CN105581996A - Dianhydrodulcitol microcapsule and preparation method thereof - Google Patents

Dianhydrodulcitol microcapsule and preparation method thereof Download PDF

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Publication number
CN105581996A
CN105581996A CN201610098241.3A CN201610098241A CN105581996A CN 105581996 A CN105581996 A CN 105581996A CN 201610098241 A CN201610098241 A CN 201610098241A CN 105581996 A CN105581996 A CN 105581996A
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capsule
dianhydrogalactitol
micro
parts
dissolved
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CN105581996B (en
Inventor
陈建惠
刘冠萍
郑志远
杨北妮
林艳英
黄源春
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Guangxi Wuzhou Pharmaceutical Group Co Ltd
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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
    • A61K31/33—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

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a dianhydrodulcitol microcapsule and a preparation method thereof. The prescription of the microcapsule preparation mainly comprises dianhydrodulcitol, polyacrylic resin III, diethyl phthalate, castor oil and mannitol. Tests result indicate that the microcapsule is round and regular, has a grain size of 45-100mu m, an encapsulation efficiency of more than or equal to 80 percent and a drug loading capacity of 30.2-35.8 percent, and has a relatively high stability.

Description

A kind of dianhydrogalactitol micro-capsule and preparation method thereof
Technical field
The present invention relates to Medicinal invention field, relate in particular to a kind of prescription composition and system thereof of dianhydrogalactitol micro-capsulePreparation Method.
Background technology
Chronic myelocytic leukemia (ChronicMyelogenousLeukemia, CML) be a kind of affect blood andThe malignant tumour of marrow, its notable feature is granulocytic excessive generation in marrow and peripheral blood. At present except different baseOutside HSCT, there is no radical cure way, Allogeneic Bone Marrow Transplantation is to cure so far CMLTherapy likely, but its success rate is only 33% left and right, and expense is up to hundreds thousand of, and patient is conventionally unable negativeLoad. Therefore, main treatment means clinically, are still after radiotherapy or chemotherapy, are treated and are made patient by medicineThe state of an illness obtains to be alleviated.
Dianhydrogalactitol (chemistry 1,2,5,6-NSC-132313 by name) is the bis-epoxy of mitolactol hydrogen bromideCompound, is white column, flaky crystal or crystalline powder, odorless, micro-hardship, soluble in water, ethanol,In acetone, ethyl acetate, dissolve; It is hexasaccharide cancer therapy drug, has cross resistance, also with alkylating agent simultaneouslyCan be classified as alkylating agent class, but its mechanism of action can not be explained with this completely. Known through By consulting literatures, anhydrate and defendLance alcohol (DAG) can be combined by the GGCC sequence on DNA, inducing DNA fracture, thus produceRaw antitumor action; It is synthetic that DAG can suppress the large biological molecule such as nucleic acid and albumen, and animal transplanting tumor is hadThe antitumor action of wide spectrum; Show through clinical trial, DAG has near preferably to chronic myelocytic leukemia simultaneouslyPhase curative effect, remission rate reaches 86%, and effective very fast, and drug combination can produce synergy, and can pass through blood brainBarrier, non-stimulated to blood vessel, to the harmless effect of hepatic and renal function. This is some other common cancer therapy drug instituteCan not compare. Dianhydrogalactitol structural formula is as follows:
At present dianhydrogalactitol belongs to intravenous injection, and compliance is low, if liquid exosmoses when injection, may cause officePortion's necrosis, forms ulcer, should prevent that liquid from exosmosing when use; It is simultaneously known by analyzing its chemical formula,Dianhydrogalactitol is extremely unstable, and oxirane is easily reduced open loop and loses alkylating, thus activity decreased.Therefore need to find at present a kind of method that can improve dianhydrogalactitol compliance and stability.
Summary of the invention
The object of this invention is to provide a kind of dianhydrogalactitol micro-capsule.
Another object of the present invention is to provide a kind of preparation method of dianhydrogalactitol micro-capsule.
Because existing dianhydrogalactitol is injecting drug use, exist medication inconvenience, liquid to exosmose and form ulcer etc.Problem, therefore, need to provide a kind of product that is convenient for carrying and uses, and increases medicine-feeding way, and adapting to market needsAsk. Show through experimental study, dianhydrogalactitol is made after micro-capsule, not only improved its stability, Er QiegongSkill is stable, and cost is low, can be made into multiple oral formulations, and convenient drug administration has improved patient's compliance preferably.
Inventor finds under study for action, dianhydrogalactitol micro-capsule use common capsule material as gelatin, Arabic gum,When the material such as shitosan, alginate, because above material all dissolves in stomach, discharge the winged euonymus that anhydratesAlcohol, dianhydrogalactitol oxirane under gastrointestinal enzyme system is very easily reduced open loop and loses alkylating, therebyLose activity. The interior environment of digesting and assimilating in the medicinal property in conjunction with dianhydrogalactitol, human body and the property of capsule materialMatter, after repetition test, has finally selected the polyacrylic resinⅢ of enteric solubility and mixing of diethyl phthalateCompound is as the capsule material of the lance alcohol that anhydrates. Polyacrylic resinⅢ and diethyl phthalate be a kind of to pHFor responsive poly-compounds, our experiments show that, polyacrylic resinⅢ and diethyl phthalate are at pHWhen > 7, just dissolve, can in alimentary canal, discharge medicine by privileged site as capsule material, reducing gastrointestinal enzyme is to medicineThe metabolism of thing, is conducive to improve the bioavilability of medicine.
While preparing dianhydrogalactitol micro-capsule, if without plasticizer, finished product cyst wall partial crushing, parcel is not exclusively; LogicalCross the elongation degree ε while measuring fractureR(%) judge the compliance of film, our experiments show that fat-soluble plasticizer castorThe ε of sesame oilR> 81%, water-soluble plasticizer is as the ε of glycerine, PEGRBe worth within the scope of 34%-53%, forThe stabilising membrane not breaking while obtaining normal operating and storage, is convenient to be developed to more multi-form, therefore screens castor oilFor plasticizer. In experimentation, find, if nonreactive is adhered agent, part micro-capsule is adhered conglomeration, with tristearin simultaneouslyThe antiblocking agent raw materials such as acid magnesium, talcum powder, single stearic acid glycerine lipoprotein, 18 alcohol, sweet mellow wine are tested through many experimentsAfter card, find that sweet mellow wine not only can overcome the phenomenon that is adhered of micro-capsule, and can improve envelop rate, therefore choosingBe adhered agent as anti-with sweet mellow wine.
The present invention realizes by following technical scheme:
The preparation prescription of dianhydrogalactitol microcapsules of the present invention, is made up of the supplementary material of following weight portion: 1.25～100 parts of dianhydrogalactitols, 5～50 parts of polyacrylic resinⅢs, diethyl phthalate 3～30 parts, 1.5～3.5 parts of castor oil, 0.08～2.5 part, sweet mellow wine.
Preferably, formed by the supplementary material of following weight portion: 3.75～50 parts of dianhydrogalactitols, polyacrylic acid20～35 parts of resin IIIs, 12～20 parts of diethyl phthalates, 6～15 parts of castor oil, sweet mellow wine 4.5～10 parts.
Spray drying technology has become the effective ways of medicament microcapsule at present, have easy and simple to handle, controllability good,The features such as encystation rate is high, product dispersion are the microencapsulation methods that tool industrial applications is worth. At selective solventTime, to analyze from dianhydrogalactitol chemical property, it is soluble in water, ethanol, methyl alcohol, acetone, acetic acid secondIn ester, but because water is difficult to volatilization in the time that spraying is dry, the micro-capsule of formation is adhered agglomerating; Methyl alcohol, ethyl acetateThere is certain toxicity, in spraying is dry, often occur dissolvent residual. Through experimental verification in many ways, select concentrationBe that more than 90% ethanol and acetone are as solvent.
Dianhydrogalactitol micro-capsule of the present invention is prepared from by following steps:
1) getting polyacrylic resinⅢ, diethyl phthalate is dissolved in and in acetone, makes capsule material solution;
2) get dianhydrogalactitol and be dissolved in ethanol, add step 1) in gained capsule material solution, then add castor-oil plantOil and sweet mellow wine, spray after fully dissolving dry, to obtain final product.
Preferably, described ethanol, concentration of volume percent is not less than 90%.
Dianhydrogalactitol microcapsules provided by the invention has the following advantages:
1, the present invention adopts spray drying process that dianhydrogalactitol is made to micro-capsule, have easy and simple to handle, controllability good,The features such as encystation rate is high, product dispersion are the microencapsulation methods that tool industrial applications is worth.
2, the present invention makes dianhydrogalactitol after micro-capsule, has not only improved its stability, and process stabilizing,Cost is low, can be made into several formulations, and convenient drug administration has improved patient's compliance preferably.
3, dianhydrogalactitol micro-capsule of the present invention can dissolve by privileged site in intestines, discharges medicine, is conducive to improveThe bioavilability of dianhydrogalactitol.
Detailed description of the invention
Following examples are used for illustrating the present invention, but are not used for limiting the scope of the invention. Wherein plasticizer is with anti-Being adhered agent consumption is to obtain taking capsule material use quantity as benchmark, and the concentration that the present invention indicates is weight volumetric concentration.
Embodiment 1:
Taking 5kg polyacrylic resinⅢ and 3kg diethyl phthalate is dissolved in 1000L acetone and makesCapsule material solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, addsEnter 1.5kg castor oil, the sweet mellow wine of 0.8kg, sprays after fully dissolving dry.
Embodiment 2:
Taking 50kg polyacrylic resinⅢ and 30kg diethyl phthalate is dissolved in 1000L acetone and makesObtain capsule material solution, take dianhydrogalactitol 100kg and be dissolved in a small amount of ethanol, join in capsule material solution, addEnter 35kg castor oil, the sweet mellow wine of 25kg, sprays after fully dissolving dry.
Embodiment 3:
Taking 20kg polyacrylic resinⅢ and 12kg diethyl phthalate is dissolved in 1000L acetone and makesObtain capsule material solution, take dianhydrogalactitol 3.75kg and be dissolved in a small amount of ethanol, join in capsule material solution, addEnter 6kg castor oil, the sweet mellow wine of 4.5kg, sprays after fully dissolving dry.
Embodiment 4:
Taking 35kg polyacrylic resinⅢ and 20kg diethyl phthalate is dissolved in 1000L acetone and makesObtain capsule material solution, take dianhydrogalactitol 50kg and be dissolved in a small amount of ethanol, join in capsule material solution, addEnter 15kg castor oil, the sweet mellow wine of 10kg, sprays after fully dissolving dry.
Embodiment 5:
Taking 25kg polyacrylic resinⅢ and 17kg diethyl phthalate is dissolved in 1000L acetone and makesObtain capsule material solution, take dianhydrogalactitol 10kg and be dissolved in a small amount of ethanol, join in capsule material solution, addEnter 5kg castor oil, the sweet mellow wine of 2kg, sprays after fully dissolving dry.
Embodiment 6:
Get the micro-capsule of gained in embodiment 1～5, the encapsulated dianhydrogalactitol capsule that obtains.
Embodiment 7:
Get the micro-capsule of gained in embodiment 1～5, suppress by normal compressing tablet operation, obtain dianhydrogalactitolTablet.
Comparative example 1:
Taking 4kg polyacrylic resinⅢ and 3kg diethyl phthalate is dissolved in 1000L acetone and makesCapsule material solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, addsEnter 1.5kg castor oil, the sweet mellow wine of 0.8kg, sprays after fully dissolving dry.
Comparative example 2:
Taking 55kg polyacrylic resinⅢ and 3kg diethyl phthalate is dissolved in 1000L acetone and makesCapsule material solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, addsEnter 1.5kg castor oil, the sweet mellow wine of 0.8kg, sprays after fully dissolving dry.
Comparative example 3:
Taking 5kg polyacrylic resinⅢ and 3kg diethyl phthalate is dissolved in 1000L acetone and makesCapsule material solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, addsEnter 1kg castor oil, the sweet mellow wine of 0.5kg, sprays after fully dissolving dry.
Comparative example 4:
Taking 5kg polyacrylic resinⅢ and 3kg diethyl phthalate is dissolved in 1000L acetone and makesCapsule material solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, addsEnter 37kg castor oil, the sweet mellow wine of 26kg, sprays after fully dissolving dry.
Comparative example 5:
Take 10kg HP55 and be dissolved in 1000L acetone and make capsule material solution, take and anhydrateDulcitol 1.25kg is dissolved in a small amount of ethanol, joins in capsule material solution, adds 1.5kg castor oil, 0.8kgSweet mellow wine, after fully dissolving, spray and is dried.
Comparative example 6:
Taking 5kg polyacrylic resinⅢ and 31kg diethyl phthalate is dissolved in 1000L acetone and makes capsuleMaterial solution, takes dianhydrogalactitol 1.25kg and is dissolved in a small amount of ethanol, joins in capsule material solution, adds 1.5kgCastor oil, the sweet mellow wine of 0.8kg, sprays after fully dissolving dry.
Quality evaluation experiment:
1, the mensuration of the form of micro-capsule, particle diameter, envelop rate and medicine carrying amount
The assay method of 1.1 envelop rates and medicine carrying amount:
Actual content of dispersion in envelop rate (%)=micro-capsule/reality dispensing total amount × 100%;
Actual content of dispersion/micro-capsule gross weight × 100% in medicine carrying amount (%)=micro-capsule.
1.2 forms and particle size determination method: adopt SEM (SME) to observe the surperficial shape of micro-capsuleState, measures its particle diameter with Zetasizer laser particle size analyzer.
1.3 content assaying method
The preparation of solution: get dianhydrogalactitol reference substance appropriate, accurately weighed, add Methanol into about 100 μ g/mLReference substance solution. Get the about 0.1g of dianhydrogalactitol micro-capsule, accurately weighed, in 100mL measuring bottle, add firstThe appropriate ultrasonic 1h of alcohol dissolves it, puts to room temperature, adds methanol constant volume to scale, shakes up, and filters, and gets continuous filterLiquid is as need testing solution: prepare negative control solution with blank micro-capsule by the preparation method of need testing solution.
Chromatographic condition:
Chromatographic column: AgilentDB-1 (30m × 0.53mm, 1.5 μ are m);
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, and flow velocity is 5ml/min; Split ratio: 1:10; Sampling volume is 1 μ l.
Number of theoretical plate calculates and is not less than 20000, the separating degree between dianhydrogalactitol and each impurity by dianhydrogalactitol peakAll should conform with the regulations.
1.4 measurement results are in table 1.
Table 1 dianhydrogalactitol micro-capsule form, particle diameter, entrapment efficiency determination result table
The mode of appearance of dianhydrogalactitol micro-capsule, envelop rate and medicine carrying amount when table 1 result shows different proportioning, realExecute the preparation prescription of routine 1-5 and can prepare mode of appearance rounding, envelop rate higher (all > 90%), medicine carryingAmount is good. Can see from the testing result of comparative example 1,3, when the consumption of each auxiliary material component is lower than of the present inventionWhen prescription scope, there is change in the form of micro-capsule, most surface fractures, and envelop rate and medicine carrying amount reduce. WithTime can see from comparative example 2,5, and in the time that the content of capsule material is greater than claimed range of the present invention, the particle diameter of micro-capsule is brightAobvious change greatly, and there is the situation that part micropill is adhered. From comparative example 4, can see, when castor oil and sweet dewThe content of alcohol is during higher than scope of the presently claimed invention, micro-capsule surface due to plasticising and anti-glutinous effect too strong, causeMost surfaces is coarse uneven. Can see by comparative example 5, when the capsule material in micro-capsule of the present invention simultaneouslyWhen polyacrylic resinⅢ and diethyl phthalate are transformed into polyacrylic resinⅢ, micro-capsule any surface finish,Be not adhered, envelop rate and medicine carrying amount all meet pharmacopeia requirement, do not meet pharmacopeia requirement but particle diameter is excessive. Simultaneously logicalOverscanning electron microscope (SME) is observed the configuration of surface of micro-capsule and is used Zetasizer laser particle size analyzerMeasure its particle diameter, result shows the equal form rounding of the dianhydrogalactitol micro-capsule in embodiment, and particle diameter is mainly distributed inBetween 45-100 μ m. Comprehensive above experimental result analysis obtain, dianhydrogalactitol microcapsules of the present inventionPreparation prescription composition should be: 1.25～100 parts of dianhydrogalactitols, 5～50 parts of polyacrylic resinⅢs, neighbour3～30 parts of diethyl phthalates, castor oil 1.5-3.5 part, sweet mellow wine 0.08-2.5 part. Wherein optimum prescriptionFor: 3.75～50 parts of dianhydrogalactitols, 20～35 parts of polyacrylic resinⅢs, diethyl phthalate 12～20 parts, castor oil 6-15 part, sweet mellow wine 4.5-10 part.
2, dianhydrogalactitol micro-capsule stability test
2.1 influence factor tests
Influence factor test is the stability of preparation to be detected under the more violent condition of experiment than accelerating,This test, mainly taking comparative example 1,2,4 as control group, is got embodiment 1-3 simultaneously and is carried out influence factor experiment, logicalCross observation outward appearance, detect weightening finish, medicine carrying amount and envelop rate and investigate its stability.
2.1.1 hot test
By dianhydrogalactitol micro-capsule in embodiment respectively opening be placed in suitable clean container, in 60 DEG C of insulating boxsUnder, place 10 days, in sampling in 0 day, 5 days, 10 days, detect by aforementioned test item, the results are shown in Table 2.
Table 2 dianhydrogalactitol micro-capsule hot test result
As seen from the data in Table 2, sample is placed 10 days under 60 DEG C of conditions, and the sample appearance of comparative example becomes micro-yellow,Medicine carrying amount and envelop rate reduce; And the outward appearance of embodiment, medicine carrying amount, envelop rate are without significant change. Comparative example goes outExisting this situation may be the breakage of micro-capsule cyst wall part, under hot conditions, loses defencive function, the 2nd, and capsule core materialThe unstable chemcial property of dianhydrogalactitol own, may be reduced open loop at ethylene oxide segment under hot conditions and loseAlkylation removal effect, thus cause medicine carrying amount to reduce.
2.1.2 high wet test
By the dianhydrogalactitol micro-capsule in embodiment respectively opening be placed in constant humidity closed container, 25 DEG C of differenceUnder relative humidity 90% ± 5% condition, place 10 days, in sampling in 0 day, 5 days, 10 days, enter by aforementioned test itemRow detects, and the results are shown in Table 3.
Table 3 dianhydrogalactitol micro-capsule high humidity result of the test table
As seen from the data in Table 3, comparative example is placed 10 days under relative humidity 90% ± 5% condition, comparative exampleSample appearance becomes micro-yellow, and medicine carrying amount and envelop rate reduce, and have a small amount of moisture absorption simultaneously; And the embodiment of the present inventionOutward appearance, medicine carrying amount, envelop rate without significant change, hygroscopicity is also low than comparative example, this may be the capsule of micro-capsuleShell has played protective effect. Comparative example occurs that this situation may be the breakage of micro-capsule cyst wall part, loses protection meritCan, cause capsule core material to run off; The 2nd, the unstable chemcial property of capsule core material dianhydrogalactitol own, may with the external worldMaterial generation chemical change or affected by external condition, causes ethylene oxide segment to be reduced open loop and loses alkylTurn use into, thereby cause medicine carrying amount to reduce.
2.2 accelerate experiment
Embodiment 1～3 three batch test sample (two packaging of aluminium foil bag) is placed in to 40 ± 2 DEG C, the constant temperature of RH75% ± 5%In constant humidity cabinet, place 6 months, respectively at sampling in 0 month, 1 month, 2 months, 3 months, 6 months, by stableProperty high spot reviews project detects, and the results are shown in Table 4.
Table 4 dianhydrogalactitol micro-capsule accelerated test result table
From table 4 data, dianhydrogalactitol micro-capsule of the present invention in accelerated test, outward appearance, medicine carrying amount and sealRate is substantially unchanged, and moisture absorption is very micro-.
By influence factor test and accelerated test known, when micro-capsule cyst wall is complete when damaged, can play guarantorProtect the effect of dianhydrogalactitol. Therefore dianhydrogalactitol is prepared into micro-capsule, is conducive to improve its stability, forNovel form exploitation provides experimental basis.
Although, above use general explanation, detailed description of the invention and test, the present invention is done detailedDescription, but on basis of the present invention, can make some modifications or improvements it, this is to those skilled in the artApparent. Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention,All belong to the scope of protection of present invention.

Claims (4)

1. a dianhydrogalactitol micro-capsule, it is characterized in that, described dianhydrogalactitol micro-capsule is made up of the supplementary material of following weight portion: 1.25～100 parts of dianhydrogalactitols, 5～50 parts of polyacrylic resinⅢs, 3～30 parts of diethyl phthalates, 1.5～35 parts of castor oil, 0.08～25 part, sweet mellow wine.
2. dianhydrogalactitol micro-capsule as claimed in claim 1, it is characterized in that, described dianhydrogalactitol micro-capsule is made up of the following supplementary material of weight portion: 3.75～50 parts of dianhydrogalactitols, 20～35 parts of polyacrylic resinⅢs, 12～20 parts of diethyl phthalates, 6～15 parts of castor oil, 4.5～10 parts, sweet mellow wine.
3. dianhydrogalactitol micro-capsule as claimed in claim 1 or 2, is characterized in that being prepared from by following methods:
1) getting polyacrylic resinⅢ, diethyl phthalate is dissolved in and in acetone, makes capsule material solution;
2) get dianhydrogalactitol and be dissolved in ethanol, add in step 1) gained capsule material solution, then add castor oil and sweet mellow wine, after fully dissolving, spray dry, to obtain final product.
4. dianhydrogalactitol micro-capsule as claimed in claim 3, is characterized in that step 2) described ethanol is that concentration of volume percent is not less than 90% ethanol.
CN201610098241.3A 2016-02-23 2016-02-23 A kind of dianhydrogalactitol micro-capsule and preparation method thereof Active CN105581996B (en)

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Citations (4)

* Cited by examiner, † Cited by third party
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
WO2009117401A2 (en) * 2008-03-21 2009-09-24 Elan Pharama International Limited Compositions for site-specific delivery of imatinib and methods of use
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

Patent Citations (4)

* Cited by examiner, † Cited by third party
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
WO2009117401A2 (en) * 2008-03-21 2009-09-24 Elan Pharama International Limited Compositions for site-specific delivery of imatinib and methods of use
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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