CN101623269A - Oral sustained release granules - Google Patents
Oral sustained release granules Download PDFInfo
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- CN101623269A CN101623269A CN200910181933A CN200910181933A CN101623269A CN 101623269 A CN101623269 A CN 101623269A CN 200910181933 A CN200910181933 A CN 200910181933A CN 200910181933 A CN200910181933 A CN 200910181933A CN 101623269 A CN101623269 A CN 101623269A
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Abstract
The invention relates to oral sustained release granules using microcrystalline cellulose and ethyl cellulose as a carrier to be combined with active compositions. The invention solves the problem that the prior granule coating type sustained release insoluble drug is too slow in releasing from a skeleton, the release of the drug is affected by pH values and digestive hydrolysis speed, coating needs to be processed by special coating equipment which is expensive, has complex process, high requirement of operation and high rate of products with bad quality and is unfavorable to mass industrial production, and the like. In the invention, the microcrystalline cellulose and ethyl cellulose are combined to form a carrier and are matched with active compositions; the microcrystalline cellulose can accelerate the speed of the drug dissolving in a human body, while the ethyl cellulose can sustain the speed the drug dissolved in the human body, so that the absorption of the drug is improved through the cooperation of the microcrystalline cellulose and ethyl cellulose, the bioavailability is improved, the speed of the drug releasing in the human body is controlled, and the active compositions are given full play in the human body.
Description
Technical field
The present invention relates to a kind of slow-releasing granules, particularly a kind of is carrier and the bonded oral sustained release granules of active ingredient with microcrystalline Cellulose and ethyl cellulose.
Background technology
Before this method invention, more about the research of slow-releasing granules aspect, also applied in medicine and the nourishing healthy product simultaneously.At present, the example of the existing preparation method of oral slow-releasing granules preparation is exactly a kind of method with the insoluble macromolecule coating of pastille core material water, though this preparation has the ability of high controlled release drug and excellent moisture resistance, moisture resistance, wearability and storage stability etc., only require consumption quite big usually so that in the medicine very high or particle mean size be control drug release under the situation of 100um or littler microgranule with water solublity by the molecular coating of water-insoluble high score.In addition, increase the coating amount with the situation that delays dissolution rate under, the problem of existence is that the incomplete stripping of medicine can to occur be the phenomenon of the so-called stripping upper limit.
The existing preparation method of another kind of oral slow-releasing granules preparation is with the piller of inert material medicated layer coating, again with this medicated layer lipophilicity compound such as stearic acid and firming agent such as ethyl cellulose coating.Yet the preparation that the method is described is done core material owing to contain piller, so its particle mean size is approximately 1mm or bigger.When producing granule with this big material, the default of granule coating layer takes place in the coating process easily, cause quick disintegrate when oral, this just makes the stripping of its restive medicine, perhaps make it need increase the size of piller, cause oral a large amount of non-active substance of going into, lack practicality when these shortcomings can cause producing granule.
The coating material of granule commonly used has ethyl cellulose, polyethylene kind, crylic acid resin, ethylene-vinyl acetate copolymer etc.The shortcoming of granule coating type slow release has, and the speed that insoluble drug disengages in the skeleton is too slow, and the release of medicine is subjected to pH value, the hydrolysis rate influence of digestive enzyme.So this type drug release is subjected to the gastrointestinal physiologic factor, pH value and peristaltic velocity influence are bigger.And coating will finish with special coating equipment, and this kind equipment comprises fluidized bed coating equipment, centrifugal fluidized bed coating or cooking-pot type coating equipment.This kind equipment costliness, complex process, operation require high, so the defective products rate height of product, and disposable having high input to demanding strict technology of workman, is unfavorable for mass industrialized production.
Summary of the invention
Purpose of the present invention just is to overcome above-mentioned defective, works out a kind of granule of new sustained-release administration, only need simply mix, pelletize, oven dry just can, saved the process of coating.The granular preparation of producing can be controlled the stripping of medicine effectively.
Technical scheme of the present invention is:
Oral sustained release administration granule, its major technique is characterised in that by active ingredient, carrier to be formed, it is 15%～80% that active ingredient accounts for percentage by weight, it is 20～85% that carrier accounts for percentage by weight, wherein carrier is by disintegrating agent or binding agent or combination, and active ingredient is any or multiple combination in resveratrol, Quercetin, anthocyanidin, oligomeric proanthocyanidin, glucosan, flavonoid, tea polyphenols, the vitamin.
The present invention makes granule be stranded in the stomach prolong drug release time, improves drug absorption, is beneficial to the raising bioavailability.Its granule system belongs to a kind of preparation of fluid dynamic equilibrium by medicine and hydrophilic colloid and the prepared oral granular formulation of other auxiliary material.
Particularly, adopt microcrystalline Cellulose (or other disintegrating agents) and ethyl cellulose (EC) to constitute carrier, mate with active ingredient; Microcrystalline Cellulose can quicken medicine dissolution velocity in vivo, and ethyl cellulose can delay medicine dissolution velocity in vivo, by the synergism of the two, just can control medicine rate of release in vivo, make active ingredient in human body, obtain the most effective performance.
Advantage of the present invention and effect also are to provide a kind of method of new slow-releasing granules, and need of coating has not reduced cost, and raw material and equipment are conventional products, easily buying, and technology is simple, and the quality of production is easily controlled, and the yield rate height is suitable for mass industrialized production.
Be in particular in:
1. the composition of granule is beneficial at Entogastric lingering, wherein forms the gel barrier film and expands the original granule shape of maintenance at surface hydration under body temperature behind the bulky grain agent contact gastric juice; And granule discharges medicine earlier under one's belt to reach effective blood drug concentration as early as possible, and bulky grain enters in the intestinal gradually with the food in the stomach, separates the back at enteric and discharges medicine, and effective blood drug concentration is maintained.The test shows of human bioavailability is taken and once can be kept the above time of effective blood drug concentration, thereby reaches a day clothes purpose once.
2. the selection of carrier and consumption can both meet the inside and outside drug release feature that granule requires, and can slowly dissolve diffusion, make effective concentration keep the long period, generally can reach 20～24 hours;
3. pharmaceutically active is strong, and dosage range is big, can make the granule of high medicament contg;
4. applied widely, be not subjected to the gastrointestinal physiologic factor, the influence of pH value and peristaltic velocity; So can carry out sequencing, controlledization of the compatibility of multiple composition and preparation technology etc.;
5. continue to absorb at gastrointestinal tract, as at upper part of small intestine, absorb best B2 etc. and locate to absorb.
Other advantages of the present invention and effect will continue to describe below.
Description of drawings
The external stripping situation sketch map of Fig. 1---embodiments of the invention 1 under the simulated gastric fluid condition.
The external stripping releasing curve diagram of Fig. 2---embodiments of the invention 1 under the simulated gastric fluid condition.
Fig. 3---embodiments of the invention 2 are the releasing curve diagram in 24 hours in simulated gastric fluid.
Fig. 4---embodiments of the invention 3 are the releasing curve diagram in 24 hours in simulated gastric fluid.
Fig. 5---embodiments of the invention 4 are the releasing curve diagram in 24 hours in simulated gastric fluid.
The specific embodiment
Embodiment 1:
Get active ingredient resveratrol, quercetin, anthocyanidin, oligomeric proanthocyanidin, accounting for percentage by weight is 73.75%; Microcrystalline Cellulose is 20% in the carrier, and ethyl cellulose is 5%, polyvinylpyrrolidone 1.5%, and three's sum is 26.5%; The aqueous solution that adds ethanol sieves or extrusion modling with high speed shear mixer mix homogeneously; Make granule after the oven dry.
Embodiment 2:
Get active ingredient resveratrol, quercetin 52.5%; In the carrier ethyl cellulose be 36.7%, polyacrylic resin 10.1%, sum of the two is 46.8%; 0.7% Polyethylene Glycol (PEG400) is dissolved in usefulness high speed shear mixer mix homogeneously in the isopropyl alcohol, sieves or extrusion modling; Make granule after the oven dry.
Embodiment 3:
Get in active ingredient resveratrol, Quercetin, anthocyanidin, oligomeric proanthocyanidin, glucosan, flavonoid, tea polyphenols, the vitamin any or multiple be 40%; Microcrystalline Cellulose is 15% in the carrier, and ethyl cellulose (EC) is 35%, and the aqueous dispersion of ethyl cellulose (trade name Surelease) is 10%, adds aqueous solution with high speed shear mixer mix homogeneously, sieves or is squeezed into molding; Make granule after the oven dry.
Embodiment 4:
Get active ingredient resveratrol, quercetin 16.2%; Microcrystalline Cellulose is 61.8% in the carrier, and the aqueous dispersion of ethyl cellulose is 22.0%, and sum of the two is 83.8%; The aqueous solution that adds ethanol sieves or extrusion modling with high speed shear mixer mix homogeneously; Make granule after the oven dry.
Granule with embodiment 1 is an example: as shown in Figure 1; embodiment 1 particle slow release ability is stronger, its residual logarithm Ln[1-F (t) that treats molten amount] linear with time t, its release equations Ln[1-F (t)]=0.0145-0.1956t r=-0.9973; rate of releasing drug constant K r is 0.1956h
-1, its external stripping meets the first order kinetics process, has reached the slow release control effect of medicine.
As Fig. 2, Fig. 3, shown in Figure 4, the active component resveratrol discharged in simulated gastric fluid in interior 24 hours, and release profiles and release reach in the Chinese Pharmacopoeia requirement to slow-releasing granules.
Experimental results show that according to above, in different active component by add above-mentioned composition be combined into make granule after, discovery can effectively be controlled active component at the intravital rate of release of people, and after finding that active component is through this combination, alleviate the toxic action that active component concentrates release to bring, and, reduced the dose of medicine by continual slow release, increased the effect of medicine.
Detect effect:
1. our employed binding agent and disintegrating agent are the adjuvants that uses in medicine and health product and food through for many years, we can say that it is a safety non-toxic.
2. microcrystalline Cellulose or other disintegrating agents can quicken medicine dissolution velocity in vivo, and binding agent such as ethyl cellulose etc. can delay medicine dissolution velocity in vivo, by both suitable collocation and generation synergism, just can effectively control medicine rate of release in vivo.
3. if there is not slow release method, medicine can be concentrated rapid release in vivo, discharges if there is the medicine of side effect once to concentrate, and will produce very strong toxic and side effects to human body.And through after the slow release method, drug slow discharges, and the medication amount that at every turn discharges is lower, just can not produce toxic and side effects.General medicine all has only certain action time (being the half-life), and just must once more take medicine after finishing action time, and the slow release method continual release medicine of energy just, does not need to take once more just to reach same effect, so can reduce dose.The medicine of same dosage, after concentrated the release, because the cause that absorbs, unnecessary amount will be discharged; And slow release method, same dosage can reach the purpose of whole absorptions by slowly discharging, thereby strengthens the effect of medicine.
4. the present invention is according to the difference of active component, after carrying out different combinations, can play cooperative effect, rather than simple stack, through relevant experimental study, the present invention can bring into play the speed of obvious control drug release, in 24 hours, can discharge medicine lentamente, enduringly, reduce and take frequency, only need once every day, avoids or reduce blood medicine " peak valley " phenomenon, easily accepted by the patient, and the curative effect and the safety that can improve medicine, increase patient compliance and reduce medicine and cause the ability of toxic and side effects more powerful because of blood concentration fluctuation.
The claimed description that has scope to be not limited only to the foregoing description of the present invention.
Claims (7)
1. oral sustained release administration granule, it is characterized in that forming by active ingredient, carrier, it is 15%～80% that active ingredient accounts for percentage by weight, it is 20～85% that carrier accounts for percentage by weight, wherein carrier is by disintegrating agent or binding agent or combination, and active ingredient is any or multiple combination in resveratrol, Quercetin, anthocyanidin, oligomeric proanthocyanidin, glucosan, flavonoid, tea polyphenols, the vitamin.
2. oral sustained release administration granule according to claim 1 is characterized in that it is 0% to 80% that disintegrating agent accounts for vehicle weight percentage ratio, and binder constitutes vehicle weight percentage ratio is 20% to 100%.
3. oral sustained release administration granule according to claim 1 and 2, it is characterized in that disintegrating agent is any in microcrystalline Cellulose, Powderd cellulose, dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, the cross-linking sodium carboxymethyl cellulose, binding agent is any or multiple composition in ethyl cellulose and aqueous dispersion thereof, polyacrylic resin, the polyvinylpyrrolidone.
4. according to claim 1 or 2 or 3 described oral sustained release administration granules, it is characterized in that the percentage by weight that unit dose contains active ingredient is 73.75%; Microcrystalline Cellulose is 20% in the carrier, and ethyl cellulose is 5%, polyvinylpyrrolidone 1.5%, and three's sum is 26.5%.
5. according to claim 1,2 and 3 described oral sustained release administration granules, it is characterized in that unit dose contains active ingredient 52.5%; In the carrier ethyl cellulose be 36.7%, polyacrylic resin 10.1%, sum of the two is 46.8%.
6. according to claim 1,2 and 3 described oral sustained release administration granules, it is characterized in that it is 40% that unit dose contains active ingredient; Microcrystalline Cellulose is 15% in the carrier, and ethyl cellulose is 35%, and the aqueous dispersion of ethyl cellulose is 10%.
7. according to claim 1,2 and 3 described oral sustained release administration granules, it is characterized in that unit dose contains active ingredient 16.2%; Microcrystalline Cellulose is 61.8% in the carrier, and the aqueous dispersion of ethyl cellulose is 22.0%, and sum of the two is 83.8%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910181933A CN101623269A (en) | 2009-08-04 | 2009-08-04 | Oral sustained release granules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910181933A CN101623269A (en) | 2009-08-04 | 2009-08-04 | Oral sustained release granules |
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| CN101623269A true CN101623269A (en) | 2010-01-13 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953506A (en) * | 2010-05-28 | 2011-01-26 | 西南大学 | Beta-glucan-tea polyphenol compound and application thereof |
| CN102525939A (en) * | 2010-12-15 | 2012-07-04 | 重庆华邦制药股份有限公司 | Para-aminosalicylic acid sustained-release pellet with high drug-loading rate and enteric-coated preparation thereof |
| CN102824325A (en) * | 2012-09-24 | 2012-12-19 | 盐城师范学院 | Quercetin sustained release tablet and preparing method thereof |
| CN103221036A (en) * | 2010-10-01 | 2013-07-24 | 阿普塔利斯制药有限公司 | Enteric coated, low-strength pancrelipase formulations |
| CN105748410A (en) * | 2014-12-15 | 2016-07-13 | 北京阜康仁生物制药科技有限公司 | Preparation technique for improving dissolution rate and stability of insoluble drug |
| CN108968051A (en) * | 2018-08-06 | 2018-12-11 | 大连医诺生物股份有限公司 | Resveratrol sustained release preparation and preparation method thereof |
-
2009
- 2009-08-04 CN CN200910181933A patent/CN101623269A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953506A (en) * | 2010-05-28 | 2011-01-26 | 西南大学 | Beta-glucan-tea polyphenol compound and application thereof |
| CN101953506B (en) * | 2010-05-28 | 2012-12-05 | 西南大学 | Beta-glucan-tea polyphenol compound and application thereof |
| CN103221036A (en) * | 2010-10-01 | 2013-07-24 | 阿普塔利斯制药有限公司 | Enteric coated, low-strength pancrelipase formulations |
| CN108187033A (en) * | 2010-10-01 | 2018-06-22 | 阿普塔利斯制药有限公司 | The low-intensity Cotazym of enteric coating |
| CN102525939A (en) * | 2010-12-15 | 2012-07-04 | 重庆华邦制药股份有限公司 | Para-aminosalicylic acid sustained-release pellet with high drug-loading rate and enteric-coated preparation thereof |
| CN102525939B (en) * | 2010-12-15 | 2015-08-26 | 重庆华邦制药有限公司 | High drug load para-aminosalicylic acid slow-release micro-pill and enteric coated preparation thereof |
| CN102824325A (en) * | 2012-09-24 | 2012-12-19 | 盐城师范学院 | Quercetin sustained release tablet and preparing method thereof |
| CN105748410A (en) * | 2014-12-15 | 2016-07-13 | 北京阜康仁生物制药科技有限公司 | Preparation technique for improving dissolution rate and stability of insoluble drug |
| CN105748410B (en) * | 2014-12-15 | 2020-06-05 | 北京阜康仁生物制药科技有限公司 | Preparation technology for improving dissolution rate and stability of insoluble drug |
| CN108968051A (en) * | 2018-08-06 | 2018-12-11 | 大连医诺生物股份有限公司 | Resveratrol sustained release preparation and preparation method thereof |
| CN108968051B (en) * | 2018-08-06 | 2022-07-12 | 大连医诺生物股份有限公司 | Resveratrol sustained-release preparation and preparation method thereof |
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Open date: 20100113 |