CN1660076A - Preparation of slowly releasing silybum mariamum - Google Patents
Preparation of slowly releasing silybum mariamum Download PDFInfo
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- CN1660076A CN1660076A CN 200410066063 CN200410066063A CN1660076A CN 1660076 A CN1660076 A CN 1660076A CN 200410066063 CN200410066063 CN 200410066063 CN 200410066063 A CN200410066063 A CN 200410066063A CN 1660076 A CN1660076 A CN 1660076A
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Abstract
A slowlly-releasing silymarinum is prepared through preparing the dispersed solid silymarinum from PEG, PVP and Puliunike and preparing its inclusion compound by use of beta-CD or HB-beta-CD. Another process is also disclosed.
Description
Technical field: the present invention relates to slow releasing preparation of Herba Silybi mariani and preparation method thereof.
Background technology: Herba Silybi mariani system from plant Compositae Herba Silybi mariani (Silybum marianum) fruit extraction separation and a kind of flavone compound.Silymarin is in late 1960s, the West Germany pharmacy men that with HWagner are representative find, comprise silibinin (silybin), silidianin (silydianin), Silychristin (silychristin) and silybonol (silybonol), be generically and collectively referred to as silymarin (silymarin).Silybin meglumine is the addition product of silibinin and meglumine, belongs to the soluble derivative of silibinin.
Chinese patent application 1543943 (application number 200310105194.3) discloses " oral silymarin slow releasing preparation and preparation method thereof ", and its technology is to be that carrier is prepared into the technology that solid dispersion is made slow releasing preparation again with silymarin with a kind of PVPK15.
Summary of the invention: the present invention is the slow releasing preparation of development Herba Silybi mariani, it mainly is the problem that solves insoluble drug silymarin slow release, it at first is the dissolubility that improves insoluble drug, the dissolubility of silymarin in water is 0.0401mg/ml, silymarin belongs to insoluble drug, if adopt common galenic pharmacy means such as micronization, add surfactant, all can not significantly improve its dissolubility, bioavailability is lower in vivo to cause it, can only adopt on the galenic pharmacy some new techniques as the preparation solid dispersion, cyclodextrin clathrate, as adopt PEG, PVP, general sulfur Buddhist nun restrains silymarin solid dispersion fully, adopt β-CD, HP-β-CD prepares clathrate, can significantly improve its dissolubility, thereby improve its bioavailability; Perhaps adopt soluble derivative silibinin-meglumine salt, the silymarin-phthalic monoester sodium salt of silymarin, silibinin-cyclodextrin, silibinin-phosphatidylcholine double salt is then by adding the release of control medicines such as slow controlled-release material such as hydroxypropyl emthylcellulose (HPMC), Rikemal B 200 (Comprital 888 ATO), ethyl cellulose, acrylic resin, Ka Bopu, octadecanol, stearic acid, sodium carboxymethyl cellulose, sodium alginate.
The present invention has prepared the solid dispersion of silymarin-PEG4000, silymarin-PEG6000, silymarin and PEG6000, Tween-80 mixed carrier, and its dissolution have significance ground than Herba Silybi mariani and improves.Again by adding the release of some slow-release material control medicines.
The present invention has prepared silymarin-PVP
K15, silymarin-PVP
K25, silymarin-PVP
K30, silymarin-PVP
K60, silymarin-PVP
K90Solid dispersion, its dissolution have significance ground than Herba Silybi mariani and improves.Wherein, silymarin-PVP
K25, silymarin-PVP
K30, silymarin-PVP
K60, silymarin-PVP
K90The stability of solid dispersion obviously is better than silymarin-PVP
K15Studies have shown that silymarin-PVP
K15Easilier separate out crystallization, make the solid dispersion poor stability.And silymarin-PVP
K60, silymarin-PVP
K90Solid dispersion promptly has certain slow releasing function, silymarin-PVP
K60, silymarin-PVP
K90Solid dispersion adds common filler such as low viscous HPMC can reach slow release effect.Silymarin-PVP
K25, silymarin-PVP
K30Add high-molecular weight HPMC or low-molecular-weight HPMC all can reach slow release effect, just proportioning is slightly different.Feature of the present invention is to adopt PVP
K25, PVP
K30, PVP
K60, PVP
K90The solid dispersion of preparation silymarin can possess better stability, can both improve the dissolubility of medicine again, under some proportioning, also has certain slow releasing function.
The present invention has prepared silymarin-HP-beta-CD inclusion, and its dissolution have significance ground than Herba Silybi mariani and improves, and adds surfactant again and improves its dissolution jointly.The release that adds some framework material control medicines again.
The silymarin solid dispersion that the present invention is making, on the basis of clathrate or adopt silibinin-meglumine, add conventional slow-release material such as hydroxypropyl emthylcellulose, ethyl cellulose, Rikemal B 200, Ka Bopu, sodium alginate, octadecanol, sodium carboxymethyl cellulose, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava, polyvinyl alcohol, acrylic resin etc., can add filler commonly used, lubricant, fluidizer, surfactant, binding agent, disintegrating agent, bleach activator, foaming agent etc., as the surfactant Tweens, sodium lauryl sulphate etc., the fluidizer stearic acid, magnesium stearate, Pulvis Talci, micropowder silica gel etc., foaming agent carbonate, bicarbonate, carbonate and citric acid share, bicarbonate and tartaric acid share etc., can be pressed into matrix tablet commonly used, perhaps by a part of rapid release, the double-deck matrix tablet that part slow release is formed, perhaps adopt bleach activator such as octadecanol, hexadecanol, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava etc., adopt foaming agent carbonate, bicarbonate, carbonate and citric acid share, bicarbonate and tartaric acid such as share at the Entogastric lingering sheet of making, perhaps adopt the silymarin solid dispersion, clathrate, silibinin-meglumine and adjuvant commonly used are made common label, the ball core, by packaging technique as using ethyl cellulose, acrylic resin, coating materials such as cellulose acetate reach slow releasing function.
The slow releasing preparation of Herba Silybi mariani, it is characterized in that: containing PEG, PEG-surfactant, PVP in the said preparation is the silymarin solid dispersion of carrier,, containing H-β-CD is the silymarin clathrate of carrier, wherein the ratio of silymarin and carrier is 1: 1～15.
The slow releasing preparation of Herba Silybi mariani is characterized in that: the principal agent composition of said preparation is the soluble derivative silybin meglumine of silibinin.
The slow releasing preparation of Herba Silybi mariani is characterized in that also containing hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or wherein combination arbitrarily.
The slow releasing preparation of Herba Silybi mariani is characterized in that silymarin or silybin meglumine: hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or the ratio that wherein makes up arbitrarily are 1: 0.1～10.
The slow releasing preparation of Herba Silybi mariani is characterized in that: the adding hydrophilic gel matrix material is hydroxypropyl emthylcellulose, Ka Bopu, sodium carboxymethyl cellulose, sodium alginate or wherein combination arbitrarily; Wax lipid framework material is octadecanol, Rikemal B 200, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava or wherein combination arbitrarily; Insoluble framework material is ethyl cellulose, acrylic resin, polrvinyl chloride, polyvinyl alcohol or wherein combination arbitrarily.
The slow releasing preparation of Herba Silybi mariani is characterized in that: can add methylcellulose, polyvinylpyrrolidone, lactose, microcrystalline Cellulose, starch, Icing Sugar, sodium lauryl sulphate, tween, sodium bicarbonate or wherein combination arbitrarily.
The slow releasing preparation of Herba Silybi mariani, it is characterized in that silymarin or silybin meglumine: hydroxypropyl emthylcellulose, ethyl cellulose, Rikemal B 200, Ka Bopu, sodium alginate, octadecanol, hexadecanol, sodium carboxymethyl cellulose, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava, polyvinyl alcohol, acrylic resin or the ratio that wherein makes up arbitrarily are 1: 0.1～10.
The slow releasing preparation of Herba Silybi mariani, it is characterized in that silymarin, silybin meglumine: hydroxypropyl emthylcellulose: Ka Bopu, octadecanol, hexadecanol, sodium carboxymethyl cellulose, Rikemal B 200, stearic acid, glyceryl monostearate, Cera Flava, polyvinylpyrrolidone, ethyl cellulose, polyvinyl alcohol, acrylic resin, sodium alginate or the ratio that wherein makes up arbitrarily are 1: 0.1～10: 0.1～10.
The slow releasing preparation of Herba Silybi mariani is characterized in that, said preparation can be oral sustained release, controlled release capsule, and wherein implant is piller, film controlled release small pieces or the film controlled release piller of matrix type; Said preparation can be oral sustained release, controlled release tablet, and wherein these tablets are matrix tablet, double-deck matrix tablet, Entogastric lingering sheet, film controlled release tablet, osmotic pump tablet.
The preparation method of the slow releasing preparation of Herba Silybi mariani, it is characterized in that, with silymarin or silybin meglumine: after hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or wherein make up arbitrarily mixes with 1: 0.1～10, direct compression or employing dry granulation tabletting or employing wet granule compression tablet or employing solid dispersion method pelletizing press sheet, perhaps make micropill, adopt ethyl cellulose, acrylic resin, cellulose acetate to carry out coating.
Description of drawings:
Fig. 1 is embodiment 1 a silymarin tablet stripping curve
Fig. 2 is embodiment 2 silymarin slow releasing tablet release profiles
Fig. 3 is embodiment 3 silymarin slow releasing tablet release profiles
Fig. 4 is embodiment 4 silymarin slow releasing tablet release profiles
Fig. 5 is embodiment 5 silymarin slow releasing tablet release profiles
Fig. 6 is embodiment 6 silymarin slow releasing tablet release profiles
Fig. 7 is embodiment 7 silymarin slow releasing tablet release profiles
Fig. 8 is embodiment 8 silymarin slow releasing tablet release profiles
Fig. 9 is embodiment 9 silymarin slow releasing tablet release profiles
Figure 10 is embodiment 10 silymarin floating in stomach sheet release profiles
Figure 11 is embodiment 11 silymarin slow releasing tablet release profiles
Figure 12 is embodiment 12 silymarin slow releasing tablet release profiles
Figure 13 is embodiment 13 silymarin floating in stomach sheet release profiles
Figure 14 is embodiment 14 silymarin slow releasing tablet release profiles
Figure 15 is embodiment 16 silymarin osmotic pump tablet release profiles
Figure 16 is embodiment 18 silybin meglumine slow releasing tablet release profiles
Figure 17 is embodiment 19 silybin meglumine slow releasing tablet release profiles
Figure 18 is embodiment 20 silybin meglumine slow releasing tablet release profiles
Figure 19 is embodiment 21 silybin meglumine floating in stomach sheet release profiles
Figure 20 is embodiment 24 silybin meglumine osmotic pump tablet release profiles
The specific embodiment:
The capsular preparation of comparative example's 1 silymarin
1000
Silymarin 105g
Polyvinylpyrrolidone (K15) 525g
Microcrystalline Cellulose 100g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K15), pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Wherein, present embodiment is presented in the stable setting-out process, and it very easily separates out crystallization, and stripping is slack-off.
Dissolution determination:
By " 2000 editions two appendix XD first methods of Chinese pharmacopoeia adopt the device of dissolution method (appendix XC first method), water intaking flies the silibin slow releasing tablet, with the distilled water is solvent, rotating speed is that per minute 100 changes, respectively at 10,20, got solution 5ml in 30 minutes, add the distilled water of uniform temp, equal volume simultaneously, institute's sample thief filters immediately, gets subsequent filtrate and measures.It is an amount of to get reference substance, calculates dissolution by external standard method.
The preparation of embodiment 2 silymarin slow releasing tablet
1000 amounts
Silymarin 105g
Polyvinylpyrrolidone (K60) 525g
Ethyl cellulose (45cps) 60g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K60), pulverized 100 mesh sieves, add ethyl cellulose, microcrystalline Cellulose mix homogeneously, tabletting.Silymarin: ethyl cellulose=1: 0.57, effectively slow release.
The drug release determination of slow releasing tablet:
By " 2000 editions two appendix XD first methods of Chinese pharmacopoeia adopt the device of dissolution method (appendix XC first method), and water intaking flies the silibin slow releasing tablet, is solvent with the distilled water, rotating speed is that per minute 100 changes, respectively at 1,2,4,6, get solution 5ml in 8,12 hours, add the distilled water of uniform temp, equal volume simultaneously, institute's sample thief filters immediately, gets subsequent filtrate and measures.It is an amount of to get reference substance, calculates release by external standard method.
The preparation of embodiment 3 silymarin slow releasing tablet
1000 amounts
Silymarin 105g
Polyvinylpyrrolidone (K30) 420g
Ethyl cellulose (45cps) 100g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), pulverized 100 mesh sieves, add ethyl cellulose, microcrystalline Cellulose mix homogeneously, tabletting.Silymarin: ethyl cellulose=1: 0.95, effectively slow release.
The preparation of embodiment 4 silymarin slow releasing tablet
1000 amounts
Silymarin 105g
Polyvinylpyrrolidone (K30) 525g
Hydroxypropyl emthylcellulose (K4M) 100g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), pulverized 100 mesh sieves, add hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, tabletting.Silymarin: hydroxypropyl emthylcellulose (K4M)=1: 0.95, effectively slow release.
The preparation of embodiment 5 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
Polyvinylpyrrolidone (K90) 262.5g
Hydroxypropyl emthylcellulose (15cps) 60g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K90), pulverized 100 mesh sieves, add hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, tabletting.Silymarin: hydroxypropyl emthylcellulose (15cps)=1: 1.14, effectively slow release.Show that silymarin adopts PVP
K90The preparation solid dispersion, solid dispersion itself promptly has certain slow release effect, adds low viscous HPMC and can reach slow releasing function.
The preparation of embodiment 6 silymarin slow releasing tablet
1000 amounts
Silymarin 105g
Polyvinylpyrrolidone (K30) 525g
Hydroxypropyl emthylcellulose (15cps) 150g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), hydroxypropyl emthylcellulose, pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Silymarin: hydroxypropyl emthylcellulose (15cps)=1: 1.43, effectively slow release.Show that silymarin adopts PVP
K30The preparation solid dispersion, in add low viscous HPMC and also can reach slow releasing function.
The preparation of embodiment 7 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
Polyvinylpyrrolidone (K30) 525g
Glycerol wych-elm acid esters 50g
Lactose 50g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), pulverized 100 mesh sieves, add glycerol wych-elm acid esters, lactose mix homogeneously, tabletting.Silymarin: glycerol wych-elm acid esters=1: 0.95, effectively slow release.
The preparation of embodiment 8 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
Polyvinylpyrrolidone (K25) 210g
Carbopol (941) 30g
Microcrystalline Cellulose 50g
Sodium lauryl sulphate 20g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K25), it is standby to pulverize 100 mesh sieves.The solid dispersion of getting 2/3 amount adds carbopol, microcrystalline Cellulose, sodium lauryl sulphate mix homogeneously, tabletting.The solid dispersion tabletting that adds remaining 1/3 amount.Silymarin: carbopol=1: 0.57, effectively slow release.Because it is slower to add the carbopol release, therefore, adopt the compacting double-layer tablet, satisfy the effect of its rapid release, slow release.
The preparation of embodiment 9 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
Polyvinylpyrrolidone (K30) 210g
Sodium alginate 25g
Microcrystalline Cellulose 50g
Sodium lauryl sulphate 20g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), it is standby to pulverize 100 mesh sieves.The solid dispersion of getting 2/3 amount adds sodium alginate, microcrystalline Cellulose, sodium lauryl sulphate mix homogeneously, tabletting.The solid dispersion tabletting that adds remaining 1/3 amount.Silymarin: sodium alginate=1: 0.48, effectively slow release.Because it is slower to add the sodium alginate release, therefore, adopt the compacting double-layer tablet, satisfy the effect of its rapid release, slow release.
The preparation of embodiment 10 silymarin floating in stomach sheets
1000 amounts
Silymarin 52.5g
Polyvinylpyrrolidone (K60) 420g
Octadecanol 70g
Stearyl alcohol 40g
Microcrystalline Cellulose 50g
Sodium bicarbonate 2g
Sodium lauryl sulphate 20g
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K60), it is standby to pulverize 100 mesh sieves.Add octadecanol, stearyl alcohol, microcrystalline Cellulose, sodium bicarbonate, sodium lauryl sulphate mix homogeneously, tabletting.Silymarin: octadecanol: stearyl alcohol=1: 1.33: 0.76, effectively slow release.Tablet rose in simulated gastric fluid and floats in about about 5 minutes, and swam in the simulated gastric fluid always.Present embodiment has added and floats material octadecanol, stearyl alcohol and help and float the material sodium bicarbonate, by delaying the time that it enters small intestinal, reaches the purpose of slow release.
The preparation of embodiment 11 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
Macrogol 4000 525g
Ethyl cellulose (45cps) 100g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt fusion to prepare solid dispersion silymarin, Macrogol 4000, pulverized 100 mesh sieves, add ethyl cellulose, microcrystalline Cellulose mix homogeneously, tabletting.Preparation Macrogol 4000-silymarin solid dispersion, silymarin: ethyl cellulose=1: 1.90, effectively slow release.
The preparation of embodiment 12 silymarin slow releasing tablet
1000 amounts
Silymarin 105g
Polyethylene glycol 6000 525g
Hydroxypropyl emthylcellulose 100g
Pregelatinized Starch 50g
Preparation technology:
Adopt fusion to prepare solid dispersion silymarin, polyethylene glycol 6000, tween 80, pulverized 100 mesh sieves, add hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, tabletting.Preparation polyethylene glycol 6000, tween 80-silymarin solid dispersion, silymarin: hydroxypropyl emthylcellulose=1: 0.95, effectively slow release.
The preparation of embodiment 13 silymarin floating in stomach sheets
1000 amounts
Silymarin 105g
Polyethylene glycol 6000 525g
Hexadecanol 55g
Glycerol wych-elm acid esters 80g
Pregelatinized Starch 50g
Sodium carbonate 10g
Preparation technology:
Adopt fusion to prepare solid dispersion silymarin, polyethylene glycol 6000, tween 80, pulverized 100 mesh sieves, add glycerol wych-elm acid esters, hexadecanol, pregelatinized Starch, sodium carbonate mix homogeneously, tabletting.Preparation polyethylene glycol 6000-silymarin solid dispersion, silymarin: glycerol wych-elm acid esters: octadecanol=1: 0.76: 0.52, effectively slow release.Tablet rose in simulated gastric fluid and floats in about about 5 minutes, and swam in the simulated gastric fluid always.Present embodiment has added and floats material hexadecanol, glycerol wych-elm acid esters and help and float the material sodium carbonate, by delaying the time that it enters small intestinal, reaches the purpose of slow release.
The preparation of embodiment 14 silymarin slow releasing tablet
1000 amounts
Silymarin 52.5g
H-β-CD 525g
Hydroxypropyl emthylcellulose 30g
Lactose 80g
Preparation technology:
Adopt fusion to prepare solid dispersion silymarin, polyethylene glycol 6000, tween 80, pulverized 100 mesh sieves, add hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, tabletting.Preparation H-β-CD, tween 80-silymarin clathrate, silymarin: hydroxypropyl emthylcellulose=1: 0.57, effectively slow release.H-β-CD-silymarin clathrate itself promptly has certain slow releasing function.
The preparation of embodiment 15 silymarin slow releasing tablet
1000 amounts
Label
Silymarin 52.5g
Polyvinylpyrrolidone (K30) 525g
Microcrystalline Cellulose 50g
Coating material
Ethyl cellulose 100g
Acrylic resin 20g
Polyethylene Glycol 5g
Oleum Ricini 5g
Diethyl phthalate 5g
Acetone soln is an amount of
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K30), pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Carry out coating with above-mentioned coating material, control its release by gain in weight.Can reach slow release 4～24 hours by regulating its gain in weight.
Above-mentioned tablet can adopt and be pressed into microplate, carries out coating with slow-release material, reinstalls capsule; Also can direct compression, coating, obtain common sustained release coating sheet.
The preparation of embodiment 16 silymarin osmotic pump tablets
1000 amounts
Label
Silymarin 52.5g
Polyvinylpyrrolidone (K25) 420g
Microcrystalline Cellulose 50g
Coating material
Cellulose acetate 100g
Polyethylene Glycol 10g
Acetone soln is an amount of
Preparation technology:
Adopt solvent method to prepare solid dispersion silymarin, polyvinylpyrrolidone (K25), pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Carry out coating with above-mentioned coating material, on coated tablet, reach an aperture then.Obtain osmotic pump tablet.
The preparation of embodiment 17 silymarin slow releasing tablet
1000 amounts
Label
Silymarin 52.5g
Macrogol 4000 315g
Microcrystalline Cellulose 50g
Coating material
Acrylic resin II 80g
Polyethylene Glycol 10g
Oleum Ricini 8g
Diethyl phthalate 5g
Acetone soln is an amount of
Preparation technology:
Adopt fusion method to prepare solid dispersion silymarin, Macrogol 4000, pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Carry out coating with above-mentioned coating material, control its release by gain in weight.By the difference of tablet gain in weight, can reach 4～24 hours slow release purpose.
Above-mentioned tablet can adopt and be pressed into microplate, carries out coating with slow-release material, reinstalls capsule; Also can direct compression, coating, obtain common sustained release coating sheet.
The preparation of embodiment 18 silybin meglumine slow releasing tablet
1000 amounts
Silybin meglumine 150g
Hydroxypropyl emthylcellulose 100g
Microcrystalline Cellulose 50g
Sodium lauryl sulphate 20g
Pregelatinized Starch 50g
Magnesium stearate 10g
Preparation technology:
With micronized silybin meglumine, hydroxypropyl emthylcellulose, microcrystalline Cellulose, pregelatinized Starch, sodium lauryl sulphate mix homogeneously, granulate, add magnesium stearate, mixing, tabletting.Silybin meglumine: hydroxypropyl emthylcellulose=1: 0.67, effectively slow release.
The preparation of embodiment 19 silybin meglumine slow releasing tablet
1000 amounts
Silybin meglumine 150g
Ethyl cellulose 200g
Lactose 50g
Sodium lauryl sulphate 20g
Magnesium stearate 10g
Preparation technology:
With micronized silybin meglumine, ethyl cellulose, lactose, sodium lauryl sulphate mix homogeneously, granulate, add magnesium stearate, mixing, tabletting.Silybin meglumine: ethyl cellulose=1: 1.33, effectively slow release.
The preparation of embodiment 20 silybin meglumine slow releasing tablet
1000 amounts
Silybin meglumine 150g
Rikemal B 200 140g
Microcrystalline Cellulose 50g
Preparation technology:
Adopt fusion to prepare solid dispersion micronized silybin meglumine, Rikemal B 200, tween 80, pulverized 100 mesh sieves, add the microcrystalline Cellulose mix homogeneously, tabletting.Silybin meglumine: Rikemal B 200=1: 0.93, effectively slow release.
The preparation of embodiment 21 silybin meglumine floating in stomach sheets
1000 amounts
Silybin meglumine 150g
Hydroxypropyl emthylcellulose 100g
Octadecanol 80g
Lactose 50g
Sodium bicarbonate 20g
Sodium lauryl sulphate 10g
80% ethanol
Preparation technology:
With micronized silybin meglumine, hydroxypropyl emthylcellulose, octadecanol, lactose, sodium bicarbonate mix homogeneously, add wetting agent, the system soft material is granulated, and drying is sieved, and granulate adds the sodium lauryl sulphate mix homogeneously, tabletting.Silybin meglumine: hydroxypropyl emthylcellulose: octadecanol=1: 0.67: 0.53, effectively slow release.Tablet rose in simulated gastric fluid and floats in about about 5 minutes, and swam in the simulated gastric fluid always.Present embodiment has added to float the material octadecanol and help and has floated the material sodium bicarbonate, by delaying the time that it enters small intestinal, reaches the purpose of slow release.
The preparation of embodiment 22 silybin meglumine slow releasing tablet
1000 amounts
Label
Silybin meglumine 150g
Lactose 50g
Sodium lauryl sulphate 20g
Pulvis Talci 10g
5%PVP80% ethanol
Coating material
Ethyl cellulose 80g
Polyethylene Glycol 20g
Oleum Ricini 10g
Diethyl phthalate 10g
Acetone soln is an amount of
Preparation technology:
With micronized silybin meglumine, lactose, sodium lauryl sulphate mix homogeneously, add binding agent, the system soft material is granulated, and drying is sieved, and granulate adds the Pulvis Talci mix homogeneously, tabletting.Carry out coating with above-mentioned material, control its release by gain in weight.Can reach 4～24 hours slow releasing function.
Above-mentioned tablet can adopt and be pressed into microplate, carries out coating with slow-release material, reinstalls capsule; Also can direct compression, coating, obtain common sustained release coating sheet.
The preparation of embodiment 23 silybin meglumine slow releasing capsule
1000 amounts
The ball core
Silybin meglumine 150g
Starch is an amount of
Dextrin is an amount of
80% ethanol
Coating material
Acrylic resin II 80g
Polyethylene Glycol 20g
Oleum Ricini 10g
Diethyl phthalate 10g
Acetone soln is an amount of
Preparation technology:
With micronized silybin meglumine, starch, dextrin mix homogeneously, in coating pan, make fine pellet core with 80% alcoholic solution, carry out coating with above-mentioned material, control its release by gain in weight.And then fill capsule.Can reach 4～24 hours slow releasing function.
The preparation of embodiment 24 silybin meglumine osmotic pump tablets
1000 amounts
Label
Silybin meglumine 150g
Lactose 50g
Sodium lauryl sulphate 20g
Pulvis Talci 10g
5%PVP80% ethanol
Coating material
Cellulose acetate 80g
Polyethylene Glycol 20g
Diethyl phthalate 10g
Acetone soln is an amount of
Preparation technology:
With micronized silybin meglumine, lactose, sodium lauryl sulphate mix homogeneously, add binding agent, the system soft material is granulated, and drying is sieved, and granulate adds the Pulvis Talci mix homogeneously, tabletting.Carry out coating with above-mentioned coating solution, make coating membrane thickness, on the clothing film, punch in certain limit.Make osmotic pump tablet.Can reach slow releasing function in vivo.
Claims (10)
1, the slow releasing preparation of Herba Silybi mariani, it is characterized in that: containing PEG, PEG-surfactant, PVP in the said preparation is the silymarin solid dispersion of carrier, containing H-β-CD is the silymarin clathrate of carrier, and wherein the ratio of silymarin and carrier is 1: 1～15.
2, the slow releasing preparation of Herba Silybi mariani is characterized in that: the principal agent composition of said preparation is the soluble derivative silybin meglumine of silibinin.
3, according to claim 1,2 one of described slow releasing preparation, it is characterized in that also containing hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or wherein combination arbitrarily.
4, slow releasing preparation according to claim 3 is characterized in that silymarin or silybin meglumine: hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or the ratio that wherein makes up arbitrarily are 1: 0.1～10.
5, according to claim 3,4 one of described slow releasing preparation, it is characterized in that: the adding hydrophilic gel matrix material is hydroxypropyl emthylcellulose, Ka Bopu, sodium carboxymethyl cellulose, sodium alginate or wherein combination arbitrarily; Wax lipid framework material is octadecanol, Rikemal B 200, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava or wherein combination arbitrarily; Insoluble framework material is ethyl cellulose, acrylic resin, polrvinyl chloride, polyvinyl alcohol or wherein combination arbitrarily.
6, slow releasing preparation according to claim 3 is characterized in that: can add methylcellulose, polyvinylpyrrolidone, lactose, microcrystalline Cellulose, starch, Icing Sugar, sodium lauryl sulphate, tween, sodium bicarbonate or wherein combination arbitrarily.
7, the slow releasing preparation one of described according to claim 1 to 4, it is characterized in that silymarin or silybin meglumine: hydroxypropyl emthylcellulose, ethyl cellulose, Rikemal B 200, Ka Bopu, sodium alginate, octadecanol, hexadecanol, sodium carboxymethyl cellulose, stearic acid, stearyl alcohol, Brazil wax, glyceryl monostearate, Cera Flava, polyvinyl alcohol, acrylic resin or the ratio that wherein makes up arbitrarily are 1: 0.1～10.
8, the slow releasing preparation one of described according to claim 1 to 5, it is characterized in that silymarin, silybin meglumine: hydroxypropyl emthylcellulose: Ka Bopu, octadecanol, hexadecanol, sodium carboxymethyl cellulose, Rikemal B 200, stearic acid, glyceryl monostearate, Cera Flava, polyvinylpyrrolidone, ethyl cellulose, polyvinyl alcohol, acrylic resin, sodium alginate or the ratio that wherein makes up arbitrarily are 1: 0.1～10: 0.1～10.
9, the slow releasing preparation one of described according to claim 1 to 8 is characterized in that said preparation can be oral sustained release, controlled release capsule, and wherein implant is piller, film controlled release small pieces or the film controlled release piller of matrix type; Said preparation can be oral sustained release, controlled release tablet, and wherein these tablets are matrix tablet, double-deck matrix tablet, Entogastric lingering sheet, film controlled release tablet, osmotic pump tablet.
10, according to the preparation method of one of the described slow releasing preparation of claim 1 to 8, it is characterized in that, with silymarin or silybin meglumine: after hydrophilic gel matrix material, wax lipid framework material, insoluble framework material or wherein make up arbitrarily mixes with 1: 0.1～10, direct compression or employing dry granulation tabletting or employing wet granule compression tablet or employing solid dispersion method pelletizing press sheet, perhaps make micropill, adopt ethyl cellulose, acrylic resin, cellulose acetate to carry out coating.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100660633A CN1311822C (en) | 2004-12-16 | 2004-12-16 | Preparation of slowly releasing silybum mariamum |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100660633A CN1311822C (en) | 2004-12-16 | 2004-12-16 | Preparation of slowly releasing silybum mariamum |
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| CN1660076A true CN1660076A (en) | 2005-08-31 |
| CN1311822C CN1311822C (en) | 2007-04-25 |
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| CNB2004100660633A Expired - Fee Related CN1311822C (en) | 2004-12-16 | 2004-12-16 | Preparation of slowly releasing silybum mariamum |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101164537B (en) * | 2006-10-16 | 2010-08-25 | 江苏大学 | High-efficient oral silibinin sustained-release preparation and preparation method thereof |
| CN101530399B (en) * | 2009-04-15 | 2011-01-26 | 江苏中兴药业有限公司 | Silibinin solid self-emusifying tablet |
| CN101961319A (en) * | 2010-09-16 | 2011-02-02 | 中国药科大学 | Silybin meglumine enteric agent with high bioavailability and preparation method thereof |
| CN102008447A (en) * | 2010-12-22 | 2011-04-13 | 北京凯因科技股份有限公司 | Entecavir solid dispersion and preparation thereof |
| CN102166201A (en) * | 2011-04-25 | 2011-08-31 | 江苏大学 | Oral ciclosporin A sustained-release agent and preparation method thereof |
| CN103191439A (en) * | 2012-06-25 | 2013-07-10 | 沈阳药科大学 | Silibinin-ursodesoxycholic acid solid dispersoid and preparation method thereof |
| CN106692980A (en) * | 2015-11-16 | 2017-05-24 | 南京卡文迪许生物工程技术有限公司 | Silibinin oral solid preparation and preparation method thereof |
-
2004
- 2004-12-16 CN CNB2004100660633A patent/CN1311822C/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101164537B (en) * | 2006-10-16 | 2010-08-25 | 江苏大学 | High-efficient oral silibinin sustained-release preparation and preparation method thereof |
| CN101530399B (en) * | 2009-04-15 | 2011-01-26 | 江苏中兴药业有限公司 | Silibinin solid self-emusifying tablet |
| CN101961319A (en) * | 2010-09-16 | 2011-02-02 | 中国药科大学 | Silybin meglumine enteric agent with high bioavailability and preparation method thereof |
| CN102008447A (en) * | 2010-12-22 | 2011-04-13 | 北京凯因科技股份有限公司 | Entecavir solid dispersion and preparation thereof |
| CN102008447B (en) * | 2010-12-22 | 2012-09-26 | 北京凯因科技股份有限公司 | Entecavir solid dispersion and preparation thereof |
| CN102166201A (en) * | 2011-04-25 | 2011-08-31 | 江苏大学 | Oral ciclosporin A sustained-release agent and preparation method thereof |
| CN102166201B (en) * | 2011-04-25 | 2013-05-01 | 江苏大学 | Oral ciclosporin A sustained-release agent and preparation method thereof |
| CN103191439A (en) * | 2012-06-25 | 2013-07-10 | 沈阳药科大学 | Silibinin-ursodesoxycholic acid solid dispersoid and preparation method thereof |
| CN103191439B (en) * | 2012-06-25 | 2014-10-15 | 沈阳药科大学 | Silibinin-ursodesoxycholic acid solid dispersoid and preparation method thereof |
| CN106692980A (en) * | 2015-11-16 | 2017-05-24 | 南京卡文迪许生物工程技术有限公司 | Silibinin oral solid preparation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1311822C (en) | 2007-04-25 |
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