CN101439107B - Chinese medicine granule containing haw thorn extract and preparation method thereof - Google Patents
Chinese medicine granule containing haw thorn extract and preparation method thereof Download PDFInfo
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- Medicinal Preparation (AREA)
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Abstract
The invention provides a traditional Chinese medicine granular preparation containing hawthorn extractive and a preparation method thereof. In the invention, traditional Chinese medicine spheroidized particles are prepared by hawthorn 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 Fructus Crataegi extract and preparation method thereof.
Background technology
Background technology
First of each big disease of cardiovascular and cerebrovascular disease row, the serious harm human body is healthy, and the sequela that is caused is also brought very big misery to patient and family members, becomes the social problem of a worth extensive concern.Coronary flow is an important indicator of estimating the control myocardial ischemia drug, and external coronary flow is measured can observe the influence of medicine to coronary resistance.Anoxia enduring is that medicine improves body tissue (particularly cerebral tissue and heart tissue) hypoxia-bearing capability, improves one of important mechanisms of energy metabolism.Countries in the world medicine worker constantly studies, develops the medicine of cardiovascular and cerebrovascular disease, and the cardiovascular and cerebrovascular disease patient can effectively be treated.The medicine that is used to treat cardiovascular disease at present is more, and it is real that the Fructus Crataegi Tang materia medica is called red pawl, and ancient prescription is seldom used, from the beginning merit of Fructus Crataegi of Zhu Dan small stream, satisfies and is key medicine.Fructus Crataegi property is sour, sweet, tepor, returns spleen, stomach, Liver Channel, has promoting digestion and removing stagnation, promoting blood circulation to remove blood stasis.The at present clinical food stagnation that is mainly used in is stagnated, normal and compatibility application such as Fructus Hordei Germinatus, six songs; Also be used for postpartum stagnation stomachache, lochiorrhea, compatibilities such as normal and Radix Angelicae Sinensis, Rhizoma Chuanxiong, Herba Leonuri; Also be used for the treatment of hypertension, coronary heart disease, hyperlipidemia in recent years.Modern pharmacology evidence, Fructus Crataegi have the increase myocardial contraction, increase cardiac output, decreased heart rate, and the coronary artery dilator blood vessel reduces myocardial oxygen consumption, and can bring high blood pressure down and blood fat.What play a major role in the Fructus Crataegi is Fructus Crataegi total flavones.Fructus Crataegi total flavones be used to treat cardiovascular and cerebrovascular disease many with the use of drug for invigorating blood circulation and eliminating stasis compatibility, use separately less, Fructus Crataegi total flavones and which kind of adjuvant is used and Fructus Crataegi total flavones and adjuvant between the proportioning of the best be the key that influences curative effect of medication.
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 Fructus Crataegi 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 Fructus Crataegi extract.
Another object of the present invention is to provide a kind of method for preparing that contains the Chinese medicinal granule of Fructus Crataegi extract.
The May Rosaceae Crataegus is the conventional Chinese medicine material, and the sweet tepor of its nature and flavor acid can appetite-stimulating indigestion-relieving, removing food stagnancyization stagnates, activating blood circulation to dissipate blood stasis, convergence dysentery relieving.Be widely used in common disease such as treatment dyspepsia, hyperlipidemia and coronary heart disease etc., its contained flavones ingredient of bibliographical information has the effect of blood pressure lowering, blood fat reducing, antioxidation, dilating coronary blood vessel, coronary blood flow increasing.
Fructus Crataegi total flavones extracts from Rosaceae Crataegus plant Folium Crataegi.Be sundown or pale brown toner end, special aroma arranged, odorless, bitter in the mouth, soluble in water and ethanol.Main active is vitexin rhamnopyranoside and vitexin glycoside etc.Has anticoagulant, coronary artery dilator; Improve blood supply of cardiac muscle, reduce myocardial oxygen consumption, ischemic heart desease is produced the significant protection effect, have blood fat reducing, the effect of blood pressure lowering.Be applicable to coronary heart disease, coronary insufficiency, angina pectoris and treatment cardiovascular disease etc.The present invention utilizes this effect of the Radix Astragali just, through a large amount of tests, processes pharmaceutical composition of the present invention.
Fructus Crataegi extract can adopt at present common method for distilling to extract its effective ingredient in the bright medicine of this law, but in order to make Fructus Crataegi bring into play better drug effect, preferably adopt following technology to extract to raw material, but this can not limit protection scope of the present invention.
Get Fructus Crataegi, add ethanol extraction 3 times, merge extractive liquid,, hold over night is filtered; Filtrating concentrates, and reclaims ethanol, and concentrated solution is crossed macroporous adsorbent resin, adds the suitable quantity of water eluting, the reuse ethanol elution; Merge concentrated solution, cross and gather fine amine, washing, reuse ethanol is washed, and concentrates to obtain Fructus Crataegi extract.
The method for distilling of Fructus Crataegi extract is in the preferred medicine of the present invention: get Fructus Crataegi, extract altogether 3 times, add 70% the ethanol extraction 0.5 hour of 7 times of amounts for the first time, add 70% the ethanol extraction 0.5 hour of 6 times of amounts for the second time; Add 70% the ethanol extraction 0.5 hour of 6 times of amounts for the third time, hold over night is filtered; Filtrating concentrates, and reclaims ethanol, and concentrated solution is crossed macroporous adsorbent resin; Add the suitable quantity of water eluting, reuse 30% ethanol elution merges concentrated solution, crosses and gather fine amine; Washing, reuse 50% ethanol is washed, and concentrates to obtain Fructus Crataegi extract.
The present invention contains the Chinese medicinal granule of Fructus Crataegi extract and realizes through following technical scheme:
Processed by Fructus Crataegi extract and pharmaceutically acceptable carrier, wherein Fructus Crataegi extract accounts for 40～90% of percentage by weight, and pharmaceutically acceptable vehicle weight percentage composition is 10～60%.
The present invention contains the Chinese medicinal granule of Fructus Crataegi extract, preferably realizes through following technical scheme:
Weight percentage by Fructus Crataegi extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
The present invention contains the Chinese medicinal granule of Fructus Crataegi extract, and the best realizes through following technical scheme:
Weight percentage by Fructus Crataegi extract is 70～80%, and pharmaceutically acceptable vehicle weight percentage composition is 20～30%.
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 Fructus Crataegi 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 Fructus Crataegi 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 Fructus Crataegi 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/ml; 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 Fructus Crataegi extract, and its particle diameter is 700～1500 μ m.
The present invention contains the Chinese medicinal granule of Fructus Crataegi 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 Fructus Crataegi 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 Fructus Crataegi extract dry powder.
The present invention contains the method for preparing of the Chinese medicinal granule of Fructus Crataegi extract, and step is following:
(1) it is an amount of to get Fructus Crataegi extract;
(2) preparation of master batch: i. gets an amount of pharmaceutically acceptable carrier, the perhaps mixture of itself and Fructus Crataegi 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 Fructus Crataegi 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 Fructus Crataegi extract is an amount of; Above-mentioned acceptable carrier is added in the above-mentioned Fructus Crataegi extract, 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 Fructus Crataegi extract, and preferred steps is following:
(1) it is an amount of to get Fructus Crataegi extract;
(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 Fructus Crataegi extract 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 450g; The Fructus Crataegi extract of 300g; With the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the Fructus Crataegi extract 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 Fructus Crataegi extract; 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.
The present invention contains in the method for preparing of Chinese medicinal granule of Fructus Crataegi 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 Fructus Crataegi extract, No. 2 capsules of spheroidal particle fill that can said method be obtained, and the 250mg/ grain is processed capsule.
" 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 Fructus Crataegi 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 Fructus Crataegi 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 Fructus Crataegi 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
Get Fructus Crataegi, extract altogether 3 times, add for the first time 70% the ethanol extraction 0.5 hour of 7 times of amounts, add 70% the ethanol extraction 0.5 hour of 6 times of amounts for the second time; Add 70% the ethanol extraction 0.5 hour of 6 times of amounts for the third time, hold over night is filtered, and filtrating concentrates; Reclaim ethanol, concentrated solution is crossed macroporous adsorbent resin, add the suitable quantity of water eluting, reuse 30% ethanol elution; Merge concentrated solution, cross and gather fine amine, washing, reuse 50% ethanol is washed, and concentrates to obtain Fructus Crataegi extract.
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 450g, microcrystalline Cellulose (200 order) 50g, polyethylene glycol 6000 (heating and melting)
500G, Fructus Crataegi extract 320g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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
It is an amount of to get the Fructus Crataegi extract that obtains according to embodiment 1 method;
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 300g, microcrystalline Cellulose (200 order) 250g, micropowder silica gel 14g, Fructus Crataegi extract 200g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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.
Embodiment 3
It is an amount of to get the Fructus Crataegi extract that obtains according to embodiment 1 method;
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 450g, microcrystalline Cellulose (200 order) 50g, polyethylene glycol 6000 (heating and melting)
500G, Fructus Crataegi extract 1000g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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 3% 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 processes 10000 of capsules.
Embodiment 4
It is an amount of to get the Fructus Crataegi extract that obtains according to embodiment 1 method;
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 Fructus Crataegi extract 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
It is an amount of to get the Fructus Crataegi extract that obtains according to embodiment 1 method;
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, Fructus Crataegi extract 450g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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
It is an amount of to get the Fructus Crataegi extract that obtains according to embodiment 1 method;
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, Fructus Crataegi extract 300g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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 Fructus Crataegi extract 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, Fructus Crataegi extract 430g; Microcrystalline Cellulose and micropowder silica gel are added in the Fructus Crataegi extract, 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 Fructus Crataegi extract that obtains according to embodiment 1 method;
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 above-mentioned Fructus Crataegi extract, 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 Fructus Crataegi extract weight ratio are 7: 25 HPMC: PVP-K30 (2: 5) mixture is viscosity adjustment agent; Perhaps selection and Fructus Crataegi extract 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 the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC: PVP-K30 (2: 5) mixture, the Fructus Crataegi extract of 340g with the Fructus Crataegi extract 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 Fructus Crataegi extract, 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 Fructus Crataegi extract that obtains according to embodiment 1 method;
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 Fructus Crataegi extract (after amounting to dry weight, accounting for the 15wt% of master batch weight) and adds 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 Fructus Crataegi extract of 440g, with the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, use dehydrated alcohol that above-mentioned viscosity adjustment agent polyethylene glycol 6000 is formulated as the solution of concentration as 15wt%; Add in the Fructus Crataegi extract; 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 Fructus Crataegi extract that obtains according to embodiment 1 method;
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 Fructus Crataegi extract (after amounting to dry weight, accounting for the 15wt% of master batch weight) and adds 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 Fructus Crataegi extract of 500g, with the Fructus Crataegi extract 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, in the adding Fructus Crataegi extract, 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 Fructus Crataegi extract that obtains according to embodiment 1 method;
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 Fructus Crataegi extract (after amounting to dry weight, accounting for the 10wt% of master batch weight) and adds 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 Fructus Crataegi extract of 500g, with the Fructus Crataegi extract 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, in the adding Fructus Crataegi extract, 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 Fructus Crataegi extract that obtains according to embodiment 1 method;
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 Fructus Crataegi extract (after amounting to dry weight, accounting for the 10wt% of master batch weight) and adds 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 Fructus Crataegi extract of 800g, with the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, use dehydrated alcohol that above-mentioned viscosity adjustment agent polyethylene glycol 6000 is formulated as the solution of concentration as 15wt%; Add in the Fructus Crataegi extract; 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 Fructus Crataegi extract 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 Fructus Crataegi extract 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 450g; The Fructus Crataegi extract of 300g; With the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the Fructus Crataegi extract 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 Fructus Crataegi extract; 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 (2)
1. a Chinese medicinal granule that contains Fructus Crataegi extract is processed by Fructus Crataegi extract and pharmaceutically acceptable carrier, it is characterized in that it being to adopt following steps to prepare:
(1) it is an amount of to get Fructus Crataegi extract;
(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 Fructus Crataegi extract 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 450g; The Fructus Crataegi extract of 300g; With the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the Fructus Crataegi extract 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, in the adding Fructus Crataegi extract, after the mixing, adding 60% 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. method for preparing that contains the Chinese medicinal granule of Fructus Crataegi extract is characterized in that step is following:
(1) it is an amount of to get Fructus Crataegi extract;
(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 Fructus Crataegi extract 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 450g; The Fructus Crataegi extract of 300g; With the Fructus Crataegi extract weight ratio be 18: 25 polyethylene glycol 6000, perhaps be 7: 25 HPMC and PVP-K30 mixture, wherein HPMC with the Fructus Crataegi extract 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, in the adding Fructus Crataegi extract, after the mixing, adding 60% 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101503050A CN101439107B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing haw thorn extract and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2007101503050A CN101439107B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing haw thorn extract and preparation method thereof |
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| Publication Number | Publication Date |
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| CN101439107A CN101439107A (en) | 2009-05-27 |
| CN101439107B true CN101439107B (en) | 2012-07-04 |
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| CN2007101503050A Expired - Fee Related CN101439107B (en) | 2007-11-22 | 2007-11-22 | Chinese medicine granule containing haw thorn extract and preparation method thereof |
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| CN107875138B (en) * | 2016-09-30 | 2021-11-16 | 天士力医药集团股份有限公司 | Preparation method of spherical formula particles and related products |
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