CN103655585A - Gastrodin controlled release preparation and preparation method thereof - Google Patents
Gastrodin controlled release preparation and preparation method thereof Download PDFInfo
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Abstract
The invention provides a gastrodin controlled release preparation. The gastrodin controlled release preparation comprises a quick release part with high bioavailability and a controlled release part, wherein the gastrodin (gastrodin I) of the quick release part accounts for 30%-60% of the total weight of the gastrodin in the controlled release preparation, and the gastrodin (gastrodin II) of the controlled release part accounts for 40%-70% of the total weight of the gastrodin in the controlled release preparation. Single dose of the gastrodin controlled release preparation comprises 100-800mg of gastrodin, preferably, 300-600mg. In initial releasing stage, the gastrodin controlled release preparation is released through special quick release technology, thus accelerating the onset time, improving the bioavailability, and achieving the purpose of rapidly working; in middle and last releasing phases, the gastrodin controlled release preparation is released by controlled release technology, thus maintaining stable drug release amount, keeping stable blood concentration, improving the treatment effect of the drug, and lowering the toxic and side effects. The preparation is not affected to be released and absorbed in body by pH value and food in the body, guarantees to have slightly different treatment effect in different individuals under different conditions, and has important clinical application value. The invention provides a preparation method for the gastrodin controlled release preparation, and is applicable to industrial application.
Description
Technical field
The present invention relates to pharmaceutical preparation, be specifically related to a kind of controlled release preparation, relate in particular to a kind of control released gastrodin preparation and preparation method thereof.
Background technology
Chemistry 4-methylol benzene-β-D pyranglucoside by name of gastrodine.Conventionally, gastrodine extracts and obtains from the dry root piece of orchid Rhizoma Gastrodiae.Gastrodine has good calmness and soporific function, and neurasthenia, insomnia, headache symptom are had to mitigation, also can convulsion, anxiety, and can increase cerebral blood flow, reduce vascular resistance, improve vertebral-basilar artery insufficiency, there is neuroprotective.
Gastrodine has been widely used in clinical, and multiclass disease is had to obvious therapeutic effect.Chen Lifang (Clinical observation of gastrodine injection on treatment vertebral-basilar artery insufficiency [J]; Tianjin pharmacy; 06 phase in 2005) by 75 routine vertebro-basilar artery insufficiency patients, be divided at random Therapeutic Efficacy of Gastrodin group 35 example and matched group 40 examples, compare two groups of curative effects, result shows Therapeutic Efficacy of Gastrodin group total effective rate 88.6%, apparently higher than matched group (P<0.01), and have no obvious adverse reaction.Wei Wenshi, Chang Jie (the curative effect of different way of administration gastrodine injection to acute cerebral infarction patient, Shanghai medicine 2006.27 volume o. 11ths, 515～516 pages) clinical efficacy of observation different modes of administration gastrodine injection to acute cerebral infarction patient, 65 routine patients are divided into Therapeutic Efficacy of Gastrodin group (intravenous drip) 35 example and matched group (intramuscular injection) 30 examples at random, two groups all can be improved curative effect, treatment group total effective rate is 85.7%, matched group is 66.7%, hemorheology index reduces, relatively front with treatment, difference significance (P<0.05), show that gastrodine injection is safe and effective medicine for treatment acute cerebral infarction, and intravenously administrable curative effect is better than intramuscular injection.Sun Yanmei, Zhao Xiaojing, Wang great Li (Clinical observation of gastrodine injection on treatment vascular headache observation of curative effect [J]. China is comprehensively clinical, 2007,23 (12): 121-122.) 104 routine vascular headache patients are divided at random to each 52 examples of Clinical observation of gastrodine injection on treatment group and matched group, matched group adopts routine medication, and treatment group gives Clinical observation of gastrodine injection on treatment, effectively, effective percentage is 86.54% to treatment group 45 examples; Effectively, effective percentage is 76.90% to matched group 40 examples.Lu Yuhong (gastrodine injection associating nifedipine treatment aged hypertensives clinical observation, practical medical technologies magazine 14 11 phases of volume in 2007) 75 routine aged patients with hypertensions are divided into pure Western medicine group (38 example), Chinese medicine and western medicine group (37 example) at random, pure Western medicine group is oral to 30 milligrams of nifedipines, 2 times/day, Chinese medicine and western medicine group, except oral to nifedipine 30mg, 2 times/day, is separately given gastrodine injection 0.6g intravenous drip, 1 times/day, be 2 weeks the course for the treatment of; The rear pure Western medicine group for the treatment of and Chinese medicine and western medicine group syndrome are improved total effective rate and are respectively 60.5% and 86.5%.Jin Shanji, inscription on ancient bronze objects dragon are (with Clinical observation of gastrodin injection for diabetic peripheral neuropathy, modern medicine health the 19th phase of 22 volumes in 2006,2923 pages) the routine Diabetic Peripheral god of observation 83 pathological changes patients, diabetic diet and application hypoglycemic medicine are controlled blood glucose, normal saline 250mL adds gastrodine injection 80O～1000mg, 1 intravenous drip every day; 15 routine DPN patients are matched group, and diabetic diet and application hypoglycemic drug are controlled blood glucose; Effective 43 examples of observation group (51.81%), effective 23 examples (27.71%), invalid 17 examples (20.48%), total effective rate 79.52%, matched group symptom is all without improving.
At present, it is injection that gastrodine is used many clinically, and gastrodine is the monomer extracting in Chinese crude drug Rhizoma Gastrodiae, comparatively speaking, impurity wherein may be many, although refining through associated process steps such as purification, doing injection still has larger risk.Once there is report (Jiang Zhaorong, Gu Shengwang gastrodine injection cause the routine < < of systemic anaphylaxis dermatitis 1 Anhui medicine > > the 2nd phase in the 2010) people that pretends illness to occur the symptom of systemic anaphylaxis.And it is many that Chinese medicine produces the example of severe allergic reaction in recent years, explore the impurity index that its main cause is Chinese crude drug extract and be difficult to control.Although the preparation that the gastrodine of existing chemosynthesis is made listing, the difference in quality of each producer is larger.For example, endotoxin content in gastrodine injection, the fixed endotoxin content standard of some producers is: with respect to the endotoxic content of every 1mg gastrodine, be less than 0.15EU, and the standard of some producer is: with respect to the endotoxic content of every 1mg gastrodine, be less than 0.20-0.25EU.Therefore,, for fear of the insecurity of clinical practice, develop a kind of gastrodine preparation that meets the oral administration of clinical practice requirement and be very important.
The pharmacokinetic studies of gastrodine shows: after Healthy People intravenous injection gastrodine, distribution in human body is comparatively rapid, eliminating half-life T1/2 is about 4.16 hours, be difficult for producing and accumulating in vivo, be desirable quick acting medicine, the function curve of blood drug level one time graph and two-compartment model meets.Therefore, the clinical practice of gastrodine preparation is more excellent is the mode of selecting intravenous drip, so both can make to treat quick acting, and this effect can maintain the regular hour simultaneously.For the mode of the above-mentioned application of gastrodine clinically, the slow releasing preparation of exploitation gastrodine is obviously proper and favourable.Chinese patent 200510048255.6 and 200610092126.1, has described a kind of hydrogel matrix tablet that hydroxypropyl emthylcellulose is substrate of take, to reach the effect of slow release.Chinese patent 200610169151.5 has been described a kind of slow release micro-pills containing gastrodin and preparation method thereof, and this patent is controlled the release of gastrodine with film control techniques.Chinese patent 200610070953.0 has been described a kind of control released gastrodin preparation that uses osmotic pumps technology.Although according to these patented technologies, can prepare the gastrodine preparation with slow release effect,, according to clinical practice, require, remain inappropriate, because the onset speed of these preparations is slower, be unfavorable for using clinically.How to make gastrodine reach rapidly the valid density that treatment needs after oral, can make again this therapeutic effect maintain the regular hour, this is for application clinically, to need and problem anxious to be resolved at present simultaneously.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, needs the control delivery formulations of research design gastrodine for clinical practice.
The invention provides a kind of control released gastrodin preparation.
Control released gastrodin preparation of the present invention is comprised of immediate release section and the slow-released part of high bioavailability.Wherein the gastrodine of immediate release section (gastrodine I) accounts for the 30%-60% of gastrodine total amount in controlled release preparation, preferably 40%-50%; Slow-released part gastrodine (gastrodine II) accounts for the 40%-70% of gastrodine total amount in controlled release preparation, preferably 50%-60%.
The controlled release preparation of gastrodine of the present invention, its single-dose preparations contains gastrodine 100-800mg, preferably 300-600mg.
In control released gastrodin preparation of the present invention, described immediate release section is comprised of gastrodine I and the pharmaceutical carrier as active component; Described pharmaceutical carrier comprises diluent, disintegrating agent, lubricant and dispersant.Wherein diluent is selected from as one or more in microcrystalline Cellulose, starch, mannitol, sorbitol or lactose.Disintegrating agent is selected from as one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose or carboxymethyl starch sodium.Lubricant is selected from one or more in magnesium stearate, stearic acid, polyethylene glycol 6000, sodium lauryl sulphate or sodium stearyl fumarate.Dispersant is selected from one or more in polyvidone, hypromellose, hyprolose, Polyethylene Glycol, Polysorbate and polyoxyethylene hydrogenated Oleum Ricini.The weight proportion of described gastrodine I and disintegrating agent is 1.25:1-20:1, preferably 2.5:1-10:1; The weight proportion of gastrodine I and dispersant is 1:10-10:1, preferably 1:3-6:1; The weight proportion of gastrodine I and diluent is 1:8-3.5:1; The weight proportion of gastrodine I and lubricant is 5:1-75:1.
In control released gastrodin preparation of the present invention, described slow-released part is comprised of gastrodine II and the pharmaceutical carrier as active component; Described pharmaceutical carrier comprises diluent, lubricant, antiplastering aid, dispersant and macromolecular material.Wherein diluent is selected from as one or more in microcrystalline Cellulose, starch, mannitol, sorbitol or lactose.Lubricant is selected from one or more in magnesium stearate, stearic acid, polyethylene glycol 6000, sodium lauryl sulphate or sodium stearyl fumarate.Antiplastering aid is selected from one or more in Pulvis Talci or glyceryl monostearate.Dispersant is selected from one or more in polyvidone, hypromellose, hyprolose, Polyethylene Glycol, Glyceryl Behenate, Polysorbate and polyoxyethylene hydrogenated Oleum Ricini.Macromolecular material is selected from one or more in polyvinyl acetate, ethyl cellulose, polyacrylic resin, cellulose acetate, hypromellose, hyprolose, polyoxyethylene, sodium alginate.The weight proportion of described gastrodine II and disintegrating agent is 1:10-10:1, preferably 1:3-6:1; The weight proportion of gastrodine II and macromolecular material is 1:5-10:1, preferably 1:2-7:1; The weight proportion of gastrodine II and diluent is 1:8-3.5:1; The weight proportion of gastrodine II and lubricant is 5:1-75:1.
Control released gastrodin preparation of the present invention, can select but be not limited to following dosage form: single-layer sheet, double-layer tablet and capsule.Another object of the present invention has been to provide the preparation method of described a kind of control released gastrodin preparation.
The invention provides the preparation method of described a kind of control released gastrodin preparation single-layer sheet,
The method comprises the following steps
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into immediate-release granules;
(2) gastrodine II and dispersant are disperseed, add diluent, be prepared into release pills, use macromolecular material, antiplastering aid, lubricant to wrap up piller, be prepared into slow-release micro-pill;
(3) by after the slow-release micro-pill mix homogeneously of the immediate-release granules of the above-mentioned gastrodine I making and gastrodine II, add lubricant, use tablet machine tabletting, obtain control released gastrodin preparation single-layer sheet.
The invention provides the preparation method of described a kind of control released gastrodin preparation double-layer tablet,
The method comprises the following steps:
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into granule, then add lubricant, be prepared into release layer granule;
(2) gastrodine II and dispersant are disperseed, add diluent to be prepared into granule, then add macromolecular material, antiplastering aid and lubricant to be prepared into slow release layer micropill;
(3) by the slow release layer micropill of the release layer granule of the above-mentioned gastrodine I making and gastrodine II, use tablet machine compacting, obtain control released gastrodin preparation double-layer tablet.
The invention provides the preparation method of described a kind of control released gastrodin preparation capsule,
The method comprises the following steps:
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into immediate-release granules;
(2) gastrodine II and dispersant disperse, and add diluent to be prepared into granule, then add macromolecular material, antiplastering aid and lubricant to be prepared into slow-release micro-pill;
(3) by the slow-release micro-pill of the immediate-release granules of the above-mentioned gastrodine I making and gastrodine II, use capsule machine to carry out two step fills: first in capsule shells, pour into the immediate-release granules of gastrodine I, and then the slow-release micro-pill that pours into gastrodine II to be made capsule; Or by directly filling with into capsule after the slow-release micro-pill mix homogeneously of the immediate-release granules of gastrodine I and gastrodine II, obtain control released gastrodin preparation capsule.
The method that described in the inventive method, gastrodine disperses, comprises solwution method, fusion method and solid dispersion method.Solwution method is that gastrodine is directly dispersed or dissolved in dispersant.Fusion method is that gastrodine is dispersed in the dispersant of melting.Solid dispersion method is to utilize pulverizer or grinder that gastrodine and dispersant are carried out to common pulverizing or grind altogether the object that reaches dispersion.
The method that the dispersion of gastrodine described in the inventive method is further prepared into granule or micropill comprises homogenizer granulation, fluidized bed granulation method, extrudes spheronization, centrifugal granulation and dry method roll shaft pressing plate are pulverized granulation.
Control released gastrodin preparation of the present invention, after taking, discharges rapidly the medicine of certain predose, onset rapidly in the early stage.Then continue in vivo slowly to discharge remaining medicine, maintain effective blood drug level of long period.Because product of the present invention has adopted special rapid release technology at the release initial stage, accelerated onset time, improved bioavailability, reach the object of quick acting; In release, adopt slow release method mid-term to latter stage, maintained release amount of medicine stably, maintained blood drug level stably, improved the therapeutic effect of medicine, reduced toxic and side effects.
Product of the present invention is a kind of special delivery formulations, and 10 minutes initial stages burst size that gastrodine discharges at product reaches 30%-50%, and the gastrodine of residue 50%-70% carries out slowly release again and maintains 12-20 hour.In addition, during product of the present invention is tested in vitro, show that its burst size at the initial stage of release is not subject to the impact of pH value and mixing speed, slowly the release mode of release portion maintains zero level or first-order release pattern.
The inventor is according to the dissolution detection method of biological digestion instrument, simulating fasted conditions at pH1.2 dissolution medium respectively, under 20dpm condition, carry out stripping experiment 2 hours, then forward pH6.8 dissolution medium to, under 20dpm condition, carry out stripping experiment 18 hours and after meal condition at pH4.5 dissolution medium, under 40dpm condition, carry out stripping experiment 4 hours, then forward pH6.8 dissolution medium to, under 20dpm condition, carry out stripping experiment 16 hours.
Stripping burst size scope is all as follows:
Within 10 minutes, burst size 30% to 50%
Within 1 hour, burst size 30% to 60%
Within 8 hours, burst size 60% to 90%
Within 16 hours, burst size is more than 85%.
In fasting condition and take this product to 8 health volunteers under condition after meal on an empty stomach, the biological utilisation degrees of data in body is as follows respectively:
| Fasting is condition on an empty stomach | Condition after meal | |
| C max（ug/ml） | 435±143 | 456±184 |
| AUC 0→t | 5161.75±736.06 | 5012.12±949.80 |
Control released gastrodin preparation of the present invention release in vivo absorbs the impact of pH value and food in receptor not, has guaranteed at the Different therapeutical effect of the lower product of Different Individual and different condition less.
Control released gastrodin preparation of the present invention is from patient's clinical application demand, be designed to special delivery formulations, the releasing mechanism that more meets clinical application demand, embodied the combination of pharmaceutical preparation and clinical application, in the R and D of widening medicine, be significant, have great using value and market value.
Accompanying drawing explanation
The biological digestion instrument release profiles of accompanying drawing 1 embodiment 1
Vertical coordinate: burst size %, abscissa: the time (hour, minute)
Plasma concentration curve in accompanying drawing 2 bodies
In figure, rhombus represents the interior plasma concentration curve of body of embodiment 4
Plasma concentration curve in the body of square expression ordinary preparation
Triangle represents plasma concentration curve in general slow releasing preparation body
The specific embodiment
Raw materials used commercially available the obtaining of following examples.
Embodiment 1
Formula:
Preparation:
(1) immediate release section: by the melting under 65 ℃ of conditions of 300 grams of Macrogol 4000s, 30 grams of gastrodine I and 24 grams of polyvinylpolypyrrolidone are added in the Macrogol 4000 of melting, stir while adding, and holding temperature stirs 10 minutes, mixture is cooled to room temperature (25 ℃).With ZSJE type blade type pulverizer, cooling mixture was beaten to the screen cloth of 1.0mm under 5000rpm condition.To sieve material, 160 grams of microcrystalline Cellulose and 80 grams of pregelatinized Starch mix 10 minutes in DGN V-Mixer, add 6 grams of sodium stearyl fumarates to mix and within 5 minutes, obtain 600 grams of final hybrid particles of immediate release section.
(2) slow-released part, by the melting under 80 ℃ of conditions of 35 grams of Glyceryl Behenates, 70 grams of gastrodine II add in the Glyceryl Behenate of melting, stir while adding, and holding temperature stir 10 minutes, and mixture is cooled to room temperature (25 ℃).With blade type pulverizer, cooling mixture is crossed to the screen cloth of 1.0mm under 5000rpm condition.To sieve material, 70 grams of lactose and 120 grams of hypromellose K100LV mix 10 minutes in mixer, add 5 grams of sodium stearyl fumarates to mix and within 5 minutes, obtain 300 grams of slow-release micro-pill.
By 600 milligrams of final hybrid particles of immediate release section and 300 milligrams of slow-release micro-pill, use Fitow 102i double-layer tablet tablet machine to press 1000 of double-layer tablet, every 900 milligrams.Machine pressure 10KN, tablet hardness 120N.
Embodiment 2:
Formula:
Preparation:
(1) 480 grams of gastrodine I, 48 grams of polyoxyethylene sorbitan monoleates and certain water gaging are prepared into solution, 141 grams of microcrystalline Cellulose are added in above-mentioned solution, stir while adding, form stable jelly, drying under reduced pressure at 50 ℃, remove moisture, with blade type pulverizer, by being dried mixture, under 5000rpm condition, cross the screen cloth of 2.0mm, make immediate-release granules.
(2) 320 grams of gastrodine II and 32 grams of hyprolose are mixed with to the aqueous solution of 30% solid content, use fluid bed GPCG2 to add medicine on 200 grams of microcrystalline Cellulose pillers this solution, obtain the piller of adding medicine to, the acetone aqueous isopropanol that re-uses 120 grams of polyvinyl acetate carries out coating to medicine-feeding piller, makes slow-release micro-pill.
(3) immediate-release granules, slow-release micro-pill, 120 grams of microcrystalline Cellulose and 30 grams of carboxymethyl starch sodium are mixed 10 minutes in mixer, add again 9 grams of magnesium stearate to mix 3 minutes, make final mixture, use ZP-7 type tablet machine to carry out tabletting, 1000 of tabletting amounts, every 1500 milligrams.Machine pressure 10KN, tablet hardness 130N.
Embodiment 3:
Formula:
Preparation:
(1) will after 120 grams of gastrodine I and 120 grams of PVP K30 mix homogeneously, with jet mill, pulverize altogether; the granularity 90% of having pulverized is below 20um; use a small amount of water that this common powder compounds, 120 grams of microcrystalline Cellulose and 45 grams of cross-linking sodium carboxymethyl celluloses are granulated in SHK-4B high speed wet granulation machine, 50 ℃ dry after 2 hours and 5 grams of sodium lauryl sulphates be mixed and made into 410 grams of immediate-release granules.
(2) 180 grams of gastrodine II, 150 grams of microcrystalline Cellulose and 60 grams of hypromellose E6 are prepared into wet stock with a certain amount of water with high speed wet granulation machine; with extruding spheronizator, be prepared into pastille piller; particle size distribution is at 400-1000 micron; 90 grams of ethyl celluloses and 10 grams of Pulvis Talci are made into 8% acetone isopropyl alcohol suspension; piller is carried out to coating, be prepared into 490 grams of slow-release micro-pill.
With capsule filling machine IN-CAP XL, the immediate-release granules of 410 grams is become to capsule, 1000 of fill amounts, 900 milligrams every with fill after the slow-release micro-pill mix homogeneously of 490 grams.
Embodiment 4:
Formula:
Preparation:
(1) 300 grams of gastrodine I of immediate release section and 50 grams of polyoxyethylene hydrogenated Oleum Ricini dissolvings are dispersed in 50 grams of water; the mix homogeneously in High Speed Stirring Machine by 130 grams of microcrystalline Cellulose and 15 grams of cross-linking sodium carboxymethyl celluloses; add above-mentioned aqueous solution to granulate; after granulation completes, adding 5 grams of sodium lauryl sulphates stirrings, after 1 minute, mixture is put into 40 ℃ of baking ovens is dried; be dried 16 mesh sieves, be prepared into 500 milligrams of immediate-release granules.
Press slow-released part prescription, by the melting under 80 ℃ of conditions of 46 grams of Glyceryl Behenates, 300 grams of gastrodine II and 80 grams of HPMC K4Ms are added in the Glyceryl Behenate of melting, stir while adding, and holding temperature stirs 10 minutes, mixture is cooled to room temperature (25 ℃).With blade type pulverizer, cooling mixture is crossed to the screen cloth of 2.0mm under 3800rpm condition.Material and the 5 grams of magnesium stearate of sieving are mixed and within 5 minutes, are obtained slow-release micro-pill.
Use double-layer tablet tablet machine to press double-layer tablet, 1000 of tabletting amounts, every 930 milligrams 500 milligrams of immediate-release granules and 430 milligrams of slow-release micro-pill final mixtures.Machine pressure 16KN, tablet hardness 150N.
Embodiment 5:
According to the dissolution detection method of biological digestion instrument, leaching condition by the tablet of embodiment 4 preparations under simulation fasted conditions, at pH1.2 dissolution medium, carries out stripping experiment 2 hours under 20dpm condition, then forward pH6.8 dissolution medium to, under 20dpm condition, carry out stripping experiment 18 hours.
Stripping burst size is as follows:
Within 10 minutes, discharge 45%
Within 1 hour, discharge 53%
Within 8 hours, discharge 78%
Within 16 hours, discharge 95%.
Result shows: tablet discharged and reaches 45% fast at 10 minutes, and maintains certain rate of release and reach 16 hours, presents special release mode.
Embodiment 6:
According to the dissolution detection method of biological digestion instrument, the tablet of embodiment 4 preparation, at the leaching condition of simulating under condition after meal, at pH4.5 dissolution medium, is carried out to stripping experiment 4 hours under 40dpm condition, then forward pH6.8 dissolution medium to, under 20dpm condition, carry out stripping experiment 16 hours.
Stripping burst size is as follows:
Within 10 minutes, discharge 50%
Within 1 hour, discharge 58%
Within 8 hours, discharge 81%
Within 16 hours, discharge 93%.
Result shows: tablet discharged and reaches 50% fast at 10 minutes, and maintains certain rate of release and reach 16 hours, presents special release mode, and extremely similar with the release of embodiment 5, and in vitro in simulation experiment, before or after meals release difference is minimum.
Claims (10)
1. a control released gastrodin preparation, is characterized in that, described control released gastrodin preparation is comprised of immediate release section and slow-released part; The gastrodine I of described immediate release section accounts for the 30%-60% of gastrodine total amount in controlled release preparation; Slow-released part gastrodine II accounts for the 40%-70% of gastrodine total amount in controlled release preparation.
2. a control released gastrodin preparation, is characterized in that, described control released gastrodin preparation is comprised of immediate release section and slow-released part; The gastrodine I of described immediate release section accounts for the 40%-50% of gastrodine total amount in controlled release preparation; Slow-released part gastrodine II accounts for the 50%-60% of gastrodine total amount in controlled release preparation.
3. control released gastrodin preparation according to claim 1 and 2, is characterized in that, its single-dose preparations is containing gastrodine 100-800mg.
4. control released gastrodin preparation according to claim 3, is characterized in that, its single-dose preparations is containing gastrodine 300-600mg.
5. control released gastrodin preparation according to claim 1 and 2, is characterized in that, described immediate release section is comprised of gastrodine I and the pharmaceutical carrier as active component; Described pharmaceutical carrier comprises diluent, disintegrating agent, lubricant and dispersant; Described diluent is selected from one or more in microcrystalline Cellulose, starch, mannitol, sorbitol or lactose; Disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose or carboxymethyl starch sodium; Lubricant is selected from one or more in magnesium stearate, stearic acid, polyethylene glycol 6000, sodium lauryl sulphate or sodium stearyl fumarate; Dispersant is selected from one or more in polyvidone, hypromellose, hyprolose, Polyethylene Glycol, Polysorbate or polyoxyethylene hydrogenated Oleum Ricini; The weight proportion of described gastrodine I and disintegrating agent is 20:1-1.25:1, preferably 10:1-2.5:1; The weight proportion of gastrodine I and dispersant is 1:10-10:1, preferably 1:3-6:1; The weight proportion of gastrodine I and diluent is 1:8-3.5:1; The weight proportion of gastrodine I and lubricant is 5:1-75:1.
6. control released gastrodin preparation according to claim 1 and 2, is characterized in that, described slow-released part is comprised of gastrodine II and the pharmaceutical carrier as active component; Described pharmaceutical carrier comprises diluent, lubricant, antiplastering aid, dispersant and macromolecular material; Described diluent is selected from one or more in microcrystalline Cellulose, starch, mannitol, sorbitol or lactose; Lubricant is selected from one or more in magnesium stearate, stearic acid, polyethylene glycol 6000, sodium lauryl sulphate or sodium stearyl fumarate.Antiplastering aid is selected from one or more in Pulvis Talci or glyceryl monostearate; Dispersant is selected from one or more in polyvidone, hypromellose, hyprolose, Polyethylene Glycol, Glyceryl Behenate, Polysorbate or polyoxyethylene hydrogenated Oleum Ricini; Macromolecular material is selected from one or more in polyvinyl acetate, ethyl cellulose, polyacrylic resin, cellulose acetate, hypromellose, hyprolose, polyoxyethylene or sodium alginate.The weight proportion of described gastrodine II and disintegrating agent is 1:10-10:1, preferably 1:3-6:1; The weight proportion of gastrodine II and macromolecular material is 1:5-10:1, preferably 1:2-7:1; The weight proportion of gastrodine II and diluent is 1:8-3.5:1; The weight proportion of gastrodine II and lubricant is 5:1-75:1.
7. control released gastrodin preparation according to claim 1 and 2, is characterized in that, described controlled release preparation is single-layer sheet, double-layer tablet or capsule.
8. a preparation method for control released gastrodin preparation as claimed in claim 1 or 2, is characterized in that, the method comprises the following steps
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into immediate-release granules;
(2) gastrodine II and dispersant are disperseed, add diluent, be prepared into release pills, use macromolecular material, antiplastering aid, lubricant to wrap up piller, be prepared into slow-release micro-pill
(3) by after the slow-release micro-pill mix homogeneously of the immediate-release granules of the above-mentioned gastrodine I making and gastrodine II, add lubricant, use tablet machine tabletting, then at sheet coated outside film coating, obtain control released gastrodin preparation single-layer sheet.
9. a preparation method for control released gastrodin preparation as claimed in claim 1 or 2, is characterized in that, the method comprises the following steps:
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into granule, then add lubricant, be prepared into release layer granule;
(2) gastrodine II and dispersant are disperseed, add diluent to be prepared into granule, then add macromolecular material, antiplastering aid and lubricant to be prepared into slow release layer micropill;
(3) by the slow release layer micropill of the release layer granule of the above-mentioned gastrodine I making and gastrodine II, use tablet machine compacting, obtain control released gastrodin preparation double-layer tablet.
10. a preparation method for control released gastrodin preparation as claimed in claim 1 or 2, is characterized in that, the method comprises the following steps:
(1) gastrodine I and dispersant are disperseed, add diluent and disintegrating agent, be prepared into immediate-release granules;
(2) gastrodine II and dispersant disperse, and add diluent to be prepared into granule, then add macromolecular material, antiplastering aid and lubricant to be prepared into slow-release micro-pill;
(3) by the slow-release micro-pill of the immediate-release granules of the above-mentioned gastrodine I making and gastrodine II, use capsule machine to carry out two step fills: first in capsule shells, pour into the immediate-release granules of gastrodine I, and then the slow-release micro-pill that pours into gastrodine II to be made capsule; Or by directly filling with into capsule after the slow-release micro-pill mix homogeneously of the immediate-release granules of gastrodine I and gastrodine II, obtain control released gastrodin preparation capsule.
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| CN201210335155.1A Pending CN103655585A (en) | 2012-09-11 | 2012-09-11 | Gastrodin controlled release preparation and preparation method thereof |
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| CN109771392A (en) * | 2019-04-09 | 2019-05-21 | 湖南素元生物科技有限公司 | Rhizoma Gastrodiae sustained release pellet and its supersonically preparation method |
| CN109793722A (en) * | 2019-04-02 | 2019-05-24 | 生态环境部南京环境科学研究所 | A kind of preparation method of Rhizoma Gastrodiae sustained release pellet |
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| CN109793722A (en) * | 2019-04-02 | 2019-05-24 | 生态环境部南京环境科学研究所 | A kind of preparation method of Rhizoma Gastrodiae sustained release pellet |
| CN109771392A (en) * | 2019-04-09 | 2019-05-21 | 湖南素元生物科技有限公司 | Rhizoma Gastrodiae sustained release pellet and its supersonically preparation method |
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