CN105878210A - Method for preparing prednisolone enteric drug particles - Google Patents
Method for preparing prednisolone enteric drug particles Download PDFInfo
- Publication number
- CN105878210A CN105878210A CN201610308427.7A CN201610308427A CN105878210A CN 105878210 A CN105878210 A CN 105878210A CN 201610308427 A CN201610308427 A CN 201610308427A CN 105878210 A CN105878210 A CN 105878210A
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- Prior art keywords
- prednisolone
- microgranule
- polymer
- enteric agents
- solution
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing prednisolone enteric drug particles. The method is characterized by treating a solution with an (A) Eudragit S100 polymer of a drug (B) prednisolone via a supercritical aerosol solvent extraction method to obtain drug particles of prednisolone. The method is applied to colon-specific release particle drug preparations. According to the method, the prednisolone is mixed with a pharmaceutic adjuvant which is Eudragit S100 to prepare the drug particles; the colon-specific release of the prednisolone can be implemented; the side effects of the drug can be reduced; the utilization rate of the drug in the organism can be increased.
Description
Technical field
The present invention relates to a kind of method preparing enteric agents microgranule in field of medicaments.
Background technology
The microencapsulation of medicine is to utilize naturally occurring or synthetic pharmaceutical polymers for capsule material, medicine is disperseed or is encapsulated in material
Middle formation microgranule.Drug microparticles is compared with other common drug tablets, owing to the particle diameter of drug microparticles is little, it is easy to adheres to, can increase
Adding medicine and the contact area of site of action and time of contact, bioavailability is high；The interaction of compound medicine can be reduced simultaneously
And compatible change；The rate of release of medicine can not only be controlled, moreover it is possible to by the modification to drug microparticles surface, become can timing,
Location drug delivery system.The application prospect huge due to it and the change to convenient administration mode, this research field is in recent years
By the extensive concern of Chinese scholars, the application in terms of medicament slow release, controlled release and targeted drug achieves huge progress.
In various microencapsulation methods, preparing particle diameter drug microparticles that is little and that be evenly distributed is a new challenge.
Summary of the invention
It is an object of the invention to prepare that particle diameter is little and the prednisolone enteric agents microgranule of narrow particle size distribution.
The method condition preparing prednisolone enteric agents microgranule that the present invention provides, is by a certain amount of prednisolone medicine and medicinal
Polymer Eudragit S100 is dissolved in a certain amount of organic solvent, supercritical Aerosol Solvent Extraction method (ASES) make
Globulate microgranule medicine.Described organic solvent is acetone and the mixed solvent of methanol (1:1, v/v).
The consumption of described pharmaceutically acceptable polymer Eudragit S100 is 40mg, and is dissolved in the mixed solvent of 10mL, is configured to
Polymer concentration is the solution of 4mg/mL, then adds the prednisolone of certain mass, and its consumption is 4～20mg, obtains clarifying molten
Liquid.
In described supercritical Aerosol Solvent Extraction method, the pressure of carbon dioxide is 8.0MPa, and temperature is 35.0 DEG C, charging speed
Degree is 0.5mL/min, and carbon dioxide outlet flow velocity is 120L/h.
The present invention utilizes supercritical Aerosol Solvent Extraction method to prepare prednisolone drug microparticles, explores and prepares the medicine that particle diameter is little
The condition of polymer particles.It is thus possible to this understanding, particle diameter is prepared by supercritical Aerosol Solvent Extraction method less
Prednisolone enteric agents microgranule.Allow medicament to location release in colon, drug microparticles and colon portion can be increased substantially
The contact of position and action time, significantly improve its bioavailability and alleviate its side reaction in human body.The method has technique
Simply, the advantage such as easily controllable.
Accompanying drawing explanation
Fig. 1 is that supercritical Aerosol Solvent Extraction method (ASES) prepares prednisolone enteric agents microgranule flow chart.
Fig. 2 is the mass ratio of prednisolone when being 50% (w/w), prepares the electromicroscopic photograph of prednisolone enteric agents microgranule.
Detailed description of the invention
The preparation of prednisolone spherical enteric agents microgranule.
This example is to prepare prednisolone spherical enteric agents spherical particle by supercritical Aerosol Solvent Extraction method.Wherein prepare
Particle device is supercritical Aerosol Solvent Extraction method (ASES) device, as shown in Figure 1.
(1) the Eudragit S100 first weighing 40mg is dissolved in the acetone of 10ml and the mixed solvent of methanol, adds
The prednisolone of certain mass, fully dissolves.
(2) controlled the temperature in water bath by heater, be accurate to ± 0.1 DEG C.The CO provided by steel cylinder2Inject through plunger displacement pump
In whole device, then the pressure by ISCO pump control system, after being raised to the pressure set, it is accurate to ± 0.1MPa, stable
Device pressure and temperature 30min.
(3) then, close ISCO pump, it is ensured that in the case of the pressure of system is constant, start HPLC constant flow pump with 0.5mL/min
Flow velocity in autoclave, inject prednisolone and the mixed solution of Eudragit S100 polymer.
(4) after solution adds, close HPLC pump and respective valves, open ISCO infusion and enter CO2, rinse residual
Organic solvent, washing time is 50min.CO2The organic solvent that gas is taken out of is collected, and CO2The flow of gas passes through
Gas flowmeter is measured.
(5) stop ISCO pump, close respective valves, and to system release, obtain prednisolone pharmaceutical polymer microgranule.
(6) product in step (5) is scanned electronic microscope photos by scanning electron microscope (SEM), analyzes size and the shape of microgranule
Looks.Wherein gained prednisolone diameter of particle is at about 500nm, and size is homogeneous, is evenly distributed.
The present invention successfully prepares the prednisolone enteric agents microgranule that particle diameter is less, and it has narrower particle size distribution and preferable shape
The features such as looks.It is essential that prepare the prednisolone pharmaceutical polymer microgranule that particle diameter is little so that it is can release in colon site location
Put, increase substantially its adhesion with site of action and time of contact, thus improve its bioavailability.Present invention success
Prepare the spherical drug microparticles of prednisolone enteric, explore the condition obtaining pharmaceutical polymer microgranule, fixed for preparing other colons
Position release preparation microgranule provides method and reference.
Claims (6)
1. the method preparing prednisolone enteric agents microgranule, prednisolone and pharmaceutic adjuvant Eudragit
The mixed solution of S100 polymer, by the polyacrylic resin 40mg that (A) model is Eudragit S100,
(B) prednisolone takes 4～20mg, and (C) acetone and methanol 1:1 (v/v) form 10ml, use high density
CO2Gas prepares prednisolone enteric agents microgranule by supercritical Aerosol Solvent Extraction method.
The method preparing prednisolone enteric agents microgranule the most according to claim 1, is characterized in that, institute
The medicine stated and polymer solution, based on the weight of compositions, the weight ratio shared by component A is 60%～90%,
Weight ratio shared by component B is 9%～40%, and component C is organic mixed solvent, the polymer of configuration solution
Concentration is 4mg/mL.
The method preparing prednisolone enteric agents microgranule the most according to claim 1, is characterized in that,
The conditional parameter of described supercritical Aerosol Solvent Extraction method, wherein pressure is 8.0MPa, and temperature is
35.0 DEG C, its charging rate is 0.5mL/min, and carbon dioxide outlet flow velocity is 120L/h.
The method preparing prednisolone enteric agents microgranule the most according to claim 1, is characterized in that,
Described high density gas CO2Prednisolone enteric agents is prepared micro-by supercritical Aerosol Solvent Extraction method
The method of grain, comprises the steps:
(1) prednisolone medicine and the configuration of polymer mixed solution: weigh a certain amount of Eudragit S100
Polymer, joins in a certain amount of acetone and methanol mixed solvent, dissolves fully, adds medicine prednisone
Dragon, stirring is to clear solution；
(2) by ISCO pump and water bath device supercritical aerosol solvent extraction device is pressurized to 8.0MPa and
35.0 DEG C, then by HPLC pump in autoclave with the speed injection of medicine of 0.5mL/min and polymer
Mixed solution, injects solution to full dose；
(3) after prednisolone pharmaceutical polymer microgranule fully separates out, by CO2Micro-to the pharmaceutical polymer of gained
Granule product is dried.
5. the method preparing prednisolone enteric agents microgranule described in claim 4, it is characterised in that institute
The step (2) stated is:
(1) CO is first used2Gas washes out the air in device, then by water bath device, device is warmed up to 35 DEG C,
Then, then device is pressurized to 8.0MPa, while the pressure and temperature of stabilisation systems, keeps 30min；
(2) injected after solution completes in autoclave by HPLC pump, be then turned on CO2Outlet valve, washes out it
In organic solvent.
6. the method preparing prednisolone enteric agents microgranule described in claim 4, it is characterised in that institute
The step (3) stated is: after injection solution completes, continue to be passed through CO2Gas 50min, makes obtained medicine
Thing polymer particles is the driest.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308427.7A CN105878210A (en) | 2016-05-10 | 2016-05-10 | Method for preparing prednisolone enteric drug particles |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308427.7A CN105878210A (en) | 2016-05-10 | 2016-05-10 | Method for preparing prednisolone enteric drug particles |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1470240A (en) * | 2003-06-25 | 2004-01-28 | 暨南大学 | Controllable release system of glucocorticoid and its preparation and use |
| CN101015558A (en) * | 2007-03-08 | 2007-08-15 | 北京化工大学 | Preparation of superfine prednisolone powder |
| CN104208040A (en) * | 2014-08-25 | 2014-12-17 | 北京化工大学常州先进材料研究院 | Method for preparing medicinal auxiliary Eudragit S100 polymer particle |
-
2016
- 2016-05-10 CN CN201610308427.7A patent/CN105878210A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1470240A (en) * | 2003-06-25 | 2004-01-28 | 暨南大学 | Controllable release system of glucocorticoid and its preparation and use |
| CN101015558A (en) * | 2007-03-08 | 2007-08-15 | 北京化工大学 | Preparation of superfine prednisolone powder |
| CN104208040A (en) * | 2014-08-25 | 2014-12-17 | 北京化工大学常州先进材料研究院 | Method for preparing medicinal auxiliary Eudragit S100 polymer particle |
Non-Patent Citations (2)
| Title |
|---|
| 刘克等: "超临界CO2气溶胶溶剂萃取法制备尤特奇S100纳米颗粒", 《北京化工大学学报( 自然科学版)》 * |
| 窦若岸: "超临界二氧化碳技术制备聚合物微粒及载药微粒", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
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