CN105581996B - A kind of dianhydrogalactitol micro-capsule and preparation method thereof - Google Patents
A kind of dianhydrogalactitol micro-capsule and preparation method thereof Download PDFInfo
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- CN105581996B CN105581996B CN201610098241.3A CN201610098241A CN105581996B CN 105581996 B CN105581996 B CN 105581996B CN 201610098241 A CN201610098241 A CN 201610098241A CN 105581996 B CN105581996 B CN 105581996B
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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
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
-
- 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
- A61K9/5015—Organic compounds, e.g. fats, sugars
Abstract
The present invention discloses a kind of dianhydrogalactitol micro-capsule and preparation method thereof.The microcapsule formulation prescription is mainly：Dianhydrogalactitol, polyacrylic resinⅢ, diethyl phthalate, castor oil, mannitol；Result of the test shows that the present invention prepares gained microcapsule granule rounding, and grain is passed through at 45 100 μm, and for envelop rate more than 80%, drugloading rate reaches 30.2 35.8%.Stability is higher.
Description
Technical field
The present invention relates to field of medicine invention, more particularly to a kind of composition of dianhydrogalactitol micro-capsule and its preparation side
Method.
Background technology
Chronic myelocytic leukemia (ChronicMyelogenousLeukemia, CML) is a kind of influence blood and marrow
Malignant tumour, its notable feature is the excessive generation of granulocyte in marrow and peripheral blood.Remove allogeneic hematopoietic stem cell at present
Transplanting is outer, there is no radical cure method, and Allogeneic Bone Marrow Transplantation is the healing most promising therapies of CML, but its success rate so far
Only 33% or so, and costly reach hundreds thousand of, the generally powerless burden of patient.Therefore, clinically main treatment means, it is still
After radiotherapy or chemotherapy, alleviated conditions of patients by drug therapy.
Dianhydrogalactitol (the entitled 1,2,5,6- two to the water wei ling alcohol of chemistry) is the bicyclic oxidation of mitolactol hydrogen bromide
Thing, it is white column, flaky crystal or crystalline powder, odorless, slight bitter is soluble in water, in ethanol, acetone, ethyl acetate
Dissolving；It is hexasaccharide cancer therapy drug, while has cross resistance with alkylating agent, can also be classified as alkylating agents, but it acts on machine
System can not be explained with this completely.Through consulting literatures understand, dianhydrogalactitol (DAG) can by with the GGCC sequences on DNA
With reference to induced DNA fragmentation, so as to produce antitumor action；DAG can suppress the synthesis of the large biological molecules such as nucleic acid and albumen, to dynamic
Thing transplanted tumor has the antitumor action of wide spectrum；Show simultaneously through clinical trial, DAG has preferably to chronic myelocytic leukemia
Short term effect, remission rate is and effective very fast up to 86%, and drug combination can produce synergy, and can be right by blood-brain barrier
Blood vessel is non-stimulated, to the harmless effect of hepatic and renal function.This can not compare for some other common cancer therapy drug.Water is gone to defend
Lance alcohol structural formula is as follows：
Dianhydrogalactitol category intravenous injection at present, compliance is low, if decoction exosmoses during injection, may cause local organization
Necrosis, forms ulcer, should prevent decoction from exosmosing during use；Simultaneously by analyzing its chemical formula, dianhydrogalactitol is extremely unstable
Fixed, oxirane is easily reduced open loop and loses alkylating, so as to which activity reduces.Therefore searching one kind is needed to carry at present
The method of high dianhydrogalactitol compliance and stability.
The content of the invention
It is an object of the invention to provide a kind of dianhydrogalactitol micro-capsule.
It is a further object to provide a kind of preparation method of dianhydrogalactitol micro-capsule.
Because existing dianhydrogalactitol is injecting drug use, the problems such as the forming ulcer that have that medication is inconvenient, decoction exosmoses,
Accordingly, it is desirable to provide a kind of product for being convenient for carrying and using, increases medicine-feeding way, meets the market requirement.Through experimental study table
It is bright, after dianhydrogalactitol is made into micro-capsule, its stability, and process stabilizing are not only increased, cost is low, can be made into a variety of mouths
Formulation, convenient drug administration, preferably improve the compliance of patient.
Inventor has found that dianhydrogalactitol micro-capsule is gathered using common capsule material such as gelatin, Arabic gum, shell under study for action
During the materials such as sugar, alginate, due to above material, i.e. all dissolvings in stomach, discharge dianhydrogalactitol, dianhydrogalactitol
Oxirane is easily reduced open loop and loses alkylating under intestines and stomach enzyme system, so as to lose activity.It is combined to go water to defend
The interior environment of the digested absorption of medicinal property, human body and the property of capsule material of lance alcohol, after repetition test, it have finally chosen enteric solubility
Polyacrylic resinⅢ and diethyl phthalate mixture as the capsule material for removing water lance alcohol.Polyacrylic resinⅢ with
Diethyl phthalate is a kind of poly-compounds more sensitive to pH, be our experiments show that, polyacrylic resinⅢ and neighbour
Diethyl phthalate just dissolves in pH ＞ 7, can discharge medicine by privileged site in alimentary canal as capsule material, reduce intestines and stomach
Enzyme system is advantageous to improve the bioavilability of medicine to the metabolism of medicine.
When preparing dianhydrogalactitol micro-capsule, if incomplete without plasticizer, finished product cyst wall partial crushing, parcel；Pass through measure
Elongation degree ε during fractureR(%) judges the compliance of film, our experiments show that, the ε of fat-soluble plasticizer castor oilR＞ 81%, water
The ε of dissolubility plasticizer such as glycerine, PEGRValue is in the range of 34%-53%, in order to what is do not ruptured when obtaining normal operating and storage
Stable film, it is easy to exploitation into more multi-form, therefore it is plasticizer to screen castor oil.Found simultaneously in experimentation, if nonreactive
Agent is adhered, part micro-capsule is adhered conglomeration, anti-stick with magnesium stearate, talcum powder, single stearic acid glycerine lipoprotein, octadecyl alcolol, mannitol etc.
Even agent raw material finds that mannitol can not only overcome the phenomenon that is adhered of micro-capsule, and can improve bag after many experiments are verified
Envelope rate, therefore it is adhered agent as anti-from mannitol.
The present invention is realized by following technical scheme：
The preparation prescription of dianhydrogalactitol microcapsules of the present invention, is made up of the supplementary material of following parts by weight：
1.25~100 parts of dianhydrogalactitol, 5~50 parts of polyacrylic resinⅢ, 3~30 parts of diethyl phthalate, castor oil 1.5
~ 35 parts, 0.08 ~ 25 part of mannitol.
Preferably, it is made up of the supplementary material of following parts by weight：3.75~50 parts of dianhydrogalactitol, polyacrylic resinⅢ
20~35 parts, 12~20 parts of diethyl phthalate, 6~15 parts of castor oil, 4.5~10 parts of mannitol.
Spray drying technology at present turn into medicament microcapsule effective ways, have it is easy to operate, controllability is good, encystation
The features such as rate is high, product is scattered, it is the microencapsulation method of most industrial applications value.When selecting solvent, from removing water winged euonymus
Alcohol chemical property is analyzed, and its is soluble in water, in ethanol, methanol, acetone, ethyl acetate, but because water is in spray drying
It is difficult to volatilize, the micro-capsule of formation is adhered agglomerating；Be present certain toxicity in methanol, ethyl acetate, often occur in spray drying
Dissolvent residual.Through multi-party experimental verification, select concentration for more than 90% ethanol and acetone as solvent.
Dianhydrogalactitol micro-capsule of the present invention is prepared by following steps：
1) take polyacrylic resinⅢ, diethyl phthalate to be dissolved in acetone and capsule material solution is made；
2) take dianhydrogalactitol to be dissolved in ethanol, add in capsule material solution obtained by step 1), add castor oil and sweet dew
It is spray-dried, is produced after alcohol, fully dissolving.
Preferably, the ethanol, concentration of volume percent are not less than 90%.
Dianhydrogalactitol microcapsules provided by the invention has the following advantages：
1st, using spray drying process micro-capsule is made in dianhydrogalactitol by the present invention, with it is easy to operate, controllability is good, into
The features such as capsule rate is high, product is scattered, it is the microencapsulation method of most industrial applications value.
2nd, after micro-capsule is made in dianhydrogalactitol by the present invention, its stability, and process stabilizing, cost are not only increased
It is low, it can be made into several formulations, convenient drug administration, preferably improve the compliance of patient.
3rd, dianhydrogalactitol micro-capsule of the invention privileged site can dissolve in the intestine, discharge medicine, be advantageous to raising and remove water
The bioavilability of dulcitol.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.Wherein plasticizer is adhered with anti-
Agent dosage is to be calculated and obtained on the basis of capsule material dosage, and the concentration that the present invention is indicated is weight volumetric concentration.
Embodiment 1：
Weigh 5kg polyacrylic resinⅢs and 3kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 1.5kg castor oil, 0.8kg
Mannitol, fully dissolving after be spray-dried.
Embodiment 2：
Weigh 50kg polyacrylic resinⅢs and 30kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 100kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 35kg castor oil, 25kg's is sweet
Reveal alcohol, be fully spray-dried after dissolving.
Embodiment 3：
Weigh 20kg polyacrylic resinⅢs and 12kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 3.75kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 6kg castor oil, 4.5kg's
It is spray-dried after mannitol, fully dissolving.
Embodiment 4：
Weigh 35kg polyacrylic resinⅢs and 20kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 50kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 15kg castor oil, 10kg's is sweet
Reveal alcohol, be fully spray-dried after dissolving.
Embodiment 5：
Weigh 25kg polyacrylic resinⅢs and 17kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 10kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 5kg castor oil, 2kg sweet dew
It is spray-dried after alcohol, fully dissolving.
Embodiment 6：
The micro-capsule of gained, encapsulated to produce dianhydrogalactitol capsule in Example 1~5.
Embodiment 7：
The micro-capsule of gained, is suppressed by normal sheeting operation, produces dianhydrogalactitol tablet in Example 1~5.
Comparative example 1：
Weigh 4kg polyacrylic resinⅢs and 3kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 1.5kg castor oil, 0.8kg
Mannitol, fully dissolving after be spray-dried.
Comparative example 2：
Weigh 55kg polyacrylic resinⅢs and 3kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 1.5kg castor oil, 0.8kg
Mannitol, fully dissolving after be spray-dried.
Comparative example 3：
Weigh 5kg polyacrylic resinⅢs and 3kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 1kg castor oil, 0.5kg's
It is spray-dried after mannitol, fully dissolving.
Comparative example 4：
Weigh 5kg polyacrylic resinⅢs and 3kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 37kg castor oil, 26kg's
It is spray-dried after mannitol, fully dissolving.
Comparative example 5：
Weigh 10kg HP55s and be dissolved in 1000L acetone obtained capsule material solution, weigh dianhydrogalactitol
1.25kg is dissolved in a small amount of ethanol, is added in capsule material solution, adds 1.5kg castor oil, fully 0.8kg mannitol, dissolving
After be spray-dried.
Comparative example 6：
Weigh 5kg polyacrylic resinⅢs and 31kg diethyl phthalates and be dissolved in 1000L acetone that capsule material is made is molten
Liquid, weigh dianhydrogalactitol 1.25kg and be dissolved in a small amount of ethanol, be added in capsule material solution, add 1.5kg castor oil, 0.8kg
Mannitol, fully dissolving after be spray-dried.
Quality evaluation is tested：
1st, the measure of the form of micro-capsule, particle diameter, envelop rate and drugloading rate
The assay method of 1.1 envelop rates and drugloading rate：
Actual content of dispersion/reality dispensing total amount × 100% in envelop rate (%)=micro-capsule；
Actual content of dispersion/micro-capsule gross weight × 100% in drugloading rate (%)=micro-capsule.
1.2 forms and Particle Size Determination Method：Using the configuration of surface of SEM (SME) observation micro-capsule, use
Zetasizer laser particle size analyzers determine its particle diameter.
1.3 content assaying method
The preparation of solution：Take dianhydrogalactitol reference substance appropriate, it is accurately weighed, add methanol that about 100 μ g/mL control is made
Product solution.Dianhydrogalactitol micro-capsule about 0.1g is taken, accurately weighed, in 100mL measuring bottles, adding methanol, ultrasonic 1h makes its molten in right amount
Solution, puts to room temperature, adds methanol constant volume to shake up to scale, filter, take subsequent filtrate as need testing solution：With blank micro-capsule by confession
The preparation method of test sample solution prepares negative control solution.
Chromatographic condition：
Chromatographic column：AgilentDB-1 (30m × 0.53mm, 1.5 μm)；
Temperature programming：Initial temperature is 100 DEG C, maintains 3min, rises to 200 DEG C with 10 DEG C/min, maintains 5min；
Injector temperature is 250 DEG C, and detector FID temperature is 250 DEG C；
Carrier gas is nitrogen, flow velocity 5ml/min；Split ratio：1:10；Sampling volume is 1 μ l.
Number of theoretical plate is calculated by dianhydrogalactitol peak is not less than 20000, and the separating degree between dianhydrogalactitol and each impurity is equal
Regulation should be met.
1.4 measurement results are shown in Table 1.
The dianhydrogalactitol micro-capsule form of table 1, particle diameter, entrapment efficiency determination result table
Mode of appearance, envelop rate and the drugloading rate of dianhydrogalactitol micro-capsule, embodiment when the result of table 1 shows different ratio
1-5 preparation prescription can prepare mode of appearance rounding, and envelop rate is higher (equal ＞ 90%), and drugloading rate is good.From comparative example
1st, 3 testing result can see, when the dosage of each auxiliary material component is less than prescription scope of the invention, the form generation of micro-capsule
Change, most surface fractures, envelop rate and drugloading rate reduce.It can see simultaneously from comparative example 2,5, when the content of capsule material is big
When application claims scope, the particle diameter of micro-capsule substantially becomes big, and the situation that part micropill is adhered occurs.Can from comparative example 4
To see, when the content of castor oil and mannitol is higher than scope of the presently claimed invention, micro-capsule surface is glutinous due to being plasticized and resisting
Effect is too strong, causes most surfaces coarse uneven.It can see simultaneously by comparative example 5, when in micro-capsule of the present invention
When capsule material polyacrylic resinⅢ is transformed into polyacrylic resinⅢ with diethyl phthalate, micro-capsule any surface finish, do not stick
Even, envelop rate and drugloading rate meet pharmacopoeial requirements, but particle diameter is excessive does not meet pharmacopoeial requirements.Pass through scanning electron microscopy simultaneously
Mirror (SME) observes the configuration of surface of micro-capsule and determines its particle diameter with Zetasizer laser particle size analyzers, the results showed that embodiment
In the equal form rounding of dianhydrogalactitol micro-capsule, particle diameter is mainly distributed between 45-100 μm.In summary experimental result and point
Analysis obtains, and the preparation prescription composition of dianhydrogalactitol microcapsules of the present invention should be：1.25~100 parts of dianhydrogalactitol,
5~50 parts of polyacrylic resinⅢ, 3~30 parts of diethyl phthalate, castor oil 1.5-35 parts, mannitol 0.08-25 parts.
Wherein optimal prescription is：3.75~50 parts of dianhydrogalactitol, 20~35 parts of polyacrylic resinⅢ, diethyl phthalate 12
~20 parts, castor oil 6-15 parts, mannitol 4.5-10 parts.
2nd, dianhydrogalactitol micro-capsule stability test
2.1 influence factors are tested
Influence factor experiment be than Acceleration study more acutely under conditions of the stability of preparation is detected, this examination
Test mainly with comparative example 1,2,4 for control group, while Example 1-3 carries out influence factor experiment, by observing outward appearance, inspection
Survey weightening, drugloading rate and envelop rate and investigate its stability.
2.1.1 hot test
Dianhydrogalactitol micro-capsule in embodiment is open respectively and is placed in suitable clean container, at 60 DEG C of insulating box,
Place 10 days, sampled in 0 day, 5 days, 10 days, detected by foregoing detection project, the results are shown in Table 2.
The dianhydrogalactitol micro-capsule hot test result of table 2
As seen from the data in Table 2, sample is placed 10 days under the conditions of 60 DEG C, and the sample appearance of comparative example is changed into slightly yellow, is carried
Dose and envelop rate reduce；And the outward appearance of embodiment, drugloading rate, envelop rate are without significant change.Such case occurs in comparative example can
It can be microcapsule wall parts against wear, lose defencive function under the high temperature conditions, second, capsule core material dianhydrogalactitol is in itself chemically
Matter is unstable, ethylene oxide segment may be reduced open loop under the high temperature conditions and loses alkylating, so as to cause drugloading rate
Reduce.
2.1.2 high wet test
Dianhydrogalactitol micro-capsule in embodiment is open respectively and is placed in constant humidity closed container, at 25 DEG C respectively at phase
To being placed 10 days under the conditions of humidity 90% ± 5%, sample, detected by foregoing detection project, as a result in 0 day, 5 days, 10 days
It is shown in Table 3.
The dianhydrogalactitol micro-capsule high humidity result of the test table of table 3
As seen from the data in Table 3, comparative example is placed 10 days under the conditions of relative humidity 90% ± 5%, the sample of comparative example
Product outward appearance is changed into slightly yellow, and drugloading rate and envelop rate reduce, while have a small amount of moisture absorption；And outward appearance, the load medicine of the embodiment of the present invention
Without significant change, hygroscopicity is also lower than comparative example for amount, envelop rate, and this is probably that the softgel shell of micro-capsule serves protective effect.Contrast
It is probably microcapsule wall parts against wear that such case, which occurs, in example, loses defencive function, causes capsule core material to be lost in；Second, capsule core material is gone
Unstable chemcial property of water dulcitol itself, chemical change may occur with external substance or be influenceed by external condition, be caused
Ethylene oxide segment is reduced open loop and loses alkylating, so as to cause drugloading rate to reduce.
2.2 Acceleration study
Embodiment 1~3 three batch test sample (double packaging of aluminium foil bag) is placed in 40 ± 2 DEG C, the constant temperature and humidity of RH75% ± 5%
Placed 6 months in case, sample respectively at 0 month, 1 month, 2 months, 3 months, 6 months, enter by stability high spot reviews project
Row detection, the results are shown in Table 4.
The dianhydrogalactitol micro-capsule accelerated test result table of table 4
It was found from the data of table 4, dianhydrogalactitol micro-capsule of the present invention is in accelerated test, outward appearance, drugloading rate and envelop rate base
This is unchanged, and moisture absorption is little.
By influence factor experiment and accelerated test, when microcapsule wall intact unbroken, protection can be played and gone
The effect of water dulcitol.Therefore dianhydrogalactitol is prepared into micro-capsule, is advantageous to improve its stability, provided for novel form exploitation
Experimental basis.
Although above the present invention is made to retouch in detail with general explanation, embodiment and experiment
State, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, are belonged to claimed
Scope.
Claims (4)
- A kind of 1. dianhydrogalactitol micro-capsule, it is characterised in that the dianhydrogalactitol micro-capsule by following parts by weight supplementary material group Into：1.25~100 parts of dianhydrogalactitol, 5~50 parts of polyacrylic resinⅢ, 3~30 parts of diethyl phthalate, castor-oil plant Oily 1.5~35 parts, 0.08~25 part of mannitol.
- 2. dianhydrogalactitol micro-capsule as claimed in claim 1, it is characterised in that the dianhydrogalactitol micro-capsule is by parts by weight Following supplementary material composition：3.75~50 parts of dianhydrogalactitol, 20~35 parts of polyacrylic resinⅢ, phthalic acid two 12~20 parts of ethyl ester, 6~15 parts of castor oil, 4.5~10 parts of mannitol.
- 3. dianhydrogalactitol micro-capsule as claimed in claim 1 or 2, it is characterised in that be prepared by following methods：1）Take polyacrylic resinⅢ, diethyl phthalate to be dissolved in acetone and capsule material solution is made；2）Take dianhydrogalactitol to be dissolved in ethanol, add step 1）In gained capsule material solution, castor oil and mannitol are added, Fully it is spray-dried, is produced after dissolving.
- 4. dianhydrogalactitol micro-capsule as claimed in claim 3, it is characterised in that step 2）The ethanol is that percent by volume is dense Ethanol of the degree not less than 90%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681483A (en) * | 2002-07-26 | 2005-10-12 | 弗拉梅技术公司 | Improved oral microcapsule with low-solubility active component |
| CN101160118A (en) * | 2005-02-24 | 2008-04-09 | 依兰药物国际有限公司 | Nanoparticulate formulations of docetaxel and analogues thereof |
| CN101623292A (en) * | 2009-02-27 | 2010-01-13 | 无锡鼎福药业有限公司 | Multi-unit bowel dissolvable preparation of compound alendronate sodium and vitamin D3 and preparation method thereof |
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| WO2009117401A2 (en) * | 2008-03-21 | 2009-09-24 | Elan Pharama International Limited | Compositions for site-specific delivery of imatinib and methods of use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681483A (en) * | 2002-07-26 | 2005-10-12 | 弗拉梅技术公司 | Improved oral microcapsule with low-solubility active component |
| CN101160118A (en) * | 2005-02-24 | 2008-04-09 | 依兰药物国际有限公司 | Nanoparticulate formulations of docetaxel and analogues thereof |
| CN101623292A (en) * | 2009-02-27 | 2010-01-13 | 无锡鼎福药业有限公司 | Multi-unit bowel dissolvable preparation of compound alendronate sodium and vitamin D3 and preparation method thereof |
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