CN102836237A - Integrally releasing Yang recuperating controlled and sustained release preparation and preparation method thereof - Google Patents
Integrally releasing Yang recuperating controlled and sustained release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN102836237A CN102836237A CN2012100147990A CN201210014799A CN102836237A CN 102836237 A CN102836237 A CN 102836237A CN 2012100147990 A CN2012100147990 A CN 2012100147990A CN 201210014799 A CN201210014799 A CN 201210014799A CN 102836237 A CN102836237 A CN 102836237A
- Authority
- CN
- China
- Prior art keywords
- controlled
- release
- preparation
- preparing
- yang
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention provides a preparation method for integrally controlling multiple components of the Yang recuperating controlled and sustained release preparation to release. Various types of controlled and sustained release preparations can be prepared by the controlled and sustained release preparation by utilizing osmotic pressure and membrane controlled release principles. The preparation method comprises the following steps of: adding starch, dextrin, water-soluble high-molecular polymer, hypertonic substances and other auxiliaries into the extract of the Yang recuperating prescription to prepare a tablet core; and coating the tablet core with the water-soluble polymer liquid containing a pore-forming agent, and poring to prepare an osmotic pump tablet; and preparing a microporous film coating tablet by adopting the high-molecular material and the pore-forming agent; and preparing controlled and sustained micropills, microspheres and small tablets by adopting the film controlled and sustained release material, or filling into hard capsule shells to prepare hard capsules. The invention also provides an integrally releasing Yang recuperating controlled and sustained release preparation, which can release multiple components of the drug in an integral and controlled way, so that the acting time of the medicament can be prolonged, the number of administration times can be reduced, and the compliance of clinical patient administration can be improved.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of controlled slow-release preparation of Chinese medicine compound, particularly relate to whole controlled slow-release preparation of multicomponent medicine of classical name side BUYANG HUANWU TANG prescription and preparation method thereof.
Background technology
BUYANG HUANWU TANG head is stated from Qing Dynasty's Wang Qingren errors in Medicine Corrected, and is complete square by Radix Astragali 60g, Radix Angelicae Sinensis 9g; Rhizoma Chuanxiong 6g, Radix Paeoniae Rubra 9g, Semen Persicae 9g; Flos Carthami 9g, Pheretima 9g forms, and has the function of QI invigorating, collateral dredging; Research afterwards shows that further it at antithrombotic, defying age, anti-brain bolt blood, antilipemic and regulate the effect that prevention and treatment are being arranged aspect the immunologic function, particularly all can play excellent prevention and therapeutical effect with convalescent period at ischemia apoplexy (cerebral infarction) acute attack stage and apoplexy early stage, and this side to compose total amount statistical moment half-life of moving be 7 hours; The patient's majority that the is suitable for comparison difficulty of taking medicine, the suitable controlled slow-release preparation that is prepared into, prolong drug action time; Reduce patient's medicining times, make it better comply with clinical demand, have great clinical application meaning and market value.
In the prior art with YANG invigorating also five sides be the basis; Add and subtract simply or the multi-flavor medical material, it is more to develop new pharmacologically active and Study of Clinical Application, is the basis with traditional BUYANG HUANWU TANG agent; It is carried out dosage form improve, like capsule, soft capsule, injection, fast-dissolved embolism-eliminating pulvis etc.In application number is 200710020874.3 Chinese patent, mention the BUYANG HUANWU TANG slow release formulation, but do not provide the technical scheme of any this dosage form of realization in the application documents.
In fact, the controlled slow-release preparation of preparation Chinese medicine compound still has many problems to need to solve, and the controlled slow-release preparation that preparation can the synchronous controlled release of multiple composition more need overcome many technical barriers, with and the complexity of appraisement system also remain further to be explored.
At present, single composition controlled slow-release preparation technology of preparing is day by day ripe, though the research of Chinese medicine controlled slow-release preparation is more and more, its research still still is in the starting stage, and the research degree of depth is not enough.Do not clean up fully as yet with the Chinese medicine compound controlled slow-release preparation technology of preparing problem that concerns because the Chinese medicine ingredients mechanism of action, total amount pharmacokinetics, total amount controlled slow-release preparation technology core technology, total amount quality evaluation system, Chinese crude drug steady quality etc. are a series of; The Chinese medicine controlled slow-release preparation of real ripe listing is less; Major part is single component variety, and the control slow release release formulation that embodies the Chinese medicine compound medication does not more have.
Chinese medicine belongs to the compound recipe medication more, is the mutual compatibility of multiple composition, and multiaction, multipath, many target spots, multi-level comprehensive function result, its curative effect constitute when by pharmacokinetic parameter, the medicine of each composition that effect coefficient determines jointly.The effect coefficient of right each composition is certain value by its physicochemical property decision, need not controlledly, so will prepare the controlled slow-release preparation of the former side requirement of Chinese medicine compound Cheng Hefu, pharmacokinetic parameter and the medicine constituent ratio of then tackling each composition are carried out integral body and controlled.Pharmacokinetic parameter divides configuration and input parameter; Controlled slow-release preparation can only change input parameter; Absorption equilibrium constant just, and Chinese medicine compound multicomponent pharmacokinetic parameter is because of compatibility each other, its configuration all becomes with input parameter; Therefore have only the ratio of strict each ingredient of control can guarantee that just the concentration ratio of all compositions in pharmacokinetic parameter and the body is stable; Its group effect could stable and controllable, and therefore as how the synchronous release of all compositions of the whole control of preparation technique Chinese medicine compound is the key core technology of the slow formulation preparation of Chinese medicine compound control, by vast medicament scientist is attracted attention.Obviously only apply mechanically simply that single composition is precisely controlled will to exist serious problems with evaluation model development Chinese medicine compound multicomponent controlled slow-release preparation.
Therefore; Desire is processed controlled slow-release preparation with Chinese medicine compound; Its guiding theory is: (many releases particle is the while release at random for whole controlled (multicomponent is synchronously with the form controlled release of stable total amount constituent ratio), corrosion (medicine and adjuvant dissolve releases simultaneously) synchronously and the complementary at random stripping of many particles; Produce complementation, general synchronization).
Present oligomict control slow release method mainly contains: 1. store the storehouse formula; 2. monoblock type; 3. peplos monoblock type; 4. be dispersed in formula in the bio-degradable polymer; 5. multicenter is with time control sustained-release administration system.Existing on the market Chinese medicine sustained-release preparation major part is used single composition medicine control slow release technology of preparing and is prepared from; Mostly be oral controlled slow-release preparation; Main dosage form has matrix tablet, film controlling type slow releasing tablet, multilayer tablet, floating in stomach sheet, bioadhesive tablet, microcapsule, microsphere, slow releasing capsule; Transdermal drug delivery system, slow-release micro-pill, bagged steeping drug, osmotic pump tablet etc., these preparations and technology of preparing not necessarily are applicable to the preparation of Chinese medicine compound controlled slow-release preparation.
Make multicomponent by the regularly controlled release of similar constituent ratio; Then necessarily require this drug-supplying system to control to the whole medicine drug release behavior of Chinese medicine compound; That is to say that the solution that can control behind Chinese medicine (compound recipe) the chip medicine dissolution is with the stable form release of total amount constituent ratio; Therefore depotting membrane hole control volume type drug delivery system is more satisfactory, like osmotic pump type, microporous membrane drug-supplying system;
When adopting whole skeleton administration, can be like medicine and substrate simultaneously by an outside to inside corrosion (separating), then medicine also can embody the multicomponent synchronously overall controlled release of Chinese medicine compound, but substrate needs water-soluble high-molecular material more, and inconvenience realizes slow controlled release target; As adopt the skeleton drug-supplying system of not corrosion of integral body, and each composition spreads stripping from framework material, and different because of the diffusion coefficient of each composition, the constituent ratio that also difficult and former side's decoction requires is identical, so the whole controllability of medicine is poor.So technology is not ideal Chinese medicine compound multicomponent control Atrigel;
, film controlled-release administrating system skeleton for not corrosion also can adopt the multicenter administering mode to realize the target of whole release; Like preparations such as micropill, microsphere, microcapsule, small pieces; Because multicenter stripping simultaneously; Solvent is prone to get into centers for making of pharmaceutical preparations, can remedy the inequality of single stripping particle center composition stripping, on integral macroscopic, can satisfy the requirement controlled simultaneously, that similarity is high.
Therefore, suitable Chinese medicine compound controlled slow-release preparation and technology of preparing mainly contain: 1. osmotic pump type controlled-release administrating system; 2. fenestra controlled-release administrating system; 3. control slow-release micro-pill, microsphere, microcapsule and small pieces; 4. floating in stomach is detained controlled-release administrating system etc.
Summary of the invention
In order to solve prior art problems, the inventor gropes through the arduousness practice of several years, after the characteristics of the present single composition controlled slow-release preparation preparation of systematic analysis " parameter is exclusive, precisely controlled, focuses on to modify the input pharmacokinetic parameters "; After having proposed Chinese medicine compound multicomponent controlled slow-release preparation preparation and should following the thinking of " whole controlled; corrosion synchronously; that many particles stripping at random are complementary "; Just summed up and founded YANG invigorating also the preparation principle and the method for five controlled slow-release preparations after having passed through repeatedly the failure of an experiment and success, proposed with the controlled or many particles of the minimum release whole unit multicomponent control slow release technology of preparing of complementary stripping at random.
Therefore, the object of the present invention is to provide the also method for preparing of five controlled slow-release preparations of a kind of whole YANG invigorating that discharges, this method for preparing comprises the steps:
A mixes medical material by following proportioning, 60 parts of the Radixs Astragali, 9 parts of Radix Angelicae Sinensis, 6 parts of Rhizoma Chuanxiongs, 9 parts of Radix Paeoniae Rubra, 9 parts in Semen Persicae, 9 parts on Flos Carthami, 9 parts of Pheretimas;
B extracts above-mentioned medical material water or organic solvent or its mixture as extracting solvent, filter then, obtains filtrating;
C with B step gained concentrating filter liquor after, precipitate with ethanol or centrifugalize obtain supernatant, concentrate drying gets extractum;
D adds acceptable accessories in C step gained extractum, the tabletting or process micropill of granulating then obtains label or ball core;
The E preparation contains the coating solution of slow releasing agent, porogen, and the consumption of this slow releasing agent is 0.5%～15% of a said extractum weight; The consumption of this porogen is 0%～2% of an extractum weight; Then this coating solution is sprayed onto said label or ball wicking surface, said art for coating condition is: 20～60 ℃ of coating temperature, coating solution flow velocity 10～80ml/min is until the weight increase by 0.1%～20% of tablet, micropill or microsphere.
Further, this method for preparing also comprises the steps:
Each makes a call to the hole that an aperture is 0.1～2.0mm to F in the above-mentioned upper and lower surface of coated tablet symmetry.
Further, obtain the tablet or micropill of coating after, can also comprise the steps:
The tablet of coating or micropill packed into make also the five kinds of stiffness in infant capsule controlled slow-release preparation of YANG invigorating in the hard capsule softgel shell.
Preferably, the extraction process condition of said B step is: extract solvent and select water or 10～90% ethanol-water solutions for use, the extraction solvent load is 3-20 a times of medical material weight; Extraction time is 1-5 time, and extraction time is 0.5～3 hour.
Preferably, the alcohol precipitation process condition of said C step is: concentration of alcohol 80～100%; Amount of ethanol is 2～10 times of extracting liquid volume; 4～48 hours precipitate with ethanol time.
Preferably, method for preparing according to claim 1 is characterized in that, the process conditions of the centrifugalize of said C step are: rotating speed is 1000～5000rpm, and centrifugation time is 5～30min.
Preferably, the acceptable accessories of said D step comprises and is selected from the combination of being made up of starch, pregelatinized Starch, dextrin, lactose, sodium chloride, calcium carbonate, calcium hydrogen phosphate, calcium sulfate, sucrose, mannitol, sorbitol, microcrystalline Cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, magnesium stearate, Pulvis Talci, Polyethylene Glycol.
Preferably, the slow releasing agent of said E step is selected from the combination of being made up of cellulose acetate, ethyl cellulose, ethylene-vinyl acetate copolymer, polyacrylic acid resin; Said porogen is selected from by the also combination formed of five extract water-soluble substanceses of Polyethylene Glycol, polyvinyl pyrrolidone, sodium lauryl sulphate, mannitol, lactose, glucose, fructose, carbamide, sucrose, sodium chloride, sodium bicarbonate, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, polysorbate 20, Eudragit L or YANG invigorating.
Preferably, the molecular weight of said Polyethylene Glycol is 400-20000.
The present invention also provides also five controlled slow-release preparations of a kind of whole YANG invigorating that discharges, and it is formed by method for preparing.
Further, the YANG invigorating that this integral body discharges also five controlled slow-release preparations is tablet, micropill, microsphere or capsule, and it can external stripping release synchronously in proportion in 0.5～10 hour, and the similarity of its finger printing is 0.5～1; Said preparation can reach the control slow release effect more than 12 hours in vivo.
Compare with method for preparing in the past, advantage of the present invention comprises at least:
1) controlled slow-release preparation that is obtained satisfies whole controlled, discharges synchronously or the complementary at random drug release behavior that discharges of many particles;
2) prepare the controlled slow-release preparation that BUYANG HUANWU TANG becomes synchronous release first, improve the compliance of clinical patient medication.
3) adopting first with multicomponent release unit is that the formulation preparation technology realizes the whole controlled target of multicomponent;
4) adopting with the complementary at random stripping in many particles center first is the target that the formulation preparation technology realizes the synchronous stripping of multicomponent.
5) adopt of the evaluation methodology of multicomponent finger printing similarity as the whole controlled stripping of controlled slow-release preparation, to YANG invigorating also five controlled slow-release preparations estimate.
And the method is suitable for preparations such as comprising osmotic pumps, fenestra controlled release preparation and film controlled release small pieces, micropill, microsphere, the release of many particles of microcapsule.Comprehensively above-mentioned; The present invention has not only cleaned up single composition controlled slow-release preparation theoretically and the multicomponent controlled slow-release preparation prepares theoretical boundary line; And searched out the drug release hole scope (with the membrane aperture that porogen was produced of 0.01%～2% extractum weight) of the controlled release of satisfied integral body unit needs, solve the international difficult problem of multicomponent whole controlled release synchronously.
Description of drawings
Fig. 1 YANG invigorating is the finger printing of the preferred embodiment of five controlled slow-release preparations also.
The drawing reference numeral explanation:
S1～S10 is respectively the finger printing of different time points sampling in 0.5,1.5,3,4,5,6,7,8,9,10 hour; S11 is the finger printing of composition sampling when dissolving entirely.
The specific embodiment
The objective of the invention is to propose the also method for preparing of five controlled slow-release preparations of a kind of whole YANG invigorating that discharges; Can make the whole controlled slow release of multiple composition in the compound recipe through this method; Embody the mutual compatibility of multiple composition, many target spots, multi-level comprehensive function effect, the characteristics of medical drugs in meeting.
Whole release of the present invention is meant that multiple ingredient discharges in proportion within a certain period of time synchronously.Controlled slow-release preparation according to the invention can drug release hole for control slow release means, like osmotic pumps,, promptly reach controlled-release effect when the quality of medicine is a zero-order release during much larger than the dissolved quality of saturated concentration; When drug concentrations is the one-level release during less than its saturated concentration, promptly reach slow release effect.The another kind of controlled slow-release preparation of the present invention is to be the small pieces or the micropill of control slow release means with the fenestra, and is relevant with porogen, when the porogen large usage quantity, produces the control slow release effect of osmotic pumps; Less when not having when porogen, then embody control slow release effect with the controlled master of being of diffusion coefficient.
Slow releasing agent of the present invention includes but not limited to cellulose acetate, ethyl cellulose, ethylene-vinyl acetate copolymer, polyacrylic acid resin; Porogen according to the invention includes but not limited to Polyethylene Glycol, polyvinyl pyrrolidone, sodium chloride, sucrose, mannitol, sodium lauryl sulphate, lactose, glucose, fructose, lactose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, carbamide.Porogen of the present invention includes but not limited to also five extract water-soluble substanceses of Polyethylene Glycol, polyvinyl pyrrolidone, sodium lauryl sulphate, mannitol, lactose, glucose, fructose, carbamide, sucrose, sodium chloride, sodium bicarbonate, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, polysorbate 20, Eudragit L or YANG invigorating.
Following conjunction with figs. and the preferred embodiments of the present invention, further setting forth the present invention is to reach the technological means that predetermined goal of the invention is taked.
Embodiment 1 YANG invigorating is the preparation of five full formula extractions 1 also
Get Radix Astragali 60g.Radix Angelicae Sinensis 9g, Rhizoma Chuanxiong 6g, Radix Paeoniae Rubra 9g, Semen Persicae 9g, Flos Carthami 9g; Pheretima 9g extracted about 2 hours with 8 times of amount distilled water, filtered, and filtering residue added 8 times of amount distilled water second extraction about 1 hour again, filtered; Merge filtrating twice, concentrate and obtain also five full side's extracting solution of YANG invigorating, adopt 95% ethanol precipitate with ethanol, transition is filtered; Filtrating concentrates, and recovery ethanol gets also five full side prescription fluid extracts of YANG invigorating, the dry also five full formula extractions 1 of YANG invigorating that get.
Embodiment 2 YANG invigoratings are the preparation of five full formula extractions 2 also
Get Radix Astragali 6kg.Radix Angelicae Sinensis 0.9kg, Rhizoma Chuanxiong 0.6kg, Radix Paeoniae Rubra 0.9kg, Semen Persicae 0.9kg; Flos Carthami 0.9kg, Pheretima 0.9kg extracted about 3 hours with 20 times of amount distilled water, filtered; Filtering residue added 15 times of amount distilled water second extraction about 2 hours again, filtered, and filtering residue adds 10 times of amount distilled water again and extracted about 1 hour for three times, merges filtrating three times; Concentrate and obtain also five full side's extracting solution of YANG invigorating, adopt 80% ethanol precipitate with ethanol, centrifugalize; Supernatant again in 70～75 ℃ of following oven dryings, gets also five full formula extractions 2 of YANG invigorating in about 60 ℃ of following concentrating under reduced pressure.
Embodiment 3 YANG invigoratings are the preparation of five full formula extractions 3 also
Medical material takes by weighing by following proportioning: 60 parts of the Radixs Astragali, 9 parts of Radix Angelicae Sinensis, 6 parts of Rhizoma Chuanxiongs, 9 parts of Radix Paeoniae Rubra, 9 parts in Semen Persicae, 9 parts on Flos Carthami, 9 parts of Pheretimas.Extracted about 2 hours with 15 times of amount 50% alcoholic solution then; Filter, filtering residue added 8 times of amount 50% alcoholic solution second extraction about 1.5 hours again, filtered; Filtering residue adds 3 times of amount 50% ethanol again and extracted about 1 hour for three times; Merge filtrating three times, obtain also five full side's extracting solution of YANG invigorating in 60 ℃ of following vacuum concentration, the relative density of this extracting solution is 1.1～1.3; Use the dehydrated alcohol sedimentation method then, about 48 hours,,, get also five full formula extractions 3 of YANG invigorating then in 70～75 ℃ of following vacuum dryings again in 60 ℃ of following concentrating under reduced pressure.
Embodiment 4 YANG invigoratings are the preparation of five full formula extractions 4 also
Get Radix Astragali 120g.Radix Angelicae Sinensis 18g, Rhizoma Chuanxiong 12g, Radix Paeoniae Rubra 18g, Semen Persicae 18g, Flos Carthami 18g; Pheretima 18g adds the decoction of 8 times of amounts of medical material, 10% ethanol and extracted one hour, filters, and filtering residue adds 8 times of amounts of medical material, 10% ethanol again and decocts extraction one hour, filters; Merge secondary filtrating, be concentrated into 260ml, add ethanol precipitation in the concentrated solution, add ethanol 390ml first, make the alcohol amount about 60% that contains; Be precipitated to not have basically and newly precipitate generation, filter, filtrating adds a certain amount of ethanol again to be made and contains the alcohol amount and reach about 85%, precipitates about 24 hours, filters; Filter cake carries out drip washing with 100ml ethanol, is incorporated in the filtrating, reclaims ethanol with Rotary Evaporators, and to extracting solution concentrate the about 45g of fluid extract, promptly get extract 4.
Embodiment 5 YANG invigoratings are the preparation of five control slow releasing tablet labels also
Get the about 90g of said extracted thing, add 46g starch, the 12g dextrin, mixing, it is about 8% that 70 ℃ of aeration-drying to water content are lower than, the about 112g of dry extract, pulverizing extractum is crossed 40 mesh sieves, packs subsequent use.
Get also five full presciption medicine powder of the YANG invigorating that prepared, add sodium chloride 5-10g, microcrystalline Cellulose 7-12g; Suitably grind and make mix homogeneously, spray into an amount of 95% ethanol, 10 mesh sieves are granulated; Place drying baker interior behind 60 ℃ of aeration-drying 1.5h, 14 mesh sieve granulate make fine powder content be no more than 20%; Add 1%～2% magnesium stearate as fluidizer, mixing, tabletting gets label.
The also preparation of five osmotic pump controlled slow-release tablets of embodiment 6 YANG invigoratings
Take by weighing 25～35g cellulose acetate, it is dissolved in the acetone of 1L, obtain the acetone soln that concentration is the cellulose acetate of 25～35g/L, the PEG4000 that adds cellulose acetate quality 2%～20% promptly gets coating solution as porogen; Get the label of having suppressed; With carrying out coating on above-mentioned coating solution even spraying to the label; But the method for coating is any implementation method in the prior art; Heavily increase by 3% until sheet, then respectively in the upper and lower surface symmetry of coated tablet each to make a call to an aperture be 600 microns hole, promptly get also five osmotic pump controlled slow-release tablets of YANG invigorating.
The embodiment 7 whole also preparations of five osmotic pump controlled slow-release tablets of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, add sucrose 5-10g, microcrystalline Cellulose 7-12g; Suitably grind and make mix homogeneously, spray into 95% ethanol, 10 mesh sieves are granulated; Place drying baker interior behind 60 ℃ of aeration-drying 1.5h, 14 mesh sieve granulate make fine powder content be no more than 20%; Add 1%～2% magnesium stearate as fluidizer, mixing, tabletting gets label.
The acetone soln of the cellulose acetate of the about 25-35g/L of preparation; The PEG6000 that adds cellulose acetate quality 2%～20% gets compressed cores, spray coating as porogen; Beat the about 0.6mm aperture of diameter in the tablet both sides of coating respectively, make also five osmotic pump controlled slow-release tablets of YANG invigorating.
The embodiment 8 whole also preparations of five osmotic pump controlled slow-release tablets of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, add mannitol 5-10g, microcrystalline Cellulose 7-12g; Suitably grind and make mix homogeneously, spray into an amount of 95% ethanol, 10 mesh sieves are granulated; Place drying baker interior behind 60 ℃ of aeration-drying 1.5h, 14 mesh sieve granulate make fine powder content be no more than 20%; Add 1%～2% magnesium stearate as fluidizer, mixing, tabletting gets label.
The acetone soln of the cellulose acetate of the about 25-35g/L of preparation; The PEG2000 that adds cellulose acetate quality 2%～20% gets compressed cores, spray coating as porogen; Beat the about 0.6mm aperture of diameter in the tablet both sides of coating respectively, make also five osmotic pump controlled slow-release tablets of YANG invigorating.
The embodiment 9 whole also preparations of five osmotic pump controlled slow-release tablets of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, add sodium chloride 5-10g, hydroxypropyl emthylcellulose 7-12g; Suitably grind and make mix homogeneously, spray into an amount of 95% ethanol, 10 mesh sieves are granulated; Place drying baker interior behind 60 ℃ of aeration-drying 1.5h, 14 mesh sieve granulate make fine powder content be no more than 20%; Add 1%～2% magnesium stearate as fluidizer, mixing, tabletting gets label.
The acetone soln of the cellulose acetate of the about 25-35g/L of preparation; The PEG6000 that adds cellulose acetate quality 2%～20% gets compressed cores, spray coating as porogen; Beat the about 0.6mm aperture of diameter in the tablet both sides of coating respectively, make also five osmotic pump controlled slow-release tablets of YANG invigorating.
The embodiment 10 whole also preparations of five microporous membrane control sustained release coating tablets of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, spray into an amount of 95% ethanol, granulate; 60 ℃ of aeration-dryings, granulate, the control fine powder content makes and meets the tabletting requirement; The magnesium stearate of adding 1%～2%; Mixing, tabletting promptly get also five labels of YANG invigorating, with cellulose acetate, ethyl cellulose, ethylene-vinyl acetate copolymer, polyacrylic acid resin as the coating membrane material; Add PEG class, PVP, PVA, sodium lauryl sulphate, lactose or a small amount of YANG invigorating water-soluble substances such as five extracts also account for coating membrane quality of materials 2%～20% in the coating solution, the label coating is promptly got also five microporous membrane control sustained release coating tablets of YANG invigorating.
The embodiment 11 whole also preparations of five film-controlled slow-release small pieces of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, add 3-6g sodium chloride, the 4-8g hydroxypropyl emthylcellulose; Suitably grind and make mix homogeneously, spray into 95% ethanol, 16 mesh sieves are granulated; Place drying baker interior behind 60 ℃ of aeration-drying 1.5h, 20 mesh sieve granulate make fine powder content be no more than 20%; Add 1%～2% magnesium stearate as fluidizer, mixing is pressed into the little label of diameter 4mm.
The acetone soln of preparation 25-35g/L cellulose acetate; The PEG4000, polysorbate 20 or the Eudragit L that add cellulose acetate quality 2%～20% are as porogen; Get part small pieces core fluidized coating; Other gets the little label of part, carries out fluidized coating with the acetone soln of Eudragit RL 100 and Eudragit RS 100, makes also five film controlled release fertilizer small pieces of YANG invigorating.
The embodiment 12 whole also preparations of five film-controlled slow-release micropills of YANG invigorating that discharge
Get also five full side's extractum medicated powder of the YANG invigorating that prepared, add 3-6g sodium chloride, the 4-8g hydroxypropyl emthylcellulose; Suitably grind and make mix homogeneously; With 40 order sucrose particles is core, is binding agent to contain alcoholic acid syrup, is sprinkled into 100 order fine drug powders under rolling; Processing diameter is the pill core that contains of 1.4mm, drying.
The Eudragit RL 100 of preparation 5～30% equivalent and the isopropyl alcohol of Eudragit RS 100: acetone (60:40) solution; The PEG that adds polymer quality 2%～20% processes coating solution; To the micropill fluidized coating; Process the micropill that diameter is 1.5mm, or make also five film-controlled slow-release pellet preparations of YANG invigorating in the hard capsule of packing into.
The embodiment 13 whole also preparations of five slow releasing capsule of YANG invigorating that discharge
The YANG invigorating that the integral body of embodiment 11,12 gained is discharged is pack into 0#, 1# or 2# capsule of five control slow release small pieces or micropill or its mixture also, the YANG invigorating five control slow releasing capsule also of whole release.
Embodiment 14 external dissolution tests and finger printing similarity thereof are measured
The 2nd method of pressing in 2010 editions two appendix dissolution methods of Chinese Pharmacopoeia is measured its release degree, and respectively 0.5,1.5,3,4,5,6,7,8,9, measure its release degree during 10h, the result sees table 1.
The release degree (%) of the external dissolution test of table 1 preferred embodiment of the present invention.
Visible by table 1, more than each preferred embodiment YANG invigorating also five controlled slow-release preparations in 10 hours, reached the purpose that delays to discharge.
Hydrochloric acid solution with 0.1mol/L is a dissolution medium; Rotating speed is 100r/min; 37.0 ℃ of temperature, in accordance with the law operation and respectively 0.5,1.5,3,4,5,6,7,8,9, during 10h and when composition dissolves entirely, take a sample respectively, 5mL takes a sample at every turn; Replenish the isopyknic dissolution medium of isothermal simultaneously, filter and promptly get testing sample.Adopt chromatographic fingerprints of Chinese materia medica similarity evaluation system to carry out similarity evaluation, high-efficient liquid phase chromatogram is seen Fig. 1, and chromatographic condition is: the C18 post is the eluent gradient eluting with acetonitrile and 1% acetic acid water; It is 264nm that UV detects wavelength, and the similarity evaluation result of the external dissolution test finger printing of the preferred embodiment of the present invention sees table 2.
The similarity of the external dissolution test finger printing of table 2 preferred embodiment of the present invention
Visible by table 2, the finger printing similarity of the external dissolution test of each preferred embodiment of the present invention meets the whole requirement of release in proportion between 0.5～1, has realized that basically many compositions divide the effect that discharges synchronously.
The above only is the preferred embodiments of the present invention; Not being that the present invention is done any pro forma restriction, though the present invention with the preferred embodiment exposure as above, yet is not in order to limit the present invention; Anyly be familiar with the professional and technical personnel; In the scope that does not break away from technical scheme of the present invention, make a little change or be modified to the equivalent embodiment of equivalent variations when the technology contents of above-mentioned announcement capable of using, be the content that does not break away from technical scheme of the present invention in every case;, all still belong in the scope of technical scheme of the present invention any simple modification, equivalent variations and modification that above embodiment did according to technical spirit of the present invention.
Claims (10)
1. a whole YANG invigorating that the discharges method for preparing of five controlled slow-release preparations also is characterized in that, comprises the steps:
A mixes medical material by following proportioning, 60 parts of the Radixs Astragali, 9 parts of Radix Angelicae Sinensis, 6 parts of Rhizoma Chuanxiongs, 9 parts of Radix Paeoniae Rubra, 9 parts in Semen Persicae, 9 parts on Flos Carthami, 9 parts of Pheretimas;
B extracts above-mentioned medical material water or organic solvent or its mixture as extracting solvent, filter then, obtains filtrating;
C with B step gained concentrating filter liquor after, precipitate with ethanol or centrifugalize obtain supernatant, concentrate drying gets extractum;
D adds acceptable accessories in C step gained extractum, the tabletting or process micropill of granulating then obtains label or ball core;
The E preparation contains the coating solution of slow releasing agent, porogen, and the consumption of this slow releasing agent is 0.5%～15% of a said extractum weight; The consumption of this porogen is 0%～2% of a said extractum weight; Then this coating solution is sprayed onto said label or ball wicking surface, obtains tablet or micropill, said art for coating condition is: 20～60 ℃ of coating temperature, coating solution flow velocity 10～80ml/min is until the weight increase by 0.1%～20% of this tablet or micropill.
2. a method for preparing as claimed in claim 1 is characterized in that, also comprises the steps:
Each makes a call to the hole that an aperture is 0.1～2.0mm to F in the above-mentioned upper and lower surface of coated tablet symmetry.
3. a method for preparing as claimed in claim 1 is characterized in that, also comprises the steps:
F will be tablet or the micropill of coating pack into and make also the five kinds of stiffness in infant capsule controlled slow-release preparation of YANG invigorating in the hard capsule softgel shell.
4. according to the described method for preparing of claim 1～3, it is characterized in that the extraction process condition of said B step is: extract solvent and select water or 10～90% ethanol-water solutions for use, the extraction solvent load is 3-20 a times of medical material weight; Extraction time is 1-5 time, and extraction time is 0.5～3 hour.
5. according to the described method for preparing of claim 1～3, it is characterized in that the alcohol precipitation process condition of said C step is: concentration of alcohol 80～100%; Amount of ethanol is 2～10 times of extracting liquid volume; 4～48 hours precipitate with ethanol time.
6. according to the described method for preparing of claim 1～3, it is characterized in that the process conditions of the centrifugalize of said C step are: rotating speed is 1000～5000rpm, and centrifugation time is 5～30min.
7. according to the described method for preparing of claim 1～3; It is characterized in that the acceptable accessories of said D step comprises and is selected from the combination of being made up of starch, pregelatinized Starch, dextrin, lactose, sodium chloride, calcium carbonate, calcium hydrogen phosphate, calcium sulfate, sucrose, mannitol, sorbitol, microcrystalline Cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, magnesium stearate, Pulvis Talci, Polyethylene Glycol.
8. according to the described method for preparing of claim 1～3, it is characterized in that the slow releasing agent of said E step is selected from the combination of being made up of cellulose acetate, ethyl cellulose, ethylene-vinyl acetate copolymer, polyacrylic acid resin; Said porogen is selected from by the also combination formed of five extract water-soluble substanceses of Polyethylene Glycol, polyvinyl pyrrolidone, sodium lauryl sulphate, mannitol, lactose, glucose, fructose, carbamide, sucrose, sodium chloride, sodium bicarbonate, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, polysorbate 20, Eudragit L or YANG invigorating.
9. according to Claim 8 method for preparing is characterized in that the molecular weight of said Polyethylene Glycol is 400-20000.
10. a whole YANG invigorating that discharges five controlled slow-release preparations also; It is characterized in that; It is obtained by each described method for preparing in the claim 1 to 9, said preparation can be in 0.5～10 hour external stripping release synchronously in proportion, the similarity of its finger printing is 0.5～1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210014799.0A CN102836237B (en) | 2012-01-18 | 2012-01-18 | YANG invigorating also five controlled slow-release preparations and preparation method thereof of a kind of entirety release |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210014799.0A CN102836237B (en) | 2012-01-18 | 2012-01-18 | YANG invigorating also five controlled slow-release preparations and preparation method thereof of a kind of entirety release |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102836237A true CN102836237A (en) | 2012-12-26 |
| CN102836237B CN102836237B (en) | 2015-09-30 |
Family
ID=47364140
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210014799.0A Active CN102836237B (en) | 2012-01-18 | 2012-01-18 | YANG invigorating also five controlled slow-release preparations and preparation method thereof of a kind of entirety release |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102836237B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951965A (en) * | 2017-11-28 | 2018-04-24 | 枣阳千里香食品有限公司 | A kind of Chinese medicine composition for treating apoplexy hemiplegia sequela |
| CN111658696A (en) * | 2020-07-31 | 2020-09-15 | 李志林 | Traditional Chinese medicine preparation for treating thrombus and preparation method thereof |
| CN115531479A (en) * | 2022-11-14 | 2022-12-30 | 河南中医药大学 | Traditional Chinese medicine composition for treating senile cerebral infarction and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872179A (en) * | 2005-06-03 | 2006-12-06 | 天津天士力制药股份有限公司 | Microspheres in use for injection of Chinese traditional medicine of containing astragalus root, and preparation method |
| CN1903267A (en) * | 2006-08-05 | 2007-01-31 | 李华林 | Traditional Chinese medicine decoction Buyang Xiaoshuan Huanwu Tang for tonifying yang and dissolving thrombus |
| CN101036705A (en) * | 2007-04-10 | 2007-09-19 | 邵旭 | Buyang huanwu gantong medicine for preventing and curing cardiovascular or cerebrovascular disease and the agent and the method for preparing the same |
| CN101856337A (en) * | 2010-05-28 | 2010-10-13 | 中国科学院上海药物研究所 | Novel penetration and controlled-release medicament delivery system and preparation method thereof |
| CN101966203A (en) * | 2009-07-28 | 2011-02-09 | 安徽中医学院 | Study and application of release technique of effective compound group of traditional Chinese Medical prescription |
-
2012
- 2012-01-18 CN CN201210014799.0A patent/CN102836237B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872179A (en) * | 2005-06-03 | 2006-12-06 | 天津天士力制药股份有限公司 | Microspheres in use for injection of Chinese traditional medicine of containing astragalus root, and preparation method |
| CN1903267A (en) * | 2006-08-05 | 2007-01-31 | 李华林 | Traditional Chinese medicine decoction Buyang Xiaoshuan Huanwu Tang for tonifying yang and dissolving thrombus |
| CN101036705A (en) * | 2007-04-10 | 2007-09-19 | 邵旭 | Buyang huanwu gantong medicine for preventing and curing cardiovascular or cerebrovascular disease and the agent and the method for preparing the same |
| CN101966203A (en) * | 2009-07-28 | 2011-02-09 | 安徽中医学院 | Study and application of release technique of effective compound group of traditional Chinese Medical prescription |
| CN101856337A (en) * | 2010-05-28 | 2010-10-13 | 中国科学院上海药物研究所 | Novel penetration and controlled-release medicament delivery system and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 中华人民共和国药典委员会: "《卫生部颁药品标准中药成方制剂第11册》", 31 December 1996 * |
| 段晓鹏等人: "补阳还五汤指纹图谱总量统计矩加合性的研究", 《中国中药杂志》 * |
| 贺福元等: "中药控缓释制剂研制若干基础理论问题的研究", 《中成药》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951965A (en) * | 2017-11-28 | 2018-04-24 | 枣阳千里香食品有限公司 | A kind of Chinese medicine composition for treating apoplexy hemiplegia sequela |
| CN111658696A (en) * | 2020-07-31 | 2020-09-15 | 李志林 | Traditional Chinese medicine preparation for treating thrombus and preparation method thereof |
| CN115531479A (en) * | 2022-11-14 | 2022-12-30 | 河南中医药大学 | Traditional Chinese medicine composition for treating senile cerebral infarction and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102836237B (en) | 2015-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101138554B (en) | Effervescence dispersible tablet | |
| US20160303178A1 (en) | Pharmaceutical composition, method for preparing the same and use thereof | |
| CN101085024A (en) | Traditional Chinese medicinal composition containing red sage root and ginkgo leaves and its preparation | |
| CN102836237B (en) | YANG invigorating also five controlled slow-release preparations and preparation method thereof of a kind of entirety release | |
| CN102319225B (en) | Trimetazidine hydrochloride sustained release tablet and preparation method thereof | |
| CN101890063B (en) | Chinese medicament for reducing blood sugar and preparation method thereof | |
| CN103908484A (en) | Tripterygium wilfordii plastic for treating rheumatoid arthritis and preparation method thereof | |
| CN100463671C (en) | Vagina effervescent tablets contg. callicarpa nudiflora, and its prepn. method | |
| CN103271978A (en) | Ginkgo leaf compound preparation for resisting oxygen deprivation and glucose deprivation and treating altitude sickness | |
| CN101085006A (en) | Composition containing kudzuvine root for treating cardiovascular diseases and its preparation | |
| CN112569190B (en) | Oral administration preparation of pulsatilla chinensis saponin B4 and preparation method thereof | |
| CN101085192B (en) | Pulse engendendering active component composition and its preparation | |
| CN110075080B (en) | 3D printing instant tablet of traditional Chinese medicine extract and preparation method thereof | |
| CN101085027A (en) | Traditional Chinese medicinal composition containing red sage root and kudzuvine root and its preparation | |
| CN102058765A (en) | Chinese medicine preparation for treating cirrhosis and preparation method thereof | |
| CN103494916B (en) | Traditional Chinese medicine composition with effect of reducing blood sugar, as well as preparation method and application thereof | |
| CN102579536A (en) | Enteric Panax Notoginseng total saponin preparation and preparation method thereof | |
| CN101244068B (en) | Hemsleyadin sustained-release preparation | |
| CN100358508C (en) | Delay, control release drug of prepared aconite root which can regulate the function of middle-warmer, and its preparation method | |
| CN1788738B (en) | Medicinal preparation containing volatile oil and preparing method thereof | |
| CN101085081A (en) | Composition containing fructus aurantii for treating cardiovascular diseases and its preparation | |
| KR100735904B1 (en) | Tablet composition containing extract of natural herbal plants and its manufacturing process | |
| CN116115669A (en) | Pharmaceutical composition for treating myocardial ischemia and preparation method thereof | |
| CN101085007B (en) | Composition containing erigeron breviscapus for treating cardiovascular diseases and its preparation | |
| CN101199543A (en) | Compound for medicine by protogen and cobalamin activity component, preparing method and function thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |