CN106063778A - A kind of preparation method of beclometasone transparent aqueous phase Nanodispersion - Google Patents
A kind of preparation method of beclometasone transparent aqueous phase Nanodispersion Download PDFInfo
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- CN106063778A CN106063778A CN201510191238.1A CN201510191238A CN106063778A CN 106063778 A CN106063778 A CN 106063778A CN 201510191238 A CN201510191238 A CN 201510191238A CN 106063778 A CN106063778 A CN 106063778A
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Abstract
The invention discloses the preparation method of a kind of beclometasone transparent aqueous phase Nanodispersion, the method comprises the steps: 1) beclometasone and water are added simultaneously in reactor；2) dispersant is dissolved in water, the adjuvant aqueous solution being configured to, and control aqueous temperature at 0-20 DEG C；3) in reactor, N it is passed through2Gas, regulation system temperature value preset temperature, regulation reaction system pressure reaches preset pressure；4) liquid in reactor is ejected into rapidly in the aqueous solution of adjuvant, beclometasone nano-particle i.e. Precipitation, i.e. obtains transparent aqueous phase Nanodispersion.The invention also discloses the preparation method of described beclometasone aqueous phase Nanodispersion; the inventive method uses subcritical water anti-solvent technology to prepare beclometasone nano-particle; decrease the use of organic solvent; make whole technique nontoxic, pollution-free; product no solvent residue; low production cost, has extraordinary protective effect to human body and environment.
Description
Technical field
The present invention relates to medicine and health food preparation field, particularly relate to the preparation method of a kind of beclometasone transparent aqueous phase Nanodispersion.
Background technology
Beclometasone is a kind of corticosteroids medicine with antiinflammatory action, has the multiple pharmacological effect such as antiinflammatory, antiallergic and suppression immunity.In Clinical practice, beclometasone makes the active component of medicine be transported to patient lungs in aerosol, but beclometasone is slightly water-soluble compound, but this hinders this compounds in the absorption of patient lungs, thus greatly limit the beclometasone curative effect to asthmatic patient, so, the focus that the dissolubility of raising beclometasone and bioavailability are always in drug research.
Showing after deliberation, the change of dissolution rate is the key factor of the bioavailability improving poorly water soluble drugs.Showing according to Ostwald Freundrich equation, drug-eluting speed and size of pharmaceutical particles are inversely proportional to, and reduce drug particles particle diameter and its dissolution rate can be greatly improved.In recent years, along with the development of medicine nanotechnology, many poorly water soluble drugs are prepared as nano-particle or Nanodispersion by nanotechnology so that it is bioavailability is greatly improved.Patent CN 101322682A report a kind of with high pressure homogenization method to the method preparing Nano medication dispersion；Patent CN 102188372A discloses a kind of method using spray drying method to prepare medicament nano granule.These methods can make medicament nano, and then improves its dissolution rate, but itself also has the limitation of its application, such as complicated process of preparation, and particle diameter is big, skewness, containing chemical reagent, works the mischief human body and environment etc..
Summary of the invention
The technical problem to be solved is to provide the preparation method of a kind of beclometasone granule; the method uses subcritical water anti-solvent technology to prepare beclometasone nano-particle; owing to using water as anti-solvent; greatly reduce the usage amount of organic solvent; make whole technique nontoxic, pollution-free; product no solvent residue, low production cost, human body and environment are had extraordinary protective effect.
Second technical problem to be solved by this invention is to provide the preparation method of a kind of beclometasone transparent aqueous phase Nanodispersion.
For solving above-mentioned first technical problem, the technical solution used in the present invention is to provide the preparation method of a kind of beclometasone nano-particle, and the method comprises the steps:
1) appropriate beclometasone and water are added simultaneously in reactor；
2) dispersant is dissolved in water, the adjuvant aqueous solution being configured to, and control water-soluble liquid temperature 0-20 DEG C, stir speed (S.S.) is 600-800rpm；
3) in reactor, N it is passed through2Gas, regulation system temperature value preset temperature, regulation reaction system pressure reaches preset pressure；
4) being sprayed into rapidly by liquid in reactor dissolved with in adjuvant aqueous solution, liquid spouting velocity is 5-10ml/min, beclometasone nano-particle i.e. Precipitation, forms aqueous phase Nanodispersion.
Preferably, step 1) described beclometasone quality is 18-50mg, the volume of water is 40-60ml.
Preferably, step 2) described dispersant concentration in water is 0.1-5mg/ml, dispersant is selected from Polyethylene Glycol, beta-schardinger dextrin-, hydroxypropyl methyl cellulose and polyvinylpyrrolidone.
Preferably, step 2) adjuvant aqueous temperature is 0-18 DEG C, rotating speed 500-800rpm.
Preferably, step 3) preset pressure of reaction kettle for reaction system is 6-8MPa, reaction temperature is 120-160 DEG C, and stir speed (S.S.) is 150-200rpm, and reaching the dissolution equilibrium time is 10-20min.
Preferably, step 4) described) reactor ejection beclometasone aqueous solution volume is 5-10ml, the volume of adjuvant aqueous solution is 10-50ml.
Preferably, beclometasone nano-particle, it is characterised in that: the particle diameter of described beclometasone rice grain is 50-90nm；The dissolution rate of the granule in described beclometasone Nanodispersion is dissolution 92.9%-94.6% in 120min, faster than the dissolution rate of crude drug powder body 5-10 times
The invention has the beneficial effects as follows:
1. the present invention uses subcritical water anti-solvent technology to prepare beclometasone nano-particle first.Subcritical water anti-solvent technology is the granulation technique received significant attention in recent years; owing to using water as anti-solvent; greatly reduce the usage amount of organic solvent; make whole technique nontoxic, pollution-free; product no solvent residue; low production cost, has extraordinary protective effect to human body and environment.
2. the beclometasone nano-particle obtained by the present invention has particle diameter little (particle diameter is 50-90nm), narrowly distributing, feature that stability is strong.
3. the beclometasone granule transparent nano dispersion composition obtained by the present invention is fairly simple, and stabilizer is common medicinal supplementary material.
4. the dissolution rate of the beclometasone nano-particle that prepared by the present invention is obviously improved, and in 20 minutes, saponin gets final product complete dissolution, and under equal state, saponin crude drug only has the 10-20% dissolution of total amount.
Accompanying drawing explanation
Table 1 is to prepare beclometasone transparent aqueous phase Nanodispersion different experimental conditions.
Fig. 1 is for preparing beclometasone transparent aqueous phase nano-dispersed body device flow chart；
Fig. 2 is the scanning electron microscope (SEM) photograph of beclometasone crude drug granule；
Fig. 3 is the scanning electron microscope (SEM) photograph of granule in beclometasone Nanodispersion in embodiment 3；
Fig. 4 is the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion in embodiment 4；
Fig. 5 is granule Dissolution profiles figure in aqueous in the nano-dispersed in beclometasone crude drug granule and embodiment 4；
Fig. 6 is the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion in embodiment 5；
Fig. 7 is the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion in embodiment 6；
Fig. 8 is the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion in embodiment 9；
Fig. 9 is the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion in embodiment 10；
Figure 10 is granule Dissolution profiles figure in aqueous in the nano-dispersed in beclometasone crude drug granule and embodiment 10；
The beclometasone crude drug granule that Figure 11 is and X-ray crystal diffraction (XRD) spectrogram of nano-particle in embodiment 4 and 10.
Detailed description of the invention
Below in conjunction with the accompanying drawings and the present invention is illustrated by embodiment further, but present disclosure is not limited only to the following examples or other similar examples.
Embodiment 1
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg Polyethylene Glycol to be dissolved in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 18 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 120 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out, formed transparent nano dispersion, its drug concentration is 1mg/ml.Nano-particle mean diameter is 264nm.
Embodiment 2
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg Polyethylene Glycol to be dissolved in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 18 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out, forming transparent nano dispersion, its drug concentration is 1mg/ml, and nano-particle mean diameter is 142nm.
Embodiment 3
1) weigh 50mg beclometasone and 40ml deionized water, be simultaneously introduced in reactor,；
2) weighing 7.5mg Polyethylene Glycol to be dissolved in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out, form transparent nano dispersion, its drug concentration is 1mg/ml, Fig. 1 is to prepare beclometasone Nanodispersion flow chart, and Fig. 2 is the scanning electron microscope (SEM) photograph of beclometasone crude drug powder body, and granule-morphology is uneven, particle diameter is very big, from 10 μm to 40 μm；Fig. 3 is to implement the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion that 3 examples prepare, and mean diameter is 78nm.
Embodiment 4
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg Polyethylene Glycol to be dissolved in 15ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out, form transparent nano dispersion, its drug concentration is 0.33mg/ml, Fig. 4 is the scanning electron microscope (SEM) photograph implementing the beclometasone Nanodispersion granule that 4 examples prepare, granule is unifonn spherical, particle diameter narrow distribution, and mean diameter is 43nm.
Gained beclometasone Nanodispersion contrasts with water, it can be seen that Nanodispersion transparency is close with water, and stable in properties.
The bright Nanodispersion of propanoic acid times chlorine that Fig. 4 is beclometasone crude drug Dissolution profiles figure in aqueous and embodiment 4 prepares Dissolution profiles figure in aqueous, as can be seen from Figure 5, in 20min, the only dissolution 10.54% of beclometasone crude drug powder body, beclometasone Nanodispersion then dissolution 45.75%, it it is 4 times of crude drug dissolution rate, when the time arrives 120min, beclometasone Nanodispersion dissolution is 92.89%, the most almost it is completely dissolved, and crude drug only dissolution 20.89%.
Embodiment 5
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg beta-schardinger dextrin-in 15ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out, its drug concentration is 0.33mg/ml, Fig. 6 is to implement the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion that 5 examples prepare, granule is irregular lamellar, and mean diameter is 347nm
Embodiment 6
1) weigh 45mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg hydroxypropyl methyl cellulose in 15ml deionized water, pour into during collection burns, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, it is 0.33mg/ml that aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out its drug concentration, Fig. 7 is to implement the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion that 6 examples prepare, and granule cannot nucleation.
Embodiment 7
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg polyvinylpyrrolidone in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 18 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 120 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, it is 1mg/ml that aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out its drug concentration, and nano-particle mean diameter is 284nm.
Embodiment 8
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg polyvinylpyrrolidone in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 18 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, it is 1mg/ml that aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out its drug concentration, and nano-particle mean diameter is 180nm.
Embodiment 9
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg polyvinylpyrrolidone in 5ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, it is 1mg/ml that aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out its drug concentration, Fig. 8 is to implement the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion that 9 examples prepare, and mean diameter is 124nm.
Embodiment 10
1) weigh 50mg beclometasone and 50ml deionized water, be simultaneously introduced in reactor；
2) weighing 7.5mg polyvinylpyrrolidone in 15ml deionized water, pour in collection beaker, the beaker that will be equipped with this aqueous solution is placed in ice-water bath, and controlling bath temperature is 0 DEG C, and stir speed (S.S.) is 800rpm.
3) experimental provision is after air-leakage test, controls system temperature by heater and is increased to 140 DEG C, N2It is passed in the middle of reaction unit by high-pressure pump and makes whole experimental provision boost in pressure to 6MPa in 5min, adjusting high-pressure pump makes whole experimental provision pressure keep constant, after system stability, open the agitating device in reactor, regulation mixing speed is 160r/min, and stirring 20min makes system reach dissolution equilibrium；
4) the subcritical water solution dissolved with beclometasone is ejected into step 2) collection beaker in, it is 1mg/ml that aqueous phase i.e. has beclometasone nanoparticle precipitate to separate out its drug concentration, Fig. 9 is to implement the scanning electron microscope (SEM) photograph of granule in the beclometasone Nanodispersion that 10 examples prepare, granule is unifonn spherical, particle diameter narrow distribution, mean diameter is 78nm.
Gained beclometasone Nanodispersion contrasts with water, it can be seen that Nanodispersion transparency is close with water, and stable in properties.
The bright Nanodispersion of propanoic acid times chlorine that Figure 10 is beclometasone crude drug Dissolution profiles figure in aqueous and embodiment 10 prepares Dissolution profiles figure in aqueous, as can be seen from Figure 10, in 20min, the only dissolution 10.54% of beclometasone crude drug powder body, beclometasone Nanodispersion then dissolution 49.95%, it it is 5 times of crude drug dissolution rate, when the time arrives 120min, beclometasone Nanodispersion dissolution is 94.57%, the most almost it is completely dissolved, and crude drug only dissolution 20.89%.Figure 11 is beclometasone Nanodispersion and the XRD figure of crude drug powder body in embodiment 4 and example 10.
Claims (10)
1. the preparation method of a beclometasone transparent nano dispersion, it is characterised in that comprise the steps:
1) appropriate beclometasone and water are added simultaneously in reactor；
2) dispersant is dissolved in water, the adjuvant aqueous solution being configured to, and control aqueous temperature at 0-20 DEG C, stir speed (S.S.)
For 600-800rpm；
3) in reactor, N it is passed through2Gas, regulation system temperature value preset temperature, regulation reaction system pressure reaches to preset pressure
Power；
4) after balance to be dissolved, being sprayed into rapidly by liquid in reactor dissolved with in the aqueous solution of dispersant, liquid spouting velocity is
5-10ml/min, nano-particle i.e. Precipitation, i.e. obtain transparent aqueous phase Nanodispersion.
Preparation method the most according to claim 1, it is characterised in that: step 1) described beclometasone quality is
18-50mg, the volume of water is 40-60ml.
Preparation method the most according to claim 1, it is characterised in that: step 2) described dispersant concentration in water is
0.1-5mg/ml, dispersant is selected from Polyethylene Glycol, beta-schardinger dextrin-, hydroxypropyl methyl cellulose and polyvinylpyrrolidone.
Preparation method the most according to claim 1, it is characterised in that: step 3) the default pressure of reaction kettle for reaction system
Power is 6-8MPa, and reaction temperature is 120-160 DEG C, and stir speed (S.S.) is 150-200rpm, reaches the dissolution equilibrium time and is
10-20min。
Preparation method the most according to claim 1, it is characterised in that: step 4) described) reactor ejection propanoic acid times chlorine
Rice pine aqueous solution volume is 5-10ml, and the volume of adjuvant aqueous solution is 10-50ml.
Preparation method the most according to claim 1, it is characterised in that: step 4) adjuvant aqueous temperature is 0-18 DEG C,
Rotating speed 400-500rpm.
The preparation method of beclometasone transparent aqueous phase Nanodispersion the most according to claim 1, it is characterised in that:
Reactor is vertical closing container in step 1, is arranged on the filter in the middle part of reactor and is connected in probe tube, filters
The aperture of device is 500 nanometers.
The preparation method of beclometasone transparent aqueous phase Nanodispersion the most according to claim 1, it is characterised in that:
In step 3 by the subcritical water dissolved with beclometasone through filter, it is ejected in nano-particle catcher, dimension
Hold catcher temperature constant, make the rapid crystallization nucleation of nano-particle, accelerate particles collision by two-forty stirring, form nanometer
Granule.
9. the beclometasone nano-particle prepared according to preparation method described in claim 1-6, it is characterised in that: described
The particle diameter of beclometasone rice grain is 40-90nm；The dissolution rate of the granule in described beclometasone Nanodispersion
For dissolution 92.9%-94.6% in 120min, faster than the dissolution rate of crude drug powder body 5-10 times.
Preparation method the most according to claim 9, it is characterised in that: described propanoic acid cup chlorine rice pine transparent aqueous phase nanometer is divided
The concentration of a prose style free from parallelism is 0.1-2mg/ml.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108175764A (en) * | 2017-12-19 | 2018-06-19 | 亿腾医药（苏州）有限公司 | A kind of anhydrous beclomethasone dipropionate aseptic powdery and its preparation method for sucking suspension |
| CN115414321A (en) * | 2022-10-20 | 2022-12-02 | 山东新时代药业有限公司 | Beclomethasone dipropionate emulsifiable paste and preparation method thereof |
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| WO1993017665A1 (en) * | 1992-03-06 | 1993-09-16 | Sievers Robert E | Methods and apparatus for drug delivery using supercritical solutions |
| CN102188372A (en) * | 2010-03-12 | 2011-09-21 | 北京化工大学 | Medicinal transparent nano dispersant and preparation method thereof |
| WO2014006254A1 (en) * | 2012-07-03 | 2014-01-09 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii | Nanoparticles coated with gelatin |
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2015
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| WO1993017665A1 (en) * | 1992-03-06 | 1993-09-16 | Sievers Robert E | Methods and apparatus for drug delivery using supercritical solutions |
| CN102188372A (en) * | 2010-03-12 | 2011-09-21 | 北京化工大学 | Medicinal transparent nano dispersant and preparation method thereof |
| WO2014006254A1 (en) * | 2012-07-03 | 2014-01-09 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii | Nanoparticles coated with gelatin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108175764A (en) * | 2017-12-19 | 2018-06-19 | 亿腾医药（苏州）有限公司 | A kind of anhydrous beclomethasone dipropionate aseptic powdery and its preparation method for sucking suspension |
| CN108175764B (en) * | 2017-12-19 | 2020-02-21 | 亿腾医药（苏州）有限公司 | Preparation method of anhydrous beclomethasone dipropionate sterile powder and inhalation suspension thereof |
| CN115414321A (en) * | 2022-10-20 | 2022-12-02 | 山东新时代药业有限公司 | Beclomethasone dipropionate emulsifiable paste and preparation method thereof |
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