CN103181901A - Dihydroartemisinin controlled-release preparation used for treating lupus erythematosus - Google Patents
Dihydroartemisinin controlled-release preparation used for treating lupus erythematosus Download PDFInfo
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Abstract
The invention discloses a dihydroartemisinin controlled-release preparation used for treating lupus erythematosus. The controlled-release preparation shows at least one property of the following: (1) according to an in-vitro release curve, when the preparation is placed for 0.5h according to a standard dissolution test, an accumulative release rate of dihydroartemisinin is 10-25%; and (2) according to a healthy adult single-dose oral administration dihydroartemisinin in-vivo absorption curve, an average time for 40% absorption is longer than approximately 2h, and/or an average time for 70% absorption is longer than approximately 6h. With the preparation, dihydroartemisinin in-vivo release speed can be controlled. The preparation can be taken only once every day, and long-time effective blood concentration can be maintained, such that medication is more convenient. The preparation has stable performance, and low toxic and side effect. Because the preparation only needs to be taken once a day, treatment cost is reduced.
Description
Technical field
The present invention relates to pharmaceutical field, be specifically related to be used for the treatment of the dihydroarteannuin controlled release preparation of lupus erythematosus.
Background technology
Lupus erythematosus especially systemic lupus erythematosus (sle) (SLE) is a kind of systemic disease of complexity, not only invades skin, and invades connective tissue, blood vessel, each system's organ of internal organs, is a kind of autoimmune disease of refractory.In recent years, the sickness rate of SLE has the trend of continuous rising, according to investigations, at present the prevalence of whole world SLE approximately is 17/10-48/10 ten thousand, in the U.S., more than 18 years old among the crowd, prevalence is 50.8/10 ten thousand, the population of China prevalence is 30-70/10 ten thousand, is only second to Black people (1,00/,100,000), occupies second in the whole world.
Treatment to lupus erythematosus, doctor trained in Western medicine is many with heavy dose of steroid 17-hydroxy-11-dehydrocorticosterone (abbreviation hormone) and immunosuppressant treatment, can control the state of an illness to the part patient, but long-term prescription then causes serious toxic and side effects and complication, even become the main cause that this disease causes death, though even some case used heavy dose of hormone state of an illness still uncontrollable, treatment that therefore should disease has become the difficult problem of medical circle.The traditional Chinese medical science adopts the policy of determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs, developed the medicine of some therapy system lupus erythematosus in recent years, be the patent of invention of CN102284002A as publication number, disclose a kind of Chinese medicine for the treatment of lupus erythematosus, comprised following component in weight portion: the Radix Astragali 25～35, Rhizoma Polygonati 12～18, Caulis Spatholobi 25～35, Radix Gentianae Macrophyllae 25～35, Zaocys 4～8, Radix Salviae Miltiorrhizae 25～35, Plumula Nelumbinis 8～16, Rhizoma Polygonati Odorati 6～12, Radix Ginseng 4～8, the Radix Paeoniae Alba 12～18, Radix Angelicae Sinensis 12～18, Fructus Ligustri Lucidi 25～35, Radix Rehmanniae Preparata 25～35, Rhizoma Coptidis 4～8.The curative effect of this Chinese medicine is better, but need there be inconvenience in Chinese medicine composition by practical situation change dose even the composition of doctor according to the patient usually.
At present, dihydroarteannuin generally is used to malaria prophylaxis and treatment.Publication number is the patent of invention of CN1266683, the purposes of pharmaceutical composition in treatment lupus erythematosus and photosensitive diseases that contains dihydroarteannuin disclosed first, the dihydroarteannuin that contains 1～10 weight % in this pharmaceutical composition, can make solid preparation, liquid preparation and external preparation for clinical, have efficient, safe characteristics.But because the half-life of dihydroarteannuin is short, thereby need take every day repeatedly to keep effective blood drug concentration, medication and inconvenience.Still be not used at present the relevant report of the dihydroarteannuin controlled release preparation of lupus erythematosus zhiliao.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of by controlling dihydroarteannuin rate of release in vivo to keep the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus of effective blood drug concentration for a long time.
The dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus of the present invention is made up of fast release micropill and controlled release micro pill, and described fast release micropill is to be made by micronization dihydroarteannuin and auxiliary material A, and wherein the weight ratio of dihydroarteannuin and auxiliary material A is 1: 1～4; Or made by dihydroarteannuin solid dispersion and auxiliary material B, wherein the weight ratio of dihydroarteannuin and auxiliary material B is 1: 2～3;
Described controlled release micro pill is to make the ball core by micronization dihydroarteannuin and adjuvant C to form by coating, and wherein the weight ratio of dihydroarteannuin and adjuvant C is 1: 2～6;
The weight ratio of described dihydroarteannuin in fast release micropill and controlled release micro pill is 10～20mg: 60～90mg;
The controlled release preparation of above-mentioned composition demonstrates at least a in the following character: (a) release in vitro curve, to place 0.5 hour according to standard dissolution test (2010 editions second one of Chinese Pharmacopoeia), and the cumulative release degree of dihydroarteannuin is 10～25%; (b) for absorption curve in the peroral administration dihydroarteannuin body of normal adults single dose, wherein the time of average absorption 40% greater than the time of about 2 hours and/or average absorption 70% greater than about 6 hours.
In the technique scheme:
In the described controlled release micro pill,
Contain 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of bag piller, their weight ratio is 2～4: 1～3: 1～3, wherein, the coating material that wraps 1 layer of clothing controlled release piller is enteric solubility coating material or stomach dissolution type coating material, the coating material that wraps 2 layers of clothing controlled release piller and 3 layers of clothing controlled release of bag piller is that internal layer is the enteric solubility coating material, skin is the stomach dissolution type coating material, and account for 1～2 layer in the stomach dissolution type coatings described in 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of the bag piller, the enteric solubility coatings accounts for 2～3 layers;
Or contain the bag 1 layer of clothing controlled release piller, wrap 2 layers of clothing controlled release piller, wrap 3 layers of clothing controlled release piller and 4 layers of clothing controlled release of bag piller, their weight ratio is 2～4: 1～3: 1～3: 1～3, wherein, the coating material that wraps 1 layer of clothing controlled release piller is enteric solubility coating material or stomach dissolution type coating material, wrap 2 layers of clothing controlled release piller, the coating material that wraps 3 layers of clothing controlled release piller and 4 layers of clothing controlled release of bag piller is that internal layer is the enteric solubility coating material, skin is the stomach dissolution type coating material, and at 2 layers of clothing controlled release piller of bag, wrap the stomach dissolution type coatings described in 3 layers of clothing controlled release piller and 4 layers of clothing controlled release of the bag piller and account for 1～2 layer, the enteric solubility coatings accounts for 2～3 layers;
Or contain coated pellets 2 and the coated pellets 3 of the coated pellets 1 of 1 layer of stomach dissolution type coating material of a kind of bag, 1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2 and coated pellets 3 is 1～3: 2～4: 3～5;
Or contain coated pellets 3 and the coated pellets 4 of two kinds of bag coated pellets 1 of 1 layer of stomach dissolution type coating material and coated pellets 2,1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2, coated pellets 3 and coated pellets 4 is 1～3: 1～3: 2～3: 3～5.
Described auxiliary material A is made up of 1～10% disintegrating agent, 0.1～1% antioxidant, 0.5～10% binding agent, 10%～20% wetting agent and the filler of surplus.Described disintegrating agent, antioxidant, binding agent and filler are conventional selection the of the prior art, and be concrete: disintegrating agent can be a kind of or two or more combination arbitrarily that is selected from dried starch, amylum pregelatinisatum, polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose sodium, carboxymethylstach sodium, carboxymethylstarch calcium, sodium starch glycollate, sodium alginate, low replacement-hyprolose, microcrystalline Cellulose, alginic acid and the sodium alginate; Described antioxidant can be butylated hydroxytoluene, or the compositions of butylated hydroxytoluene and citric acid; Binding agent can be polyvidone, hypromellose or hyprolose etc., and wetting agent can be purified water, ethanol or the mixed liquor of the two; Filler can be a kind of or two or more combination arbitrarily in lactose, mannitol, microcrystalline Cellulose or starch, dextrin, sucrose, sorbitol, calcium hydrogen phosphate, calcium phosphate and the calcium sulfate.
Described auxiliary material B is made up of 1～10% disintegrating agent, 0.1～1% antioxidant, 0.5～10% binding agent, 10%～20% wetting agent and the filler of surplus.Described disintegrating agent, binding agent, antioxidant, wetting agent and filler are conventional selection the of the prior art, and concrete: described disintegrating agent, antioxidant, binding agent, wetting agent and filler are identical with the selection in the auxiliary material A.
Described adjuvant C is made up of 1～5% disintegrating agent, 0.1～20% binding agent, 0.1～1% antioxidant, 10%～20% wetting agent and the filler of surplus.Described disintegrating agent, binding agent, antioxidant, wetting agent and filler are conventional selection the of the prior art, and be concrete: disintegrating agent can be a kind of or two or more combination arbitrarily that is selected from dried starch, amylum pregelatinisatum, polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose sodium, carboxymethylstach sodium, carboxymethylstarch calcium, sodium starch glycollate, sodium alginate, low replacement-hyprolose, microcrystalline Cellulose, alginic acid and the sodium alginate; Described antioxidant can be butylated hydroxytoluene, or the compositions of butylated hydroxytoluene and citric acid; Binding agent can be polyvidone, hypromellose or hyprolose etc., and wetting agent can be purified water, ethanol or the mixed liquor of the two; Filler can be a kind of or two or more combination arbitrarily that is selected from lactose, mannitol, microcrystalline Cellulose or starch, dextrin, sucrose, sorbitol, inorganic salts (calcium hydrogen phosphate, calcium phosphate, calcium sulfate etc.) and the Polyethylene Glycol.
When containing 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of bag piller in the controlled release micro pill, their weight ratio is preferably 2: 3: 3;
When containing 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and bag 3 layers of clothing controlled release piller and 4 layers of clothing controlled release of bag piller in the controlled release micro pill, their weight ratio is preferably 3: 2: 2: 2;
When the coated pellets 2 of the coated pellets 1 that contains 1 layer of stomach dissolution type coating material of a kind of bag in the controlled release micro pill, 1 layer of enteric solubility coating material of two kind of bag and coated pellets 3; The weight ratio of described coated pellets 1, coated pellets 2 and coated pellets 3 is preferably 3: 2: 3;
The coated pellets 3 and the coated pellets 4 that in controlled release micro pill, contain two kinds of bag coated pellets 1 of 1 layer of stomach dissolution type coating material and coated pellets 2,1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2, coated pellets 3 and coated pellets 4 is preferably 1: 2: 2: 3.
Because dihydroarteannuin can pack controlled release ball core earlier one deck bottom clothing and carry out above-mentioned various coatings again the unstability of light and heat.The described coating solution that packs the bottom clothing can be conventional the selection, and concrete bottom clothing material can be: zein, IV acrylic resin, hypromellose, hyprolose or polyvidone etc.; Solvent can be selected 95% (v/v) ethanol for use.The described weightening finish that packs the bottom clothing is preferably controlled 0.5～1%.
Described stomach dissolution type coating material, enteric solubility coating material can be conventional selections the of the prior art, and concrete: the stomach dissolution type coating material can be arabic gum, gastric solubility acrylic resin, methylcellulose, hyprolose, hypromellose, gelatin, castor oil hydrogenated, glycerol, ethylene glycol, Cera Flava, Brazil wax, paraffin and spermaceti or Opadry etc.; The enteric solubility coating material can be enteric solubility acrylic resin, cellulose acetate, cellulose acetate-phthalate, phthalic acid hypromellose or Lac etc.
In the technique scheme, contain 1 layer of clothing controlled release piller of bag, bag 2 layers of clothing controlled release piller and bag 3 layers of clothing controlled release piller in the described controlled release micro pill or also contain 4 layers of clothing controlled release piller of bag, weightening finish ratio between each layer can be conventional the selection, is preferably 0.5%: 1%: 1.5%: 2%; The coated pellets 2 and the coated pellets 3 that contain the coated pellets 1 of 1 layer of stomach dissolution type coating material of a kind of bag, 1 layer of enteric solubility coating material of two kind of bag in the described controlled release micro pill, or when containing the coated pellets 3 of two kinds of bag coated pellets 1 of 1 layer of stomach dissolution type coating material and coated pellets 2,1 layer of enteric solubility coating material of two kind of bag and coated pellets 4, the weightening finish ratio is 2～4% during with stomach dissolution type coating material coating, and the weightening finish ratio is 2～6% during with enteric solubility coating material coating.
Described dihydroarteannuin solid dispersion is dihydroarteannuin to be scattered in hydrophilic carrier make.Described hydrophilic carrier is preferably selected from alkylcellulose, light alkylcellulose, light alkyl-alkyl cellulose, carboxyl alkyl cellulose, the carboxyalkyl alkylcellulose, the carboxyl alkyl cellulose ester, starch, pectin, chitin derivativ, polysaccharide, polyacrylic acid and their salt, polymethylacrylic acid and their salt, methacrylate copolymer, aminoalkyl methacrylate copolymer, polyvinyl acetal, the diethylamino acetate, sugar type surfactant, polyvinyl alcohol, polyvidone, polyvinylpyrrolidone-vinyl acetate co-polymer, in polyalkylene oxide and oxirane and the epoxy propane copolymer one or more.
Compared with prior art, the invention provides a kind of dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus, said preparation can be controlled dihydroarteannuin rate of release in vivo, the patient only need take once and can reach the purpose of keeping long-time effective blood drug concentration every day, and medication is more convenient; The said preparation stable performance, toxic and side effects is little, owing to only need take once every day, the treatment cost reduces.
Description of drawings
Fig. 1 is the release in vitro curve of the dihydroarteannuin of commercially available 10～50 μ m;
Fig. 2 is the release in vitro curve of the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus that makes of the embodiment of the invention 1,2,3 and 4, wherein,
The release in vitro curve of expression embodiment 1,
The release in vitro curve of expression embodiment 2,
The release in vitro curve of expression embodiment 3,
The release in vitro curve of expression embodiment 4.
The specific embodiment
The invention will be further described with embodiment below, but the present invention is not limited to these embodiment.
Embodiment 1
Fast release micropill: the dihydroarteannuin 20g of 10～50 μ m, mannitol 10g, lactose 10g, microcrystalline Cellulose 26g, polyvinylpolypyrrolidone 6g, butylated hydroxytoluene 0.2g, citric acid 0.1g, 20g is binding agent with hyprolose 8g, 95% (v/v) ethanol, makes fast release micropill.
Controlled release ball core: the dihydroarteannuin 80g of 10～50 μ m, sucrose 100g, starch 147g, dextrin 60g, microcrystalline Cellulose 136g, polyvidone 27g, butylated hydroxytoluene 2g, citric acid 1g, 350g is wetting agent with hypromellose 14g, 70% (v/v) ethanol, makes controlled release ball core.
Bag bottom clothing piller: controlled release ball core 540g, carry out coating with zein 5.4g, 95% (v/v) ethanol 270g mixed liquor, increase weight about 1%.
Coated pellets 1: bag bottom clothing piller 135g, with ethyl cellulose 2g, hypromellose 0.4g, Polyethylene Glycol-400 0.3g, 95% (v/v) ethanol 70g mixed liquor coating, increase weight about 2%.
Coated pellets 2: bag bottom clothing piller 202.5g, with hexadecanol 4g, acetone 300g, cellulose acetate-phthalate 2.1g mixed liquor coating increases weight about 3%.
Coated pellets 3: bag bottom clothing piller 202.5g, with cellulose acetate 8g, acetone 400g, cellulose acetate-phthalate 15g mixed liquor coating increases weight about 4%.
With fast release micropill, coated pellets 1, coated pellets 2, coated pellets 3 mix homogeneously, No. 0 capsule of fill.
The dihydroarteannuin solid dispersion: polyvidone 10g is dissolved in 100g95% (v/v) ethanol, adds the 20g dihydroarteannuin, makes it dissolving, and this solution absorbs on the 30g polyvinylpolypyrrolidone, is steamed except solvent, makes particulate.
Fast release micropill: dihydroarteannuin solid dispersion 60g, cross-linked carboxymethyl cellulose sodium 5g, lactose 5g, microcrystalline Cellulose 10g, butylated hydroxytoluene 0.2g, citric acid 0.1g are wetting agent with polyvidone 2.1g, distilled water 30g, make fast release micropill.
Controlled release ball core: micronization dihydroarteannuin 80g, starch 117g, Polyethylene Glycol-6000 150g, hyprolose 80g, microcrystalline Cellulose 110g, butylated hydroxytoluene 2g, citric acid 1g, be wetting agent with hypromellose 20g, 70% alcoholic solution 500g, make controlled release ball core.
Bag bottom clothing piller: controlled release ball core 540g, with IV acrylic resin 5.4g, 95% (v/v) ethanol 300g mixed liquor bag bottom clothing, increase weight about 1%.
Wrap 1 layer of clothing controlled release piller: bag bottom clothing piller 120g, with IV acrylic resin 0.8g, polyvidone 0.2g, Polyethylene Glycol-400 0.2g, propylene glycol 3g, 95% (v/v) ethanol 80g mixed liquor coating, increase weight about 1%.
Wrap 2 layers of clothing controlled release piller: bag bottom clothing piller 180g, with 95% ethanol 300g, cellulose acetate 4g mixed liquor coating increases weight about 2%.With IV acrylic resin 4.4g, propylene glycol 1g, 95% (v/v) ethanol 240g mixed liquor coating, increase weight about 3% again.
Wrap 3 layers of clothing controlled release piller: bag bottom clothing piller 240g, with phthalic acid hypromellose 2.4g, acetone 300g coating increases weight about 1%.With cellulose acetate 4.8g, 95% (v/v) ethanol 500g mixed liquor coating, increase weight about 2% again.Again with IV acrylic resin 4.4g, propylene glycol 1g, 95% (v/v) ethanol 240g mixed liquor coating, increase weight about 3% at last.
With fast release micropill, 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of bag piller mix homogeneously, No. 0 capsule of fill.
Embodiment 3
Fast release micropill: the dihydroarteannuin 20g of 10～50 μ m, microcrystalline Cellulose 35g, polyvinylpolypyrrolidone 4g, butylated hydroxytoluene 0.3g, citric acid 0.2g are binding agent with polyvidone 3g, 95% ethanol 30g, make fast release micropill.
Controlled release ball core: the dihydroarteannuin 60g of 10～50 μ m, sucrose 120g, microcrystalline Cellulose 300g, polyvidone 27g, butylated hydroxytoluene 3g are wetting agent with hyprolose 30, distilled water 300g, make controlled release ball core.
Coated pellets 1: controlled release ball core 67.5g, with hypromellose 1g, polyvidone 1, Polyethylene Glycol-400 0.5g, glycerol 0.5g, 70% (v/v) ethanol 150g mixed liquor coating, increase weight about 2%.
Coated pellets 2: controlled release ball core 135g, with IV acrylic resin 4g, polyvidone 1g, Polyethylene Glycol-400 0.2g, glycerol 0.2g, 95% (v/v) ethanol 300g mixed liquor coating, increase weight about 2%.
Coated pellets 3: controlled release ball core 135g, with cellulose acetate-phthalate 10g, acetone 440g, methylcellulose 5g mixed liquor coating increases weight about 4%.
Coated pellets 4: controlled release ball core 202.5g, with ethyl cellulose 10g, 95% (v/v) ethanol 350g, methylcellulose 5g mixed liquor coating increases weight about 6%.
With fast release micropill, coated pellets 1, coated pellets 2, coated pellets 3, coated pellets 4 mix homogeneously, No. 0 capsule of fill.
Fast release micropill: the dihydroarteannuin 20g of 10～50 μ m, sucrose 20g, microcrystalline Cellulose 26g, polyvinylpolypyrrolidone 6g, butylated hydroxytoluene 0.2g, citric acid 0.1g, 20g is binding agent with hyprolose 8g, 95% (v/v) ethanol, makes fast release micropill.
Controlled release ball core: the dihydroarteannuin 80g of 10～50 μ m, sucrose 100g, starch 147g, dextrin 60g, microcrystalline Cellulose 136g, polyvidone 27g, butylated hydroxytoluene 2g, citric acid 1g, 350g is wetting agent with hypromellose 14g, 70% (v/v) ethanol, makes controlled release ball core.
Bag bottom clothing piller: controlled release ball core 540g, with zein 5.4g, 95% (v/v) ethanol 300g mixed liquor bag bottom clothing, increase weight about 1%.
Wrap 1 layer of clothing controlled release piller: bag bottom clothing piller 67.5g, with hypromellose 0.4g, polyvidone 0.1g, Polyethylene Glycol-400 0.1g, propylene glycol 1.5g, 95% (v/v) ethanol 60g mixed liquor coating, increase weight about 1%.
Wrap 3 layers of clothing controlled release piller: bag bottom clothing piller 135g, with cellulose acetate 4g, 95% (v/v) ethanol 300g mixed liquor coating, increase weight about 3%.With 95% (v/v) ethanol 250g, IV acrylic resin 2.7g mixed liquor coating, increase weight about 2% again.Increase weight about 1% with hypromellose 2g, polyvidone 0.1g, Polyethylene Glycol-400 0.1g, propylene glycol 0.5g, 95% (v/v) ethanol 250g mixed liquor coating at last.
With fast release micropill, 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag, 3 layers of clothing controlled release piller of bag and 4 layers of clothing controlled release of bag piller mix homogeneously, No. 0 capsule of fill.
Claims (8)
1. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus, formed by fast release micropill and controlled release micro pill, it is characterized in that: described fast release micropill is to be made by micronization dihydroarteannuin and auxiliary material A, and wherein the weight ratio of dihydroarteannuin and auxiliary material A is 1: 1～4; Or made by dihydroarteannuin solid dispersion and auxiliary material B, wherein the weight ratio of dihydroarteannuin and auxiliary material B is 1: 2～3;
Described controlled release micro pill is to make the ball core by micronization dihydroarteannuin and adjuvant C to form by coating, and wherein the weight ratio of dihydroarteannuin and adjuvant C is 1: 2～6;
The weight ratio of described dihydroarteannuin in fast release micropill and controlled release micro pill is 10～20mg: 60～90mg;
The controlled release preparation of above-mentioned composition demonstrates at least a in the following character: (a) release in vitro curve, to place 0.5 hour according to the standard dissolution test, and the cumulative release degree of dihydroarteannuin is 10～25%; (b) for absorption curve in the peroral administration dihydroarteannuin body of normal adults single dose, wherein the time of average absorption 40% greater than the time of about 2 hours and/or average absorption 70% greater than about 6 hours.
2. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 1 is characterized in that: in the described controlled release micro pill,
Contain 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of bag piller, their weight ratio is 2～4: 1～3: 1～3, wherein, the coating material that wraps 1 layer of clothing controlled release piller is enteric solubility coating material or stomach dissolution type coating material, the coating material that wraps 2 layers of clothing controlled release piller and 3 layers of clothing controlled release of bag piller is that internal layer is the enteric solubility coating material, and skin is the stomach dissolution type coating material;
Or contain 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag, 3 layers of clothing controlled release piller of bag and 4 layers of clothing controlled release of bag piller, their weight ratio is 2～4: 1～3: 1～3: 1～3, wherein, the coating material that wraps 1 layer of clothing controlled release piller is enteric solubility coating material or stomach dissolution type coating material, the coating material that wraps 2 layers of clothing controlled release piller, 3 layers of clothing controlled release piller of bag and 4 layers of clothing controlled release of bag piller is that internal layer is the enteric solubility coating material, and skin is the stomach dissolution type coating material;
Or contain coated pellets 2 and the coated pellets 3 of the coated pellets 1 of 1 layer of stomach dissolution type coating material of a kind of bag, 1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2 and coated pellets 3 is 1～3: 2～4: 3～5;
Or contain coated pellets 3 and the coated pellets 4 of two kinds of bag coated pellets 1 of 1 layer of stomach dissolution type coating material and coated pellets 2,1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2, coated pellets 3 and coated pellets 4 is 1～3: 1～3: 2～3: 3～5.
3. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 1 is characterized in that: described auxiliary material A is made up of 1～10% disintegrating agent, 0.1～1% antioxidant, 0.5～10% binding agent, 10～20% wetting agent and the filler of surplus.
4. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 1 is characterized in that: described auxiliary material B is made up of 1～10% disintegrating agent, 0.1～1% antioxidant, 0.5～10% binding agent, 10～20% wetting agent and the filler of surplus.
5. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 1 is characterized in that: described adjuvant C is made up of 1～5% disintegrating agent, 0.1～20% binding agent, 0.1～1% antioxidant, 10～20% wetting agent and the filler of surplus.
6. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 2 is characterized in that:
When containing 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and 3 layers of clothing controlled release of bag piller in the controlled release micro pill, their weight ratio is 2: 3: 3;
When containing 1 layer of clothing controlled release piller of bag, 2 layers of clothing controlled release piller of bag and bag 3 layers of clothing controlled release piller and 4 layers of clothing controlled release of bag piller in the controlled release micro pill, their weight ratio is 3: 2: 2: 2;
When the coated pellets 2 of the coated pellets 1 that contains 1 layer of stomach dissolution type coating material of a kind of bag in the controlled release micro pill, 1 layer of enteric solubility coating material of two kind of bag and coated pellets 3; The weight ratio of described coated pellets 1, coated pellets 2 and coated pellets 3 is 3: 2: 3;
The coated pellets 3 and the coated pellets 4 that in controlled release micro pill, contain two kinds of bag coated pellets 1 of 1 layer of stomach dissolution type coating material and coated pellets 2,1 layer of enteric solubility coating material of two kind of bag; The weight ratio of described coated pellets 1, coated pellets 2, coated pellets 3 and coated pellets 4 is 1: 2: 2: 3.
7. the dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus according to claim 1, it is characterized in that: described dihydroarteannuin solid dispersion is dihydroarteannuin to be scattered in hydrophilic carrier make.
8. according to each described dihydroarteannuin controlled release preparation that is used for the treatment of lupus erythematosus in the claim 1～7, it is characterized in that: described controlled release ball core packed one deck bottom clothing earlier before carrying out coating.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
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| CN1266683A (en) * | 1999-03-16 | 2000-09-20 | 屠呦呦 | Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases |
| CN101836967A (en) * | 2010-05-17 | 2010-09-22 | 中国药科大学 | Dihydroartemisinine bilayer tablet and preparation method thereof |
| CN102038677A (en) * | 2009-10-15 | 2011-05-04 | 石雁羽 | Brominated dihydroartemisinin compound double-releasing preparation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
| WO2018157874A1 (en) * | 2017-02-28 | 2018-09-07 | 东南大学 | Dihydroartemisinin diploid derivative, pharmaceutical composition thereof, and application |
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Application publication date: 20130703 |