CN103599141A - Ginkgo leaf total flavone controlled-release tablet and preparation method thereof - Google Patents
Ginkgo leaf total flavone controlled-release tablet and preparation method thereof Download PDFInfo
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- CN103599141A CN103599141A CN201310579576.3A CN201310579576A CN103599141A CN 103599141 A CN103599141 A CN 103599141A CN 201310579576 A CN201310579576 A CN 201310579576A CN 103599141 A CN103599141 A CN 103599141A
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- polyoxyethylene
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Abstract
The invention belongs to the technical field of medicines, and particularly discloses a ginkgo leaf total flavone controlled-release tablet and a preparation method thereof. The controlled-release tablet disclosed by the invention is a tablet which is prepared by combining polyoxyethylene and a controlled-release skeleton material and adopting a conventional tablet preparation technology and has the zero-order release behavior characteristic. The controlled-release tablet consists of an active ingredient ginkgo leaf total flavone, a high polymer material polyoxyethylene (PEO), the controlled-release skeleton material and a certain amount of release rate conditioning agent. The active ingredients of the ginkgo leaf total flavone mainly comprise isorhamnetin, kaempferide and quercetin, and the total flavonoid glycoside content of the quercetin is not lower than 20%. Compared with a common tablet, the ginkgo leaf total flavone controlled-release tablet has the advantages that the controlled-release tablet can be used for maintaining the constancy of the blood concentration, reducing the adverse reactions of the medicines and improving the compliance of the patients. The preparation method is simple in technological operation, low in cost, easy to control and suitable for industrial large-scale production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of Folium Ginkgo total flavones controlled release tablet and preparation method.
Background technology
Folium Ginkgo total flavones is Folium Ginkgo extract, and content is more than 20%, mainly contains some flavone and flavonoid glycoside composition, comprises the compositions such as Quercetin, isorhamnetin, kaempferide class.Study of pharmacy shows, in Folium Ginkgo, total flavones can increase cerebrovascular flow, improves cerebrovascular circulatory function, protection brain cell, and coronary artery dilator, prevents angina pectoris and myocardial infarction, prevents thrombosis, improves body immunity.Very useful per capita to coronary heart diseases and angina pectoris, cerebral arteriosclerosis, alzheimer disease, hypertension.
Existingly in the market take the Chinese patent medicine preparation that Folium Ginkgo total flavones is crude drug, comprise tablet, capsule, injection, drop, oral liquid, pill and ointment etc., be ordinary preparation.As conventional tablet, every composition containing ginkgo leaf flavonoids 9.6mg, oral 1-2 pieces/times, three times on the one.Compliance is poor, and blood concentration fluctuation is large, and long term administration easily causes untoward reaction.
For addressing the above problem, existing researcher has been developed Folium Ginkgo extract controlled release tablet, described patent CN1177603C, this sheet is film controlling type controlled release tablet, utilize packaging technique to delay medicine in the gastrointestinal holdup time, drug slow is absorbed lastingly, at 2-12 hours, present zero level and discharge.But this controlled release tablet coating is comparatively loaded down with trivial details, and coating solvent is organic solvent, unfavorable to health.
Summary of the invention
The object of the present invention is to provide that a kind of controlled-release effect is good, the simple Folium Ginkgo total flavones controlled release tablet of preparation technology.Good, the applicable large-scale production of this sheet controlled-release effect, to overcome the shortcoming and defect in existing medicine and technology.
Another object of the present invention is to provide the preparation method of Folium Ginkgo total flavones controlled release tablet.
The present invention adopts traditional slow releasing tablet technique, adopts the method for direct compression or wet granule compression tablet, uses polyoxyethylene and conventional slow-release material, by suitable proportioning, prepares the controlled release tablet with zero level releasing effect.When polyoxyethylated molecular weight be greater than or etc. 2,000,000 o'clock, in prescription, need to add framework material to carry out adjustment release speed; When polyoxyethylated molecular weight is less than 2,000,000 o'clock, can prepare controlled release tablet by adding suitable framework material or not adding framework material, concrete proportioning is: polyoxyethylene: framework material is 1:0.1-1:15.This controlled release tablet is compared with traditional slow releasing tablet, has the advantages that zero level discharges.It is slow, non-constant speed that tradition slow releasing tablet discharges, result medicine in vivo the release ratio later stage in early stage fast, cause in body blood drug level unstable; And zero level release is constant speed, medicine release constant speed is in vivo even, has effectively avoided the peak valley phenomenon of ordinary preparation and slow releasing preparation blood drug level; Reduce medicining times and untoward reaction, improved patient's compliance.And said preparation is compared with traditional controlled releasing penetrant pump, there is identical zero-order release behavior, but saved the operations such as osmotic pump preparation coating, punching, this has greatly saved industrialized cost.
Therefore this invention has been drawn the advantage of traditional slow releasing preparation and controlled releasing penetrant pump: adopt the preparation technology of traditional slow releasing preparation, prepare the controlled release tablet with the zero-order release behavior identical with osmotic pumps.
Folium Ginkgo total flavones controlled release tablet provided by the invention, its composition and percetage by weight are:
Folium Ginkgo total flavones 20%--65%
Polyoxyethylene PEO 8%--30%
Filler 10%--50%
Lubricant 0.5%--3%.
Wherein polyoxyethylene PEO is preferably 8%--25%;
Framework material is 10%-25%;
The preferred prescription percentage by weight of the present invention is:
Folium Ginkgo total flavones 45%--55%
Polyoxyethylene PEO 8%--25%
Filler 15%--30%
Lubricant 0.5%--2%
Described framework material is conventional slow-release material, is selected from one or more in hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, Hydroxylated acrylic resin class, carbomer, stearic acid, glyceryl monostearate, castor oil hydrogenated, Cera Flava, paraffin, white beeswax, microwax.Preferred hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, carbomer, paraffin.
Described polyoxyethylene is that molecular weight is at 1,000,000-7, between 000,000, preferred PEO N12K(molecular weight, 1,000,000), PEO N60K, (molecular weight, 2,000,000), WSR 301(molecular weight, 4,000,000), WSR Coagulant(molecular weight, 5,000,000), WSR 303(molecular weight, 7,000,000) one or more in.When polyoxyethylated molecular weight be greater than or etc. 2,000,000 o'clock, in prescription, need framework material to carry out adjustment release speed; When polyoxyethylated molecular weight is less than 2,000,000 o'clock, can be by adding suitable framework material Huo Bu Calais to prepare controlled release tablet, concrete proportioning is: polyoxyethylene: framework material is 1:0.2-1:15, preferably 1:1-1:10.
The preparation method of above-mentioned Folium Ginkgo total flavones controlled release tablet provided by the invention can have following two kinds:
1, wet method tabletting
Get polyoxyethylene PEO, framework material, Folium Ginkgo total flavones, filler and mix, add adhesive, soft material processed, sieves, wet granular processed, and dry, granulate, adds lubricant to mix, and tabletting makes Folium Ginkgo total flavones controlled release tablet.Described binding agent is the alcoholic solution of variable concentrations.
2, direct powder compression
Get by weight percentage polyoxyethylene PEO, framework material, Folium Ginkgo total flavones and filler, mix, add lubricant, tabletting, makes composition containing ginkgo leaf flavonoids controlled release tablet.
Polyoxyethylene (PEO) is a kind of pharmaceutic adjuvant of domestic and international extensive use, has that compressibility is good, Drug loading capacity is strong and the Release Properties advantage such as be not subject to that PH affects, and is epochmaking hydrophilic support material in controlled release preparation.The present invention is prepared into hydrophilic gel controlled release tablet with polyoxyethylene.Polyoxyethylene absorbs water and expands rapidly in water, forms viscosity gel layer, the release of blocking medicine.Simple with polyoxyethylene, if the release medicine that low viscous polyoxyethylene can constant speed, and can reach release requirement; But use viscosity larger, medicine only depend on diffusion from sheet out, rate of release is very slow, need to add the water wetted material that some viscosity are little to carry out adjustment release speed.The material viscosity such as HPMC are little, form rapidly duct after water suction, and medicine slowly discharges from duct, thereby reaches the effect of controlled release.If use separately polyoxyethylene, drug release is slow and solution is more glutinous, is unfavorable for detecting.When adopting slow-release material and PEO coupling, can reach controlled-release function, and can overcome the gel that PEO forms very fragile, be easy to the shortcomings such as corrosion, smaller volume, viscosity are larger.
Accompanying drawing explanation
Fig. 1 is total flavones release profiles in Folium Ginkgo total flavones sustained-release preparation;
The specific embodiment
Further understand by the following specific embodiments the present invention.But they are not limitations of the present invention
Embodiment 1
Prescription:
Folium Ginkgo total flavones 200mg
PEO-301 145mg
Methylcellulose 50mg
Lactose 90mg
Magnesium stearate 2mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, methylcellulose, lactose are crossed respectively to 80 mesh sieves (must first grind if desired), take each adjuvant mix and mix with Folium Ginkgo total flavones by recipe quantity, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.9904.
Prescription:
Folium Ginkgo total flavones 200mg
PEO-N10 70mg
Ka Baimu 130mg
Microcrystalline Cellulose 80mg
Magnesium stearate 4mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, Ka Baimu, microcrystalline Cellulose are crossed respectively to 80 mesh sieves (must first grind if desired), by recipe quantity, take each adjuvant and Folium Ginkgo total flavones, by the equivalent method of progressively increasing, mix, then adding dehydrated alcohol granulates, under 45 ℃ of conditions, dry 12 hours, add magnesium stearate and mix, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.980.
Embodiment 3
Prescription:
Folium Ginkgo total flavones 200mg
PEO–N60K 90mg
Hydroxypropyl cellulose 60mg
Microcrystalline Cellulose 80mg
Magnesium stearate 2mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, hydroxypropyl cellulose, microcrystalline Cellulose are crossed respectively to 80 mesh sieves (must first grind if desired), by recipe quantity, take each adjuvant and Folium Ginkgo total flavones, by the equivalent method of progressively increasing, mix, then add 90% alcohol granulation, under 45 ℃ of conditions, dry 12 hours, add magnesium stearate and mix, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.985.
Prescription:
Folium Ginkgo total flavones 200mg
PEO WSR Coagulant 44mg
HPMC-4M 76mg
Micropowder silica gel 80mg
Magnesium stearate 4mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, HPMC, micropowder silica gel are crossed respectively to 80 mesh sieves (must first grind if desired), by recipe quantity, take each adjuvant and Folium Ginkgo total flavones, by the equivalent method of progressively increasing, mix, then add 65% alcohol granulation, under 45 ℃ of conditions, dry 12 hours, add magnesium stearate and mix, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.9823.
Embodiment 5
Prescription:
Folium Ginkgo total flavones 250mg
PEO-303 80mg
Paraffin 60mg
Starch 80mg
Magnesium stearate 8mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, paraffin, starch are crossed respectively to 80 mesh sieves (must first grind if desired), by recipe quantity, take each adjuvant and Folium Ginkgo total flavones, by the equivalent method of progressively increasing, mix, then add 90% alcohol granulation, under 45 ℃ of conditions, dry 12 hours, add magnesium stearate and mix, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.9767.
Prescription:
Folium Ginkgo total flavones 200mg
PEO -301 68mg
HPMC-4M 52mg
Microcrystalline Cellulose 80mg
Magnesium stearate 4mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, HPMC, microcrystalline Cellulose are crossed respectively to 80 mesh sieves (must first grind if desired), take each adjuvant mix and mix with Folium Ginkgo total flavones by recipe quantity, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.998, approaches very much zero level and discharges.
Embodiment 7
Prescription:
Folium Ginkgo total flavones 200mg
PEO-301 50mg
HPMC-100M 100mg
Microcrystalline Cellulose 80mg
Magnesium stearate 4mg
Method for making:
Folium Ginkgo total flavones and polyoxyethylene, HPMC, microcrystalline Cellulose are crossed respectively to 80 mesh sieves (must first grind if desired), take each adjuvant mix and mix with Folium Ginkgo total flavones by recipe quantity, tabletting, obtains.
By release in vitro curve, recording correlation coefficient r is 0.9836.
In order to compare with Folium Ginkgo total flavones controlled release tablet, this research has simultaneously also been prepared Folium Ginkgo total flavones double-layer osmotic pump controlled-release tablet, and take the conventional silver Folium Pruni total flavone sustained-release tablet that hydroxypropyl methylcellulose is prepared into as framework material, and preparation method is as follows:
Folium Ginkgo total flavones double-layer osmotic pump controlled-release tablet
Core formulation:
Medicated layer
Folium Ginkgo total flavones 200mg
Sodium chloride 30mg
PEO N10 20mg
Magnesium stearate 2mg
Boosting layer
PEO WSR303 100mg
Sodium chloride 30mg
Magnesium stearate 2mg
Coating membrane prescription:
Cellulose acetate 30g
Polyethylene Glycol 2g
Dissolve the solvent prescription of coating membrane material
Acetone 1000ml
Distilled water 9ml
Preparation technology:
Recipe quantity medicine and adjuvant are all crossed to 80 mesh sieves, and medicine layer prescription and boosting layer prescription be mix homogeneously respectively, and employing direct powder compression, carries out precompressed to medicine layer, and then adds boosting lamination and make double layer osmotic pump label.Cellulose acetate and Polyethylene Glycol are dissolved in respectively to mix homogeneously in acetone and distilled water, with coating pan, label are carried out to coating, weightening finish is 10%, after coating in baking oven 40 ℃ solidify 12 hours.Then at coated tablet medicated layer one side power auger, prepare the small delivery aperture of a 0.6mm diameter, be Folium Ginkgo total flavones double-layer osmotic pump controlled-release tablet.
Traditional Folium Ginkgo total flavones slow releasing tablet
Folium Ginkgo total flavones 200 mg
Low-substituted hydroxypropyl cellulose 20mg
CMC-NA 13mg
MCC 75mg
Preparation technology:
Supplementary material is crossed respectively to 80 object sieves, take the Folium Ginkgo total flavones of recipe quantity, HPMC K4M, low-substituted hydroxypropyl cellulose, MCC, CMC-NA adopts the equivalent method of progressively increasing to mix except lubricant, mixes, and then adds dehydrated alcohol and granulates, under 45 ℃ of conditions, dry 12 hours, add magnesium stearate and mix, tabletting, obtains.
the research of Folium Ginkgo total flavones controlled release tablet vitro release
According to two appendix XD drug release determination first methods of Chinese Pharmacopoeia version in 2010,0.5%SDS solution 900 mL of take are medium, rotating speed is 100r/min, temperature is (37 ± 0.5) ℃, timing sampling 5ml, through microporous filter membrane (0.45 μ m), filter, supplement the SDS solution of same volume synthermal 0.5% simultaneously.Ultraviolet method is measured the absorbance of Folium Ginkgo total flavones, calculates Cumulative release amount.
Release profiles, as Fig. 1, by the release in vitro curve comparison of several preparations, can significantly be found out, Folium Ginkgo total flavones controlled release tablet, and the release in vitro of 0 ~ 14h has all reached zero level release characteristic, correlation coefficient r >0.98.In order to compare with Folium Ginkgo total flavones controlled release tablet, this research has simultaneously also been prepared Folium Ginkgo total flavones double-layer osmotic pump controlled-release tablet and take the conventional silver Folium Pruni total flavone sustained-release tablet that hydroxypropyl methylcellulose is prepared into as framework material, as can be seen from Figure 1, Folium Ginkgo total flavones controlled release tablet tablets in vitro has reached the feature of the zero-order release identical with osmotic pump preparation, and conventional silver Folium Pruni total flavone sustained-release tablet is slow non-constant speed release medicine.Hence one can see that, and the Folium Ginkgo total flavones controlled release tablet of this research invention is compared the feature with external constant speed release medicine with traditional preparation, and preparation technology is simple simultaneously, can reduce production costs, and is convenient to the advantages such as suitability for industrialized production.
Claims (10)
1. a Folium Ginkgo total flavones controlled release tablet, is characterized in that, comprises following composition and percetage by weight to be:
Folium Ginkgo total flavones 20%--65%
Polyoxyethylene PEO 8%--30%
Framework material 10%--30%
Filler 10%--50%
Lubricant 0.5%--3%.
2. Folium Ginkgo total flavones controlled release tablet according to claim 1, is characterized in that, polyoxyethylene PEO is 8%--25%.
3. Folium Ginkgo total flavones controlled release tablet according to claim 1, is characterized in that, framework material is 10%-25%.
4. Folium Ginkgo total flavones controlled release tablet according to claim 1, is characterized in that polyoxyethylene: framework material is 1:0.1-1:15, preferably 1:1-1:10.
5. the Folium Ginkgo total flavones controlled release tablet described in any one according to claim 1-4, it is characterized in that, described framework material is selected from one or more in hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, Hydroxylated acrylic resin class, carbomer, stearic acid, glyceryl monostearate, castor oil hydrogenated, Cera Flava, paraffin, white beeswax, microwax.
6. the Folium Ginkgo total flavones controlled release tablet described in any one according to claim 1-4, is characterized in that described polyoxyethylene is one or more of polyoxyethylene 301, polyoxyethylene 303, polyoxyethylene N80, polyoxyethylene N10.
7. the Folium Ginkgo total flavones controlled release tablet described in any one according to claim 1-4, it is characterized in that described filler is one or more in microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate, amylum pregelatinisatum, lactose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, described lubricant is the one or more combination in magnesium stearate, Pulvis Talci, magnesium laurylsulfate, micropowder silica gel, hydrogenated vegetable oil, Polyethylene Glycol.
8. the Folium Ginkgo total flavones controlled release tablet described in any one according to claim 1-7, is characterized in that, the main component of Folium Ginkgo total flavones is isorhamnetin, kaempferide, Quercetin, and its total amount is more than 20%.
9. a preparation method for Folium Ginkgo total flavones controlled release tablet as claimed in claim 1, is characterized in that:
Get polyoxyethylene, framework material, Folium Ginkgo total flavones, filler, cross 80 object sieves respectively, by prescription, take above each composition, adopt the equivalent method of progressively increasing to mix, add adhesive, soft material processed, crosses 18 mesh sieves, and wet granular processed is dry, granulate, adds lubricant and mixes, tabletting;
Or get polyoxyethylene, framework material, Folium Ginkgo total flavones, filler, lubricant and cross respectively 80 mesh sieves, by prescription, take above each composition, by the equivalent method of progressively increasing, mix, tabletting, obtains.
10. preparation method according to claim 9, is characterized in that, the alcoholic solution that described adhesive is variable concentrations.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103191432A (en) * | 2013-04-27 | 2013-07-10 | 中国药科大学 | Water-soluble medicine framework sustained release tablet and preparation method thereof |
| CN103372034A (en) * | 2012-04-19 | 2013-10-30 | 王颖 | Preparation method of ginkgo biloba extract |
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- 2013-11-19 CN CN201310579576.3A patent/CN103599141A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103372034A (en) * | 2012-04-19 | 2013-10-30 | 王颖 | Preparation method of ginkgo biloba extract |
| CN103191432A (en) * | 2013-04-27 | 2013-07-10 | 中国药科大学 | Water-soluble medicine framework sustained release tablet and preparation method thereof |
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Application publication date: 20140226 |
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