle diameter and be 450～600 μ m is subsequent use;
(3) preparation of product: get master batch 350g; The active component of 370g; With the active component weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with active component weight ratio of the present invention: the PVP-K30 weight ratio is 2: 5; Use dehydrated alcohol with a kind of solution that is formulated as concentration as 15wt% in above-mentioned viscosity adjustment agent polyethylene glycol 6000 or HPMC and the PVP-K30 mixture; Add in the active component; After the mixing, adding 60%ml/ml ethanol, to transfer to solids content be 19wt%, as slurry; Master batch is dropped in the fluid bed side spray pot, above-mentioned slurry is slowly sprayed into, constantly be dried to slurry simultaneously and all spray into and process spheroidal particle.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101503031A CN101439105B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing spina date seed extract and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2007101503031A CN101439105B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing spina date seed extract and preparation method thereof |
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| CN101439105A CN101439105A (en) | 2009-05-27 |
| CN101439105B true CN101439105B (en) | 2012-04-18 |
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| CN110051713B (en) * | 2019-05-15 | 2021-10-01 | 青海普兰特药业有限公司 | Antidiarrheal semen formula particle, preparation method and detection method |
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