CN107773535A - A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons - Google Patents
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons Download PDFInfo
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- CN107773535A CN107773535A CN201610680058.4A CN201610680058A CN107773535A CN 107773535 A CN107773535 A CN 107773535A CN 201610680058 A CN201610680058 A CN 201610680058A CN 107773535 A CN107773535 A CN 107773535A
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- gefitinib
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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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
- A61K9/14—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
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Abstract
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons：Organic solvent is dissolved in as dispersed phase after Gefitinib and PLGA are mixed（Oil phase（O））, lauryl sodium sulfate aqueous solution is continuous phase（Aqueous phase（W））, by dispersed phase under magnetic agitation（Oil phase（O））It is slowly injected into continuous phase（Aqueous phase（W））In, form oil-in-water（O/W）Type emulsion, continue to stir 3h, after organic solvent is fully volatilized, centrifuge Gefitinib PLGA microballoons, and with after distillation water washing 3 times, be drying to obtain Gefitinib PLGA microballoons.This method is used for the preparation of Gefitinib PLGA microballoons.Beneficial effects of the present invention：There is higher envelop rate under conditions of Gefitinib stability is ensured, can be with drug concentration optimal in keeping body, and extend the pharmaceutically-active time.
Description
Technical field
The present invention relates to medical manufacturing technology field, the Lung targeting of more particularly to a kind of slow releasing carrier of medication or slow release formulation
The preparation method of medicine Gefitinib PLGA microballoons.
Background technology
The target therapeutic agent that Gefitinib on July 1st, 2009 lists in Europe acquisition EMEA official approvals, 2011 2
Month, the Gefitinib piece of Astrazeneca AB's production：Food and medicine Surveillance Authority of the People's Republic of China (PRC) is obtained formally to criticize
Standard, there is the Locally Advanced or transfer non-small cell lung of sensitizing mutation suitable for epidermal growth factor recipient tyrosine kinase gene
The first-line treatment of cancer patient, or for previously receiving the Locally Advanced of chemotherapy or the trouble of Metastatic Nsclc
The treatment of person.
Poly(D,L-lactide-co-glycolide is polymerized at random by two kinds of monomer-lactic acid and hydroxyacetic acid, is a kind of tool
There is the macromolecular organic compound of degradable function, the property with good biocompatibility, nontoxic, good encystation and film forming
Can, it is widely used in pharmacy, medical engineering material and modernization industry field.Different monomer ratios can prepare difference
The PLGA of type, such as：PLGA75:25 represent that the polymer is made up of 75% lactic acid and 25% hydroxyacetic acid；Different lactic acid and
The ratio of hydroxyacetic acid, PLGA mechanical strength and degradability can be influenceed.
Microballoon（microsphere）It is a kind of new delivery system risen the 1970s, it is using suitable
Natural either synthesis high polymer material by carrier wrap up or Drug absorbability and formed spherical or spherical micro-
Grain.It is generally acknowledged that the particle size range of microballoon is at 1 ~ 1000 μm.The major advantage of microball preparation：（1）Solves oral hydrolysis medicine
Method of administration.（2）Select suitable carrier material and optimize preparation technology, medicine can be achieved, and a few weeks or months are slow in vivo
Release, reduction or administration number of times.（3）Target administration is realized, such as microballoon modification, medicine acts on target site.（4）Improve indissoluble
Property medicine solubility and dissolution rate, play slow releasing function.（5）Microballoon is discharged with given pace, to maintain effective blood drug concentration,
Microballoon can contain a variety of medicines, such as chemical classes medicine, protein medicaments, polypeptide, DNA, RNA natural drug, and microballoon
Help medicine can be made to realize the diversification of administering mode, oral, lung, nasal-cavity administration can be passed through.Therefore microballoon is a kind of
Very promising carrier format, it is worth our further research and extension.
The content of the invention
It is an object of the invention to provide a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons.
Above-mentioned purpose is achieved through the following technical solutions：
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons, it is characterised in that preparation process is as follows：
A, Gefitinib and PLGA press 1mg：After 8-16mg ratio mixing, 1-2ml organic solvents are dissolved in as dispersed phase；
B, using percent concentration 0.5%-2% lauryl sodium sulfate aqueous solution 20-60ml as continuous phase；
C, dispersed phase is injected in continuous phase under agitation, forms oil-in-water O/W type emulsions, continue stirring until organic solvent fills
Divide volatilization；
D, the Gefitinib in above-mentioned PLGA oil-in-waters O/W type emulsions is centrifuged, is drying to obtain Gefitinib PLGA microballoons.
On the basis of above-mentioned technical proposal, there is technical scheme further below：
Described PLGA LA and GA molar ratio are 50：50~95：5.
The organic solvent is any of dichloromethane, chloroform, ethyl acetate or acetonitrile.
Dispersed phase and the optimum proportioning of continuous phase are：
A, Gefitinib and PLGA press 1mg：8mg ratio mixing, is dissolved in 1ml organic solvent dichloromethanes as dispersed phase；
B, using the lauryl sodium sulfate aqueous solution 40ml of percent concentration 2% as continuous phase.
Described stirring uses magnetic agitation, and stir speed (S.S.) is 300rpm ~ 15000rpm, and temperature control is at 4 DEG C ~ 40 DEG C.
Beneficial effects of the present invention：
1. ensureing Gefitinib stability using a kind of Lung targeting medicine Gefitinib PLGA microballoons prepared by this method
Under conditions of there is higher envelop rate, can be with drug concentration optimal in keeping body, and extend the pharmaceutically-active time.Cause
This, can be achieved sustained release, the target administration of medicine, have important theory value and actual application prospect.
2. the preparation method has, low simple process, preparation cost, technique favorable reproducibility, sample requirement are few, testing sieve
The prescription and technique of choosing are also scalable to production application, thus have directive significance to the application of industrialization.
Embodiment
Embodiment
Embodiment 1：
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons, it is non-that precision weighs 64mgPLGA and 7.8mg Jis
1.0ml dichloromethane is dissolved in as dispersed phase after being mixed for Buddhist nun（Oil phase）, 2% lauryl sodium sulfate aqueous solution is continuous phase（Water
Phase）40ml, 800rpm be stirred at room temperature it is lower dispersed phase is slowly injected into 40ml continuous phases, formed oil-in-water（O/W）Type emulsion,
Continue to stir 3h, after dichloromethane is fully volatilized, centrifuge Gefitinib PLGA microballoons, and with after distilling water washing 3 times,
It is drying to obtain Gefitinib PLGA microballoons.Gefitinib PLGA microballoons prepared by this method are in ball in electric Microscopic observation result
Shape, size is still uniform, no adhesion.The particle diameter for measuring microballoon is 8 ~ 12 μm, and envelop rate is 85% ~ 90%, and drugloading rate is 9 ~ 15%.Institute
The parts by weight stated unit corresponding with volume parts is mg：ml.
Embodiment 2：
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons, it is non-that precision weighs 80mgPLGA and 7.8mg Jis
1.0ml dichloromethane is dissolved in as dispersed phase after being mixed for Buddhist nun（Oil phase）, 1% lauryl sodium sulfate aqueous solution is continuous phase（Water
Phase）40ml, 800rpm be stirred at room temperature it is lower dispersed phase is slowly injected into 40ml continuous phases, formed oil-in-water（O/W）Type emulsion,
Continue to stir 3h, after dichloromethane is fully volatilized, centrifuge Gefitinib PLGA microballoons, and with after distilling water washing 3 times,
It is drying to obtain Gefitinib PLGA microballoons.Gefitinib PLGA microballoons prepared by this method are in ball in electric Microscopic observation result
Shape, size is still uniform, no adhesion.The particle diameter for measuring microballoon is 8 ~ 12 μm, and envelop rate is 85% ~ 90%, and drugloading rate is 9 ~ 15%.Institute
The parts by weight stated unit corresponding with volume parts is mg：ml.
Embodiment 3：
A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons, it is non-that precision weighs 120mgPLGA and 7.8mg Jis
2.0ml dichloromethane is dissolved in as dispersed phase after being mixed for Buddhist nun（Oil phase）, 0.5% lauryl sodium sulfate aqueous solution is continuous phase
（Aqueous phase）40ml, 800rpm be stirred at room temperature it is lower dispersed phase is slowly injected into 40ml continuous phases, formed oil-in-water（O/W）Type breast
Agent, continue to stir 3h, after dichloromethane is fully volatilized, centrifuge Gefitinib PLGA microballoons, and with distilling water washing 3 times
Afterwards, Gefitinib PLGA microballoons are drying to obtain.Gefitinib PLGA microballoons prepared by this method are in electric Microscopic observation result
Spherical in shape, size is still uniform, no adhesion.Measure microballoon particle diameter be 8 ~ 12 μm, envelop rate be 85% ~ 90%, drugloading rate be 9 ~
15%.Described parts by weight unit corresponding with volume parts is mg：ml.
Claims (5)
1. a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons, it is characterised in that preparation process is as follows：
A, Gefitinib and PLGA press 1mg：After 8-16mg ratio mixing, 1-2ml organic solvents are dissolved in as dispersed phase；
B, using percent concentration 0.5%-2% lauryl sodium sulfate aqueous solution 20-60ml as continuous phase；
C, dispersed phase is injected in continuous phase under agitation, forms oil-in-water O/W type emulsions, continue stirring until organic solvent fills
Divide volatilization；
D, the Gefitinib in above-mentioned PLGA oil-in-waters O/W type emulsions is centrifuged, is drying to obtain Gefitinib PLGA microballoons.
2. a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons according to claim 1, its feature
The molar ratio for being described PLGA LA and GA is 50：50~95：5.
3. a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons according to claim 1, its feature
It is the organic solvent for any of dichloromethane, chloroform, ethyl acetate or acetonitrile.
4. a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons according to claim 1 or 3, it is special
Sign is：
A, Gefitinib and PLGA press 1mg：8mg ratio mixing, is dissolved in 1ml organic solvent dichloromethanes as dispersed phase；
B, using the lauryl sodium sulfate aqueous solution 40ml of percent concentration 2% as continuous phase.
5. a kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons according to claim 4, its feature
It is that described stirring uses magnetic agitation, stir speed (S.S.) is 300rpm ~ 15000rpm, and temperature control is at 4 DEG C ~ 40 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610680058.4A CN107773535A (en) | 2016-08-18 | 2016-08-18 | A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons |
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| CN201610680058.4A CN107773535A (en) | 2016-08-18 | 2016-08-18 | A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons |
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| CN107773535A true CN107773535A (en) | 2018-03-09 |
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| CN201610680058.4A Pending CN107773535A (en) | 2016-08-18 | 2016-08-18 | A kind of preparation method of Lung targeting medicine Gefitinib PLGA microballoons |
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2016
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Application publication date: 20180309 |