CN106924190A - A kind of ACT-064992 microballoon and preparation method thereof - Google Patents
A kind of ACT-064992 microballoon and preparation method thereof Download PDFInfo
- Publication number
- CN106924190A CN106924190A CN201511005211.5A CN201511005211A CN106924190A CN 106924190 A CN106924190 A CN 106924190A CN 201511005211 A CN201511005211 A CN 201511005211A CN 106924190 A CN106924190 A CN 106924190A
- Authority
- CN
- China
- Prior art keywords
- act
- microballoon
- oil phase
- aqueous solution
- stabilizer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Abstract
The invention provides a kind of ACT-064992 microball preparation and preparation method thereof.ACT-064992 microballoon of the invention includes ACT-064992, polymer carrier materials, emulsifying agent and stabilizer.The preparation method of ACT-064992 microball preparation of the invention is comprised the following steps:(1) polymer carrier materials and ACT-064992 are dissolved in oil phase solvent, as oil phase;It is water phase with the aqueous solution of emulsifying agent;(2) oil phase is added in the water phase and homogeneity, forms O/W emulsions;(3) emulsion is added into the aqueous solution of stabilizer, oil phase solvent is volatilized completely;(4) microballoon, washing, drying are separated, microball preparation of the invention is obtained final product.
Description
Technical field
The application is related to field of pharmaceutical preparations.Specifically, the present invention relates to a kind of ACT-064992
Microball preparation and preparation method thereof.
Background technology
Pulmonary hypertension refers to that the pulmonary artery pressure that a variety of causes causes persistently increases, and is rare slow
Property syndrome, show as pulmonary artery reduce, damaged and hyperpiesia.Its cause of disease is complicated, examines
Break, treat it is thorny be therapy field slower development for a long time main cause.According to estimates,
Only US and European just has 130,000 patients with pulmonary hypertension.In China, because population base is larger,
Paathogenic factor is more, and the incidence of disease of pulmonary hypertension is underestimated significantly.If patient is in pulmonary artery
High pressure does not obtain the effective treatment in postictal 2 years, and its survival rate is only 40%-55%.
ACT-064992 is a kind of Endothelin (endothelin, ET) that Actelion drugmakers develop
Receptor antagonist, can suppress the vessel retraction caused by Endothelin, to ETA acceptors, ETB
There is acceptor double inhibition to act on, and can be used to treat the diseases such as pulmonary hypertension, lung fiber.Horse
West is C for smooth molecular formula19H20Br2N6O4S, chemical name:N- [5- (4- bromophenyls) -6- [2- [(5-
Bromo- 2- pyrimidine radicals) oxygen] ethyoxyl] -4- pyrimidine radicals]-N '-sulfonyl propyl amine, structure such as formula (I) institute
Show:
Existing ACT-064992 piece (trade name Opsumit), its specification is 10mg/ pieces, daily clothes
With once.Clinical studies show, observes most common bad in patient is treated with Opsumit
Reaction (than placebo more frequency 3% or more) have anaemia, nasopharyngitis/pharyngitis, bronchitis,
Headache, influenza and urethral infection.Used as endothelin-receptor antagonists, ACT-064992 is by oral administration
Also there is hepatotoxicity wind agitation, embryo's fetotoxicity equivalent risk after administration.
There are some researches show, particle diameter in 7-30 μm of microballoon after intravenous injection, can be by
PC bed mechanicalness leaching, so as to have lung targeted characteristic.Therefore, in order to reduce Ma Xi
Side effect for smooth makes gained micro-, it is necessary to develop a kind of method for preparing ACT-064992 microballoon
The average grain diameter of ball is in the range of 7-30 μm.
The content of the invention
The present inventor proposes a kind of side for preparing ACT-064992 microball preparation by research
Method.
The method for preparing ACT-064992 microball preparation of the invention, comprises the following steps:
(1) polymer carrier materials and ACT-064992 are successively dissolved in oil phase solvent, as oil phase;
Using the aqueous solution of emulsifying agent as water phase;
(2) at room temperature, the oil phase is added in the water phase and carries out homogeneity, formed
O/W emulsions;
(3) the O/W emulsions are added into the aqueous solution of stabilizer, is stirred, make oil phase
Solvent volatilizees completely;
(4) centrifugation microballoon, and with distillation water washing, dry.
Correspondingly, the present invention also provides the ACT-064992 microball preparation prepared according to the above method.
Brief description of the drawings
Fig. 1 shows the grain size distribution of the ACT-064992 microballoon of embodiment 1.
Fig. 2 shows the grain size distribution of the ACT-064992 microballoon of embodiment 2.
Fig. 3 shows the grain size distribution of the ACT-064992 microballoon of embodiment 3.
Fig. 4 shows the grain size distribution of the ACT-064992 microballoon of embodiment 4.
Fig. 5 shows the grain size distribution of the ACT-064992 microballoon of embodiment 5.
Fig. 6 shows the grain size distribution of the ACT-064992 microballoon of embodiment 6.
Fig. 7 shows the grain size distribution of the ACT-064992 microballoon of embodiment 7.
Fig. 8 shows the grain size distribution of the ACT-064992 microballoon of embodiment 8.
Fig. 9 shows the grain size distribution of the ACT-064992 microballoon of embodiment 9.
Figure 10 shows the grain size distribution of the ACT-064992 microballoon of embodiment 10.
Figure 11 shows the grain size distribution of the ACT-064992 microballoon of embodiment 11.
Figure 12 shows the vitro release of the ACT-064992 microball preparation of embodiment 2 with the time
The curve of change.
Specific embodiment
The present invention provides a kind of method for preparing ACT-064992 microball preparation, comprises the following steps:
(1) polymer carrier materials and ACT-064992 are successively dissolved in oil phase solvent, as oil phase
(dispersed phase);Using the aqueous solution of emulsifying agent as water phase (continuous phase);
(2) at room temperature, the oil phase is added in the water phase and carries out homogeneity, formed
O/W emulsions;
(3) the O/W emulsions are added into the aqueous solution of stabilizer, is stirred, make oil phase
Solvent volatilizees completely;
(4) centrifugation microballoon, and with distillation water washing, dry.
In the context of the present invention, the polymer carrier materials refer to conventional biodegradable
Polymeric material, including but not limited to Poly(D,L-lactide-co-glycolide (PLGA), PLA
(PLA), polyglycolic acid (PGA), polycaprolactone (PCL) or PTMC
(PTMC), most preferably Poly(D,L-lactide-co-glycolide.
In the context of the present invention, the oil phase solvent generally has the following properties that:(1) can be molten
Depolymerization compound;(2) solubility in continuous phase is small;(3) with vapour pressure and low boiling high
Point;(4) small toxicity.Herein, the oil phase solvent refers generally to organic solvent, including but
Be not limited to dichloromethane, acetone, ethyl acetate, or above-mentioned any two kinds of solvents mixture,
Most preferably dichloromethane.
In the context of the present invention, the emulsifying agent is hard selected from polyvinyl alcohol (PVA), glycerine
Resin acid ester, polyethylene glycol (PEG) oleate and Tween-80, most preferably polyvinyl alcohol.
In the context of the present invention, the stabilizer is selected from polyvinylpyrrolidone (PVP)
Or polyvinyl alcohol, preferred polyvinylpyrrolidone.
In a preferred embodiment of the invention, wherein in step (2), oil phase and water
The volume ratio of phase is 1: 1 to 1: 40, preferably 1: 5 to 1: 30, most preferably 1: 15.
In a preferred embodiment of the invention, wherein in step (2), homogeneity exists
Carried out under 6000-12000rpm, preferably 7000-10000rpm, most preferably 8500rpm.
In a preferred embodiment of the invention, wherein in step (3), the poly- second
The mass concentration of the alkene pyrrolidone aqueous solution is 0.01% to 0.5%, preferably 0.01 to 0.3%,
Most preferably 0.1%.
Correspondingly, the present invention also provide it is a kind of by the method for the present invention prepare ACT-064992 it is micro-
Ball preparation, it is characterised in that the particle diameter of at least 80% ACT-064992 microballoon is at 7-30 μm
In the range of.
In a preferred embodiment of the invention, ACT-064992 microball preparation of the invention
Drugloading rate is 1%-7%, preferably 2%-5%, most preferably 3%-4.5%.
In a preferred embodiment of the invention, ACT-064992 microball preparation of the invention
Envelop rate is more than 60%, preferably more than 70%, more preferably more than 80%, most preferably 90%
More than.
Embodiment
The present invention is described in further detail with reference to embodiments.Following examples should not
It is interpreted limitation of the present invention.All technologies realized based on present invention belong to this
The scope of invention.
Embodiment 1
Drug bearing microsphere is prepared using emulsification-evaporation method.Weigh 600mg PLGA and 30mg
ACT-064992 is dissolved in 2.82g dichloromethane, as oil phase, is with the 0.5%PVA aqueous solution
, be added to oil phase in water phase with 1: 15 ratio at room temperature by water phase, high with 7000rpm
Speed shearing 120s, forms O/W emulsions.Gained O/W emulsions are added to volume ratio 1: 3
In the 0.1%PVP aqueous solution of stirring, continue to stir 3h, dichloromethane is fully volatilized,
Obtain ACT-064992 microballoon of the invention.ACT-064992 microballoon described in subsequent centrifugation, with steaming
After distilled water washs 3 times, dry.
It is determined by the following procedure envelop rate, drugloading rate and the particle diameter of thus obtained microsphere.
Microballoon 5mg is weighed, in 15mL centrifuge tubes, 0.5mL dichloromethane is added, surpassed
Sound dissolves microballoon, adds 2.5mL methyl alcohol, vortex 10min, 11000r/min centrifugation
10min, takes supernatant.The content of ACT-064992 in microballoon is determined with HPLC.
Drugloading rate=(ACT-064992 quality/microballoon gross mass in microballoon) × 100%
Envelop rate=(ACT-064992 quality/input ACT-064992 gross mass in microballoon) × 100%
Microballoon is dispersed in pure water, detects that microballoon is average with laser particle analyzer after ultrasonic disperse
Particle diameter and particle diameter distribution.
After measured, the envelop rate of thus obtained microsphere is 88.92%, drugloading rate 4.02%, average grain diameter
It is 23.5 μm, and 80.2% microspherulite diameter is distributed in 7~30 μm, particle diameter distribution is shown in Fig. 1.
Embodiment 2:
Drug bearing microsphere is prepared according to the same manner as in Example 1, except shear rate is 8500
rpm.After measured, the envelop rate of thus obtained microsphere is 93.76%, drugloading rate 4.37%, average grain
Footpath is 16.8 μm, and 91.6% microspherulite diameter is distributed in 7~30 μm, and particle diameter distribution is shown in Fig. 2.
Embodiment 3:
Drug bearing microsphere is prepared according to the same manner as in Example 1, except shear rate is 10000
rpm.After measured, the envelop rate of thus obtained microsphere is 85.76%, drugloading rate 4.15%, average grain
Footpath is 11.6 μm, and 86.3% microspherulite diameter is distributed in 7~30 μm, and particle diameter distribution is shown in Fig. 3.
The size that can be seen that shear rate from the result of embodiment 1-3 influences the particle diameter of microballoon:
In the range of 7000rpm-10000rpm, shear rate is bigger, and microspherulite diameter diminishes therewith.
Most preferably, shear rate is 8500rpm.
Embodiment 4:
Drug bearing microsphere is prepared according to the same manner as in Example 2, except profit Phase Proportion is 1: 8.
After measured, the envelop rate of thus obtained microsphere is 86.76%, drugloading rate 4.00%, and average grain diameter is
12.9 μm, and 84.5% of microspherulite diameter is distributed in 7~30 μm, and particle diameter distribution is shown in Fig. 4.
Embodiment 5:
Drug bearing microsphere is prepared according to the same manner as in Example 2, except profit Phase Proportion is 1: 25.
After measured, the envelop rate of thus obtained microsphere is 89.76%, drugloading rate 4.22%, and average grain diameter is
24.9 μm, and 82.5% of microspherulite diameter is distributed in 7~30 μm, and particle diameter distribution is shown in Fig. 5.
The result of embodiment 4 and 5 shows, as water phase volume increases, microspherulite diameter is also therewith
Become big.
Embodiment 6:
PLGA is replaced with PCL, drug bearing microsphere is prepared with method same as Example 2.Through
Determine, the envelop rate of thus obtained microsphere is 73.76%, and drugloading rate 3.32%, average grain diameter is 13.4
μm, and 80.9% microspherulite diameter is distributed in 7~30 μm, particle diameter distribution is shown in Fig. 6.
Embodiment 7:
Using acetone as organic phase, drug bearing microsphere is prepared for the identical method of embodiment 2.Through
Determine, the envelop rate of thus obtained microsphere is 63.15%, and drugloading rate 3.17%, average grain diameter is 12.7
μm, and 86.5% microspherulite diameter is distributed in 7~30 μm, particle diameter distribution is shown in Fig. 7.
Embodiment 8:
With 0.5% glycerol stearate aqueous solution of ester as emulsifying agent, with same as Example 2
Method prepares drug bearing microsphere.After measured, the envelop rate of thus obtained microsphere is 83.76%, drugloading rate
3.96%, average grain diameter is 27.7 μm, and the microspherulite diameter for having 55.6% is distributed in 7~30 μm,
Particle diameter distribution is shown in Fig. 8.
Embodiment 9:
Replace the 0.1%PVP aqueous solution with the 0.1%PVA aqueous solution as stabilizer, with implementation
The identical method of example 2 prepares drug bearing microsphere.After measured, resulting microsphere encapsulation rate is 86.22%,
Drugloading rate 4.25%, average grain diameter is 29.8 μm, and the microspherulite diameter for having 45.6% is distributed in 7~30
μm, particle diameter distribution is shown in Fig. 9.
Embodiment 10:
Drug bearing microsphere is prepared according to the same manner as in Example 2, except stabilizer PVP concentration is
0.01%.After measured, resulting microsphere encapsulation rate is 90.20%, drugloading rate 4.17%, averagely
Particle diameter is 22.5 μm, and the microspherulite diameter for having 84.6% is distributed in 7~30 μm, and particle diameter distribution is shown in figure
10。
Embodiment 11:
Drug bearing microsphere is prepared according to the same manner as in Example 2, except stabilizer PVP concentration is
0.3%.After measured, resulting microsphere encapsulation rate is 89.23%, drugloading rate 4.21%, average grain
Footpath is 18.8 μm, and the microspherulite diameter for having 88.9% is distributed in 7~30 μm, and particle diameter distribution is shown in Figure 11.
Embodiment 12:The measure of release
ACT-064992 microball preparation using embodiment 2 as sample, after precision weighs freeze-drying
ACT-064992 microball preparation, 37.5 DEG C are added to, in the phosphate buffer of pH 7.4, in perseverance
Shaken with the speed of 100rpm in warm oscillator, respectively at 1,2,4,8,12,24,48,
72nd, 96,144,168h samplings, and the Isothermal release medium of same volume is supplemented after sampling.
Drug accumulation burst size (being shown in Table 1) is detected with high performance liquid chromatography, microballoon release in vitro is drawn
The curve (Figure 12) for changing over time.
Table 1:The external releasing result of ACT-064992 microballoon
Claims (10)
1. a kind of method for preparing ACT-064992 microballoon, comprises the following steps:
(1) polymer carrier materials and ACT-064992 are successively dissolved in oil phase solvent, as oil phase;
Using the aqueous solution of emulsifying agent as water phase;
(2) at room temperature, the oil phase is added in the water phase and carries out homogeneity, formed
O/W emulsions;
(3) the O/W emulsions are added into the aqueous solution of stabilizer, is stirred, make oil phase molten
Agent is volatilized completely;
(4) microballoon described in centrifugation, and with distillation water washing, dry.
2. method according to claim 1, wherein the polymer carrier materials are can be biological
The macromolecular material of degraded, preferably Poly(D,L-lactide-co-glycolide, PLA, polyglycolic acid,
Polycaprolactone or PTMC, most preferably Poly(D,L-lactide-co-glycolide.
3. method according to claim 1, wherein the oil phase solvent is dichloromethane, third
Ketone, ethyl acetate, or above-mentioned any two kinds of solvents mixture, most preferably dichloromethane.
4. method according to claim 1, wherein the emulsifying agent is polyvinyl alcohol, glycerine
Stearate, polyethylene glycol (PEG) oleate, Tween-80, most preferably polyvinyl alcohol;The stabilizer
It is polyvinylpyrrolidone or polyvinyl alcohol, preferably polyvinylpyrrolidone.
5. method according to claim 1, wherein in step (2), the oil phase with
The volume ratio of the water phase is 1: 1 to 1: 40, preferably 1: 5 to 1: 30, most preferably 1: 15.
6. method according to claim 1, wherein in step (2), the homogeneity
Carried out under 6000-12000rpm, most preferably preferably 7000-10000rpm, 8500rpm.
7. the method according to claim any one of 1-6, wherein the polyvinylpyrrolidone
The mass concentration of the aqueous solution is 0.01% to 0.5%, preferably 0.01 to 0.3%, most preferably 0.1%.
8. a kind of ACT-064992 microball preparation, it includes ACT-064992, polymer carrier materials, breast
Agent and stabilizer, wherein, the average grain diameter of the ACT-064992 microballoon is 10-30 μm, and extremely
The particle diameter of few 40% ACT-064992 microballoon is in the range of 7-30 μm;The ACT-064992 microballoon
Drugloading rate be 1%-7%, envelop rate be more than 60%.
9. ACT-064992 microball preparation according to claim 8, it is characterised in that the horse
West is preferably 2%-5%, most preferably 3%-4.5% for the drugloading rate of smooth microballoon.
10. ACT-064992 microball preparation according to claim 8, it is characterised in that described
The envelop rate of ACT-064992 microballoon is preferably more than 70%, more preferably more than 80%, most preferably 90%
More than.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511005211.5A CN106924190A (en) | 2015-12-30 | 2015-12-30 | A kind of ACT-064992 microballoon and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511005211.5A CN106924190A (en) | 2015-12-30 | 2015-12-30 | A kind of ACT-064992 microballoon and preparation method thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106924190A true CN106924190A (en) | 2017-07-07 |
Family
ID=59458025
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201511005211.5A Pending CN106924190A (en) | 2015-12-30 | 2015-12-30 | A kind of ACT-064992 microballoon and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106924190A (en) |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101292960A (en) * | 2006-04-29 | 2008-10-29 | 中国人民解放军军事医学科学院毒物药物研究所 | Sustained-release microsphere containing risperidone and preparation method thereof |
CN101428142A (en) * | 2007-11-08 | 2009-05-13 | 江苏先声药物研究有限公司 | Process for producing recombinant human vascular endothelial inhibitor composition sustained-release microsphere |
CN101658496A (en) * | 2009-09-11 | 2010-03-03 | 中国人民解放军第二军医大学 | Exenatide release microsphere preparation, preparation method and application thereof |
CN101756910A (en) * | 2010-03-18 | 2010-06-30 | 青岛康地恩药业有限公司 | Lung targeting ceftiofur microsphere and preparation method |
CN102188384A (en) * | 2011-04-28 | 2011-09-21 | 上海交通大学 | Microsphere preparation method for adjusting and controlling release behavior of risperidone microspheres and for controlling size thereof |
CN103142488A (en) * | 2011-12-16 | 2013-06-12 | 深圳市健元医药科技有限公司 | GLP-I analogue liraglutide sustained-release microspheres and preparation method thereof |
CN104411691A (en) * | 2013-06-14 | 2015-03-11 | 杭州普晒医药科技有限公司 | Macitentan crystal, preparation method therefor, pharmaceutical composition and use thereof |
CN104447572A (en) * | 2014-12-15 | 2015-03-25 | 南京艾德凯腾生物医药有限责任公司 | Method for preparing macitentan |
CN105030692A (en) * | 2015-07-13 | 2015-11-11 | 青岛农业大学 | Lung-targeted PLGA (polylactic-co-glycolic-acid) microsphere preparation of cefquinome sulfate and preparation method of lung-targeted PLGA microsphere preparation |
CN105106174A (en) * | 2015-09-06 | 2015-12-02 | 烟台大学 | Core-shell bilayer microsphere and preparation method thereof |
CN105147640A (en) * | 2015-08-06 | 2015-12-16 | 合肥华方医药科技有限公司 | Total bufogenin PLGA nanoparticle freeze-drying preparation and preparation method thereof |
ES2584534A1 (en) * | 2015-03-27 | 2016-09-28 | Retinset, S.L. | Ophthalmic topical formulation of bosentan (Machine-translation by Google Translate, not legally binding) |
-
2015
- 2015-12-30 CN CN201511005211.5A patent/CN106924190A/en active Pending
Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101292960A (en) * | 2006-04-29 | 2008-10-29 | 中国人民解放军军事医学科学院毒物药物研究所 | Sustained-release microsphere containing risperidone and preparation method thereof |
CN101428142A (en) * | 2007-11-08 | 2009-05-13 | 江苏先声药物研究有限公司 | Process for producing recombinant human vascular endothelial inhibitor composition sustained-release microsphere |
CN101658496A (en) * | 2009-09-11 | 2010-03-03 | 中国人民解放军第二军医大学 | Exenatide release microsphere preparation, preparation method and application thereof |
CN101756910A (en) * | 2010-03-18 | 2010-06-30 | 青岛康地恩药业有限公司 | Lung targeting ceftiofur microsphere and preparation method |
CN102188384A (en) * | 2011-04-28 | 2011-09-21 | 上海交通大学 | Microsphere preparation method for adjusting and controlling release behavior of risperidone microspheres and for controlling size thereof |
CN103142488A (en) * | 2011-12-16 | 2013-06-12 | 深圳市健元医药科技有限公司 | GLP-I analogue liraglutide sustained-release microspheres and preparation method thereof |
CN104411691A (en) * | 2013-06-14 | 2015-03-11 | 杭州普晒医药科技有限公司 | Macitentan crystal, preparation method therefor, pharmaceutical composition and use thereof |
CN104447572A (en) * | 2014-12-15 | 2015-03-25 | 南京艾德凯腾生物医药有限责任公司 | Method for preparing macitentan |
ES2584534A1 (en) * | 2015-03-27 | 2016-09-28 | Retinset, S.L. | Ophthalmic topical formulation of bosentan (Machine-translation by Google Translate, not legally binding) |
CN105030692A (en) * | 2015-07-13 | 2015-11-11 | 青岛农业大学 | Lung-targeted PLGA (polylactic-co-glycolic-acid) microsphere preparation of cefquinome sulfate and preparation method of lung-targeted PLGA microsphere preparation |
CN105147640A (en) * | 2015-08-06 | 2015-12-16 | 合肥华方医药科技有限公司 | Total bufogenin PLGA nanoparticle freeze-drying preparation and preparation method thereof |
CN105106174A (en) * | 2015-09-06 | 2015-12-02 | 烟台大学 | Core-shell bilayer microsphere and preparation method thereof |
Non-Patent Citations (4)
Title |
---|
中国核学会: "《中国核科学技术进展报告 中国核学会2009年学术年会论文集•第1卷 第8册》", 30 November 2010 * |
中国生物医学工程学会: "《第四次全国生物医学工程学术会议论文汇编》", 31 December 1990 * |
时钧等: "《膜技术手册》", 31 January 2001, 化学工业出版社 * |
湖北大学学位办: "《湖北大学硕士学位论文摘要汇编 2002年卷》", 31 December 2002 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Rai et al. | Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon | |
JP5587198B2 (en) | Freeze-dried pharmaceutical composition having improved stability, containing taxane derivative, and method for producing the same | |
De La Ossa et al. | Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: Development, characterization and in vitro evaluation of their antitumoral efficacy | |
Ilevbare et al. | Effect of binary additive combinations on solution crystal growth of the poorly water-soluble drug, ritonavir | |
Kim et al. | Fabrication and evaluation of valsartan–polymer–surfactant composite nanoparticles by using the supercritical antisolvent process | |
Wang et al. | Preparation and evaluation of curcumin-loaded self-assembled micelles | |
Ahmed et al. | Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior | |
Gungor et al. | Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes | |
CN108079308B (en) | Coenzyme Q10Nano-structure lipid carrier compounded with octacosanol and preparation method thereof | |
CN104906044B (en) | A kind of deccox nanometer formulation and the preparation method and application thereof | |
Yousaf et al. | Influence of polyvinylpyrrolidone quantity on the solubility, crystallinity and oral bioavailability of fenofibrate in solvent-evaporated microspheres | |
Birer et al. | Electrospun orally disintegrating film formulation of telmisartan | |
Sharma et al. | Supersaturation-based drug delivery systems: strategy for bioavailability enhancement of poorly water-soluble drugs | |
Rimkiene et al. | Development and evaluation of Ginkgo biloba L. Extract loaded into carboxymethyl cellulose sublingual films | |
Li et al. | Development and evaluation of optimized sucrose ester stabilized oleanolic acid nanosuspensions prepared by wet ball milling with design of experiments | |
CN106511348B (en) | Huperzine skeleton particle, oral disintegrating tablet and preparation method thereof | |
CN103585113B (en) | Apigenin polylactic acid sustained release microsphere and preparation method thereof | |
Zhang et al. | Nanoemulsion formulation of florfenicol improves bioavailability in pigs | |
CN106983719A (en) | A kind of docetaxel polymer nano micelle injection, its preparation method and its application in tumor is prepared | |
CN102579365B (en) | Risperidone microsphere preparation and preparation method thereof | |
CN104434797B (en) | A kind of Florfenicol solid self-emulsifying preparation | |
Rajesh et al. | Feasibility of xanthan gum–sodium alginate as a transdermal drug delivery system for domperidone | |
CN106924190A (en) | A kind of ACT-064992 microballoon and preparation method thereof | |
CN106070221A (en) | A kind of Fluoxastrobin microsphere and preparation method thereof | |
Yang et al. | Preparation and evaluation of posaconazole-loaded enteric microparticles in rats |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170707 |