CN106692109A - Microporous membrane-coated controlled-release diacerein pellet and preparation method thereof - Google Patents
Microporous membrane-coated controlled-release diacerein pellet and preparation method thereof Download PDFInfo
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- CN106692109A CN106692109A CN201710000243.9A CN201710000243A CN106692109A CN 106692109 A CN106692109 A CN 106692109A CN 201710000243 A CN201710000243 A CN 201710000243A CN 106692109 A CN106692109 A CN 106692109A
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- Prior art keywords
- diacerein
- controlled release
- micropill
- microporous barrier
- pellet
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
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- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a microporous membrane-coated controlled-release trelagliptin succinate pellet and a preparation method thereof. The microporous membrane-coated controlled-release trelagliptin succinate pellet sequentially comprises a drug-containing pellet core and a controlled-release coating layer from inside to outside, wherein the drug-containing pellet core is prepared from a primary material and an auxiliary material at the ratio of (5%-20%):(80%-95%). According to the microporous membrane-coated controlled-release trelagliptin succinate pellet, a bitter taste can be coated, the effective ingredients can be dissolved out, constant long-acting plasma concentration is ensured, and the defect that a drug is discharged along with excrement before not completely released is avoided.
Description
Technical field
It is micro- more particularly, to a kind of microporous barrier controlled release coat diacerein the present invention relates to animal drug formulation art
Ball and preparation method thereof.
Background technology
1st, pharmacological action and clinical effect
Diacerein is the primary inhibitor of osteoarthritis IL-1.Confirmed through cell experiment and zoopery, the pharmacology of this product is made
With mainly having（1）This product can induce Chondrogenesis, with analgesic, anti-inflammatory and antipyretic effect；（2）Do not suppress prostaglandin and into；
（3）Play the role of to delay disease process to osteoarthritis.Pharmacokinetic shows, in animal and human body, oral is double
Vinegar it is auspicious because enter body circulation before through the Viability metabolite Rhein of deacetylation.Health adult's single oral administration reaches
Peak time is about 2.4 hours, and plasma protein binding rate is more than 99%, and plasma half-life is about 4.2 hours, the apparent biological profit of this product
Expenditure is 35%-56%., mainly through RE, fraction is also through bile excretion for metabolite Rhein.
The toxicological effect experiment of this product shows that the maximal tolerance dose of mouse and rat single-dose exceedes people's dosage
190 and 410 times, the maximal tolerance dose of dog exceedes 600 times of people's dosage（Calculated by body surface area dosage）.It is subacute, slow
Property and fetotoxicity experiment, fertility test, perinatal period and postpartum toxicity test, carcinogenic and teratology testing shows diacerein
With good security.
This product indication clinically is for treating degenerative joint disease（Osteoarthritis and relevant disease）；It is domestic
Research display, this product can significantly improve the symptoms such as the pain that osteoarthritis and relevant disease cause and joint function disturbance.Take
Start effective after 2-4 weeks, performance in 4-6 weeks is obvious.If continuous treatment is discontinued for 3 months later, curative effect is at least sustainable 1 month（Afterwards
Continuous effect）.
2nd, clinical practice
Usage and dosage is, orally.240mg-480mg (1-2), 3 times a day, or follows the doctor's advice.According to patient's state of an illness, connect
It is continuous to take for 4-12 weeks, if necessary in doctor's long-term treatment（It is not shorter than 3 months）：It is daily 1-2 times, 1 every time, take after the meal.By
May cause laxativeness in take diacerein first 2 weeks, it is therefore proposed that treatment first 4 weeks daily 1, clothes after dinner
With.After patient is adapted to medicine, dosage just should increase to that 2 times a day, after the meal orally.When doctor should determine treatment according to curative effect
Between, but the course for the treatment of should not be shorter than 3 months.In clinical trial, patient once continuously took this product 2 years and without any safety problem.If controlling
Needing to share other medicines in treatment carries out long-term treatment, should carry out within every 6 months once including the comprehensive blood including liver biochemistry enzyme
Liquid and urine test.Because this product works slowly（It is effective in 2-4 weeks after treatment）And good gastrointestinal toleration, it is proposed that giving
First 2-4 weeks of medicine can be with other anodyne or non-steroid anti-inflammatory drug use in conjunction.
Diacerein is not useable for less than 15 years old children, because this age group does not carry out any clinical trial.More than 70 years old,
And with serious renal insufficiency（CCr rate 10-30ml/min）Gerontal patient, must dosage halve or follow the doctor's advice.
Take improvement intestinal transport and（Or）During the medicine of intestinal contents property, taboo takes this medicine.To improve the biology profit of diacerein
Expenditure should avoid and meanwhile take containing aluminium hydroxide and（Or）The medicine of magnesium hydroxide.Can increase using anti-after taking diacerein
Raw element and（Or）Chemotherapeutic patient suffers from the possibility of enterocolitis, because antibiotic and chemotherapy can influence enteron aisle
Flora.Unexpected or spontaneous excessive use diacerein can cause diarrhoea.Without special solution.If diarrhoea continues, doctor need to be asked
Treatment.Internal fluid and electrolyte balance need to be repeatedly detected during emergent management.
The content of the invention
The present invention is in order to solve defect present in above-mentioned prior art and deficiency, there is provided a kind of not only to wrap to live
Bitter taste, and molten draw active ingredient, it is ensured that blood concentration is constant long-acting, it is to avoid medicine before not discharging just with excrement completely
Just microporous barrier controlled release coat diacerein micropill for the defect discharged and preparation method thereof.
Technical scheme：A kind of microporous barrier controlled release coat diacerein micropill, includes pastille successively from inside to outside
Capsule core and controlled release coating layer,
Described pellet core presses 5-20% by major ingredient and auxiliary material：The ratio composition of 80-95%, the major ingredient is diacerein, institute
Stating auxiliary material includes the one kind or several in microcrystalline cellulose, starch, lactose, dextrin, sodium carboxymethyl starch, sodium carboxymethylcellulose
Kind；
The controlled release coating layer is by undissolved polymer in the gastrointestinal tract, the pore-foaming agent that can dissolve or come off, plasticizer and resists
80-85% is pressed in glutinous agent：3-5%：0.3-0.5%：The ratio composition of 10-15%.
Preferably, the polymer undissolved in the gastrointestinal tract is by polymethacrylate resin, methyl methacrylate
With one or more compositions in butyl acrylate copolymer, the Eudragit NE 30D of commercialization；
The dissolvable or tear-away pore-foaming agent is by one or more groups in PEG, PVP, HPMC, lactose, talcum powder
Into；
The plasticizer is made up of one or two in triethyl citrate, phthalic acid methyl esters；
The antitackiness agent is made up of one or two in talcum powder, magnesium stearate.
Preferably, described pellet core is by 10% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% lactose
Composition, the controlled release coating layer is by Eudragit NE 30D aqueous dispersions 20kg, PVP1kg, talcum powder 3kg, lemon triethylenetetraminehexaacetic acid
Ester 0.1kg is constituted.
Preferably, described pellet core is by 15% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 60% lactose
Composition, the controlled release coating layer is by Eudragit NE 30D aqueous dispersions 60kg, PVP3kg, talcum powder 9kg, lemon triethylenetetraminehexaacetic acid
Ester 0.3kg is constituted.
Preferably, described pellet core is by 20% diacerein, 10% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% starch
Composition, the controlled release coating layer is by Eudragit NE 30D aqueous dispersions 20kg, PVP1kg, talcum powder 3kg, lemon triethylenetetraminehexaacetic acid
Ester 0.1kg is constituted.
Preferably, described pellet core is by 5% phosphoric acid diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 70%
Starch is constituted, and the controlled release coating layer is by Eudragit NE 30D aqueous dispersions 60kg, PVP3kg, talcum powder 9kg, citric acid
Triethyl 0.3kg is constituted.
A kind of preparation method of microporous barrier controlled release coat diacerein micropill, comprises the steps：
1）Prepare pellet core：Take during 5-20% major ingredients, 70%-90% put mixer and be well mixed, plus appropriate 5% hydroxypropyl methylcellulose
Plain sodium solution as adhesive make softwood, softwood through 0.6-0.8mm screen clothes extrude, it is round as a ball, then through fluidized drying, contained
Pill core；
2）Prepare two kinds of coating liquids of coating weight gain：By undissolved polymer in the gastrointestinal tract, the cause that can dissolve or come off
Hole agent, plasticizer and antitackiness agent press 80-85%：3-5%：0.3-0.5%：The ratio of 10-15% prepares coating liquid A and coating liquid
B,
3）It is coated：Weigh 100kg pellet cores to put in fluid bed, under fluidized state, sprayed into by spray gun respectively above-mentioned
Coating liquid A or coating liquid B, coating heats up to dry to moisture after terminating and obtains final product micropill A and micropill B less than 10%；
4）By in micropill A and micropill B input V-Mixers, mix 8 minutes, obtain finished product.
The present invention makes medicine in the given time automatically by pre- constant speed by controlling the constituent of coating membrane and capsule core
Degree release, blood concentration is in the long period constant preparation maintained in Valid concentration.It has the following advantages：Effectively cover
The bitter taste of diacerein, makes the spice addition be easily reached the therapeutic dose of 400ppm and at all not influence animal feed intake；Can
With the high temperature granulating process of resistance to complete feed；After oral, immediate release section includes that stomach and small intestine are quick in alimentary canal front section
Release, slowbreak part is discharged by predetermined speed in a long time, so that it is long totally to play rapid-action, constant duration of efficacy
Purpose.All release is complete in 8-12 hours for whole active ingredients, it is to avoid medicine quilt before being absorbed without release completely
Drain.
Sum it up, not only wrapping, bitter taste must be lived, and molten draw active ingredient, it is ensured that blood concentration is constant long-acting, keeps away
The defect that medicine is just discharged before not discharging completely with excrement is exempted from.
Specific embodiment
With reference to embodiment, the present invention is further detailed explanation, but is not the limit to the scope of the present invention
System.
Embodiment one
Prepare pellet core：Take during 10% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% lactose put mixer and mix
Close uniform, plus appropriate 5% HPMC sodium solution makes softwood as adhesive, softwood is squeezed through 0.6-0.8mm screen clothes
Go out, it is round as a ball, then through fluidized drying, obtain pellet core.
Prepare the micropill of different coating weight gains：
Coating weight gain A prescriptions：Eudragit NE 30D aqueous dispersions 20kg, PVP1kg, talcum powder 3kg, triethyl citrate
0.1kg。
Coating weight gain B prescriptions：Eudragit NE 30D aqueous dispersions 60kg, PVP3kg, talcum powder 9kg.
Weigh 100kg pellet cores to put in fluid bed, under fluidized state, above-mentioned coating prescription A or B are sprayed into by spray gun
Liquid.Coating parameter：Blower fan frequency 30,25 DEG C of temperature of charge, hydrojet speed 0.5kg/min.Coating heats up drying extremely after terminating
Moisture obtains final product semi-finished product less than 10%.
It is total mixed：By in two kinds of micropill input V-Mixers of above-mentioned coating weight gain A, B, mix 8 minutes, obtain finished product.
Embodiment two
Prepare pellet core：Take during 15% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 60% lactose put mixer and mix
Close uniform, plus appropriate 5% HPMC sodium solution makes softwood as adhesive, softwood is squeezed through 0.6-0.8mm screen clothes
Go out, it is round as a ball, then through fluidized drying, obtain pellet core.
Prepare the micropill of different coating weight gains：
Coating weight gain A prescriptions：Eudragit NE 30D aqueous dispersions 20kg, HPMC1kg, talcum powder 3kg, triethyl citrate
0.1kg。
Coating weight gain B prescriptions：Eudragit NE 30D aqueous dispersions 60kg, HPMC3kg, talcum powder 9kg, citric acid three
Ethyl ester 0.3kg.
Weigh 100kg pellet cores to put in fluid bed, under fluidized state, above-mentioned coating prescription A or B are sprayed into by spray gun
Liquid.Coating parameter：Blower fan frequency 35,28 DEG C of temperature of charge, hydrojet speed 0.4kg/min.Coating heats up drying extremely after terminating
Moisture obtains final product semi-finished product less than 10%.
It is total mixed：By in two kinds of micropill input V-Mixers of above-mentioned coating weight gain A, B, mix 8 minutes, obtain finished product.
Embodiment three
Prepare pellet core：Take during 20% diacerein, 10% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% starch put mixer and mix
Close uniform, plus appropriate 5% HPMC sodium solution makes softwood as adhesive, softwood is squeezed through 0.6-0.8mm screen clothes
Go out, it is round as a ball, then through fluidized drying, obtain pellet core.
Prepare the micropill of different coating weight gains：
Coating weight gain A prescriptions：Eudragit NE 30D aqueous dispersion 20kg, HPMC 1kg, titanium dioxide 1kg, magnesium stearate
2kg, triethyl citrate 0.1kg.
Coating weight gain B prescriptions：Eudragit NE 30D aqueous dispersion 60kg, HPMC 3kg, titanium dioxide 3kg, stearic acid
Magnesium 6kg, triethyl citrate 0.3kg.
Weigh 100kg pellet cores to put in fluid bed, under fluidized state, above-mentioned coating prescription A or B are sprayed into by spray gun
Liquid.Coating parameter：Blower fan frequency 35,30 DEG C of temperature of charge, hydrojet speed 0.6kg/min.Coating heats up drying extremely after terminating
Moisture obtains final product semi-finished product less than 10%.
It is total mixed：By in two kinds of micropill input V-Mixers of above-mentioned coating weight gain A, B, mix 8 minutes, obtain finished product.
Example IV
Prepare pellet core：Take 5% phosphoric acid diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 70% starch and put mixer
In be well mixed, plus appropriate 5% HPMC sodium solution as adhesive make softwood, softwood is through 0.6-0.8mm screen clothes
Extrusion, it is round as a ball, then through fluidized drying, obtain pellet core.
Prepare the micropill of different coating weight gains：
Coating weight gain A prescriptions：Eudragit NE 30D aqueous dispersions 18kg, HPMC1kg, titanium dioxide 1kg, magnesium stearate
2kg, triethyl citrate 0.1kg.
Coating weight gain B prescriptions：Eudragit NE 30D aqueous dispersions 55kg, HPMC3kg, titanium dioxide 3kg, stearic acid
Magnesium 6kg, triethyl citrate 0.2kg.
Weigh 100kg pellet cores to put in fluid bed, under fluidized state, above-mentioned coating prescription A or B are sprayed into by spray gun
Liquid.Coating parameter：Blower fan frequency 36,30 DEG C of temperature of charge, hydrojet speed 0.6kg/min.Coating heats up drying extremely after terminating
Moisture obtains final product semi-finished product less than 10%.
It is total mixed：By in two kinds of micropill input V-Mixers of above-mentioned coating weight gain A, B, mix 8 minutes, obtain finished product.
Claims (8)
1. a kind of microporous barrier controlled release coat diacerein micropill, includes pellet core and controlled release coating layer successively from inside to outside, its
It is characterised by：
Described pellet core presses 5-20% by major ingredient and auxiliary material：The ratio composition of 80-95%, the major ingredient is diacerein, institute
Stating auxiliary material includes the one kind or several in microcrystalline cellulose, starch, lactose, dextrin, sodium carboxymethyl starch, sodium carboxymethylcellulose
Kind；
The controlled release coating layer is by undissolved polymer in the gastrointestinal tract, the pore-foaming agent that can dissolve or come off, plasticizer and resists
80-85% is pressed in glutinous agent：3-5%：0.3-0.5%：The ratio composition of 10-15%.
2. a kind of microporous barrier controlled release coat diacerein micropill according to claim 1, it is characterised in that：It is described in stomach and intestine
Undissolved polymer is by polymethacrylate resin, methyl methacrylate and butyl acrylate copolymer, commercialization in road
Eudragit NE 30D in one or more composition；
The dissolvable or tear-away pore-foaming agent is by one or more groups in PEG, PVP, HPMC, lactose, talcum powder
Into；
The plasticizer is made up of one or two in triethyl citrate, phthalic acid methyl esters；
The antitackiness agent is made up of one or two in talcum powder, magnesium stearate.
3. a kind of microporous barrier controlled release coat diacerein micropill according to claim 2, it is characterised in that：Described pastille
Capsule core is made up of 10% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% lactose, the controlled release coating layer by
Eudragit NE 30D aqueous dispersions 20kg, PVP1kg, talcum powder 3kg, triethyl citrate 0.1kg compositions.
4. a kind of microporous barrier controlled release coat diacerein micropill according to claim 2, it is characterised in that：Described pastille
Capsule core is made up of 15% diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 60% lactose, the controlled release coating layer by
Eudragit NE 30D aqueous dispersions 60kg, PVP3kg, talcum powder 9kg, triethyl citrate 0.3kg compositions.
5. a kind of microporous barrier controlled release coat diacerein micropill according to claim 2, it is characterised in that：Described pastille
Capsule core is made up of 20% diacerein, 10% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 65% starch, the controlled release coating layer by
Eudragit NE 30D aqueous dispersions 20kg, PVP1kg, talcum powder 3kg, triethyl citrate 0.1kg compositions.
6. a kind of microporous barrier controlled release coat diacerein micropill according to claim 2, it is characterised in that：Described pastille
Capsule core is made up of 5% phosphoric acid diacerein, 20% microcrystalline cellulose, 5% carboxyrnethyl starch sodium, 70% starch, the controlled release coating layer by
Eudragit NE 30D aqueous dispersions 60kg, PVP3kg, talcum powder 9kg, triethyl citrate 0.3kg compositions.
7. the preparation method of a kind of microporous barrier controlled release coat diacerein micropill according to claim 2, it is characterised in that：
It comprises the steps：
1）Prepare pellet core：Take during 5-20% major ingredients, 80%-95% put mixer and be well mixed, plus appropriate 5% hydroxypropyl methylcellulose
Plain sodium solution as adhesive make softwood, softwood through 0.6-0.8mm screen clothes extrude, it is round as a ball, then through fluidized drying, contained
Pill core；
2）Prepare two kinds of coating liquids of coating weight gain：By undissolved polymer in the gastrointestinal tract, the cause that can dissolve or come off
Hole agent, plasticizer and antitackiness agent press 80-85%：3-5%：0.3-0.5%：The ratio of 10-15% prepares coating liquid A and coating liquid
B,
3）It is coated：Weigh 100kg pellet cores to put in fluid bed, under fluidized state, sprayed into by spray gun respectively above-mentioned
Coating liquid A or coating liquid B, coating heats up to dry to moisture after terminating and obtains final product micropill A and micropill B less than 10%；
4）By in micropill A and micropill B input V-Mixers, mix 8 minutes, obtain finished product.
8. the preparation method of a kind of microporous barrier controlled release coat diacerein micropill according to claim 7, it is characterised in that：
The step 3）In coating parameter：Blower fan frequency 30,25 DEG C of temperature of charge, hydrojet speed 0.5kg/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710000243.9A CN106692109A (en) | 2017-01-02 | 2017-01-02 | Microporous membrane-coated controlled-release diacerein pellet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710000243.9A CN106692109A (en) | 2017-01-02 | 2017-01-02 | Microporous membrane-coated controlled-release diacerein pellet and preparation method thereof |
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ID=58905807
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107929264A (en) * | 2017-12-04 | 2018-04-20 | 广东药科大学 | Diacerein sustained-release micro-spheres and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1395484A (en) * | 2000-01-12 | 2003-02-05 | 梅迪多姆实验室股份有限公司 | Substances for use in treating psoriasis |
| CN105919980A (en) * | 2016-07-07 | 2016-09-07 | 杭州爱力迈动物药业有限公司 | Micro-porous membrane release-controlling coating tilmicosin pellet and preparation method thereof |
-
2017
- 2017-01-02 CN CN201710000243.9A patent/CN106692109A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1395484A (en) * | 2000-01-12 | 2003-02-05 | 梅迪多姆实验室股份有限公司 | Substances for use in treating psoriasis |
| CN105919980A (en) * | 2016-07-07 | 2016-09-07 | 杭州爱力迈动物药业有限公司 | Micro-porous membrane release-controlling coating tilmicosin pellet and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107929264A (en) * | 2017-12-04 | 2018-04-20 | 广东药科大学 | Diacerein sustained-release micro-spheres and preparation method thereof |
| CN107929264B (en) * | 2017-12-04 | 2020-04-24 | 广东药科大学 | Diacerein slow release microsphere and preparation method thereof |
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