CN106309383A - Drug microcarrier based on egg white and preparation method thereof - Google Patents
Drug microcarrier based on egg white and preparation method thereof Download PDFInfo
- Publication number
- CN106309383A CN106309383A CN201610978809.0A CN201610978809A CN106309383A CN 106309383 A CN106309383 A CN 106309383A CN 201610978809 A CN201610978809 A CN 201610978809A CN 106309383 A CN106309383 A CN 106309383A
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- Prior art keywords
- gallus domesticus
- ovum gallus
- domesticus album
- medicine
- microcarrier
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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
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- Epidemiology (AREA)
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- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Abstract
The invention discloses a drug microcarrier based on egg white and a preparation method thereof. The preparation method is characterized by comprising the following steps: emulsifying a drug-containing egg white solution through a microfluidic device to obtain an egg white droplet template, and solidifying the template through a chemical or physical method. After being solidified, the egg white can be degraded by in-vivo proteinase to realize slow release of the drug, thus proving that the egg white is an ideal material for preparing the drug microcarrier. According to the invention, the preparation method is simple to operate, low in cost and convenient to realize large-scale production; and the prepared drug microcarrier is non-toxic, and has excellent biocompatibility, biofunctionability and biodegradability.
Description
Technical field
The invention belongs to biological medicine investigation of materials technical field, be specifically related to a kind of Ovum Gallus domesticus album medicine microcarrier and preparation thereof
Method.
Background technology
Along with science and technology growing, the development of pharmaceutics has been enter into brand-new epoch, all kinds of newtype drugs
Dosage form develops towards storage-stable, nanoparticle, controlled release fertilizer direction, in order to better controls over dose, increase operation rate
With reduction toxic and side effects, can effectively treat disease and can alleviate again sufferer misery, reduce toxic and side effects.Therefore, medicament slow release is received
Rice microball preparation becomes the key content of medicine novel form research.The material being currently used for preparing medicine microcarrier mainly includes gathering
Esters and copolymer (such as poly lactic coglycolic acid), poe, poly-phospholipid, polylactic acid and the Sargassum of other materials
Acid sodium etc..As the material of slow releasing carrier of medication, it is the important component part in drug controlled release system, is that regulating drug is released
Put the important substance of speed, be also the principal element affecting drug effectiveness.Slow releasing carrier of medication material needs to have excellent
Biocompatibility and biodegradability, should be able to degradation in vivo be also micromolecular compound with regard to this material, thus by body
Metabolism, absorbing or drain, to human non-toxic's side effect, and the time of origin of degradation process should be suitable.At medicament sustained-release nano
In the research of microball preparation, selecting suitable drug carrier material is one of the most key element task, is related to medicine and delays
Can the development work that release system be smoothed out, and the using effect of relation medicine.But great majority to be used for preparing medicine micro-
The material cost of carrier is high, and preparation method complexity is loaded down with trivial details, and is presented with to be hoisted in terms of biocompatibility and degradability,
So limiting the application in clinic of the medicine microcarrier.
Birds and birds Ovum Gallus domesticus album, as a kind of natural protein source, the most just receive food industry and medical treatment
The extensive concern in field, such as, utilize Ovum Gallus domesticus album to carry out repair in trauma and vaccine manufacture etc., thus the biocompatibility of Ovum Gallus domesticus album and merit
Property can have been widely recognized already and pay close attention to.As a example by Ovum Gallus domesticus album, protein contained in Ovum Gallus domesticus album can belong to difference
A few proteinoid families, including an enzyme level albumen, transferrins, Kazal type protease inhibitor, glycosyl hydrolase, fat
Matter transporter, antibacterial anatonosis albumen, clusterin, cystatin, VMO-1 albumen and uPAR/CD59/
Ly6/ snake venom neurotoxin folic acid receptor.Protein main in Ovum Gallus domesticus album includes: ovalbumin, ovotransferrin/companion are clearly
Albumen, ovomucoid and ovomucin；Other protein include: the solid egg of lysozyme, ovoinhibitor, ovomacroglobulin/ovum
In vain, cystatin and Avidin.Meanwhile, though birds Ovum Gallus domesticus album can not be degraded automatically, but owing to Ovum Gallus domesticus album can regard a kind of broad sense as
Protein, enter, at it, the protease hydrolysis can being correlated with after human body, be finally absorbed by the body, so also referred to as " can drop
Solve " material.Ovum Gallus domesticus album has excellent biocompatibility, Biofunctional and its characteristic nontoxic, degradable, so Ovum Gallus domesticus album is
A kind of ideal material preparing medicine microcarrier, meanwhile, it is in other biological medical material and Three-dimensional cell culture field also
Have broad application prospects.
Summary of the invention
Present invention aim at providing a kind of medicine microcarrier based on Ovum Gallus domesticus album and preparation method thereof, its preparation process letter
Single, size is controlled, and monodispersity and repeatability are good, have good biocompatibility, functional and biodegradable simultaneously
Property.
In order to solve these problems of the prior art, present invention provide the technical scheme that
It is characterized in that described Ovum Gallus domesticus album medicine microcarrier first passes through the egg white solution acquisition that micro fluidic device emulsifying contains medicine
Ovum Gallus domesticus album drop template, template solidification is obtained by the chemically or physically method that recycles.Microsphere enter after human body can by protease hydrolysis,
Thus meet for drug controlled release system and the requirement of medicine microcarrier degradability.
Another object of the present invention is to provide a kind of medicine microcarrier based on Ovum Gallus domesticus album and preparation method thereof, its feature exists
In said method comprising the steps of:
(1) extraction of Ovum Gallus domesticus album:
Selected eggs surface is thoroughly cleaned, with egg device, Ovum Gallus domesticus album is separated with egg yolk, the Ovum Gallus domesticus album of isolated is carried out
Filter, take the Ovum Gallus domesticus album weak solution leached standby；
(2) preparation of the Ovum Gallus domesticus album emulsion containing medicine:
Micro fluidic device and the Ovum Gallus domesticus album weak solution containing medicine is utilized to prepare size tunable, uniform Ovum Gallus domesticus album emulsion, Janus
Ovum Gallus domesticus album emulsion or multicomponent (more than three components or three components) Ovum Gallus domesticus album emulsion；
(3) solidification of the Ovum Gallus domesticus album emulsion containing medicine:
By chemically or physically method, the Ovum Gallus domesticus album emulsion containing medicine is solidified, after cleaning, i.e. can get the micro-load of Ovum Gallus domesticus album medicine
Body；
(4) degraded of Ovum Gallus domesticus album medicine microcarrier:
Ovum Gallus domesticus album medicine microcarrier is placed in certain density enzymatic solution, growth over time, medicine microcarrier be can be observed
Fluorescence gradually weaken, i.e. microcarrier is degraded by enzymes it is achieved thereby that medicament slow release.
Preferably, the Ovum Gallus domesticus album described in step (1) is retrieved from chicken, duck, goose, the various birds of Carnis Coturnicis japonicae or the egg ovum of birds.
Preferably, the Ovum Gallus domesticus album emulsion size containing medicine prepared by microflow control technique described in step (2) is 5 μm-500
μm。
Preferably, medicine described in step (2) be doxorubicin hydrochloride, hydrochloric acid hycamtin, gemcitabine hydrochloride, carboplatin,
One or more in cytarabine hydrochloride, mustine hydrochlcride, mitoxantrone hydrochloride, aspirin, water soluble vitamins
Combination in any.
Preferably, the curing of the Ovum Gallus domesticus album emulsion described in step (3) is heating, ultra-vioket radiation, strong acid-base, ethanol change
Property.
Preferably, the enzyme causing medicine microcarrier to be degraded described in step (4) can be in protease one or both with
On combination in any.
A kind of medicine microcarrier based on Ovum Gallus domesticus album of the present invention and preparation method thereof includes the extraction of early stage Ovum Gallus domesticus album, utilizes and extracts
Ovum Gallus domesticus album weak solution hybrid medicine carry out the preparation of emulsion, after collection, the emulsion containing medicine solidified and clean,
Obtain Ovum Gallus domesticus album medicine microcarrier.By internal proteasome degradation, thus medicament slow release can be realized after Ovum Gallus domesticus album solidification, so this micro-load
Body can meet the requirement of medicine microcarrier.Said method comprising the steps of:
(1) extraction of Ovum Gallus domesticus album:
Selected eggs surface is thoroughly cleaned, with egg device, Ovum Gallus domesticus album is separated with egg yolk, the Ovum Gallus domesticus album of isolated is carried out
Filter, take the Ovum Gallus domesticus album weak solution leached standby；
(2) preparation of the Ovum Gallus domesticus album emulsion containing medicine:
Micro fluidic device and the Ovum Gallus domesticus album weak solution containing medicine is utilized to prepare size tunable, uniform Ovum Gallus domesticus album emulsion, Janus
Ovum Gallus domesticus album emulsion or multicomponent (more than three components or three components) Ovum Gallus domesticus album emulsion；
(3) solidification of the Ovum Gallus domesticus album emulsion containing medicine:
By chemically or physically method, the Ovum Gallus domesticus album emulsion containing medicine is solidified, after cleaning, i.e. can get the micro-load of Ovum Gallus domesticus album medicine
Body；
(4) degraded of Ovum Gallus domesticus album medicine microcarrier:
Ovum Gallus domesticus album medicine microcarrier is placed in certain density enzymatic solution, growth over time, medicine microcarrier be can be observed
Fluorescence gradually weaken, i.e. microcarrier is degraded by enzymes it is achieved thereby that medicament slow release.
Relative to scheme of the prior art, the invention have the advantage that
A kind of medicine microcarrier based on Ovum Gallus domesticus album of the present invention, microsphere is mainly composed of birds or birds Ovum Gallus domesticus album, and Ovum Gallus domesticus album is nontoxic, and tool
There is good biocompatibility and functional, simultaneously because Ovum Gallus domesticus album can be considered a kind of broad sense protein, can be by egg after entering human body
White enzyme hydrolysis, is finally absorbed by the body, so degradation material can be regarded as, it is possible to realize medicament slow release, therefore, Ovum Gallus domesticus album is
A kind of ideal material preparing medicine microcarrier, Ovum Gallus domesticus album also has at other biological medical material and Three-dimensional cell culture field simultaneously
Broad prospect of application.
Ovum Gallus domesticus album medicine microcarrier of the present invention, as one list emulsion microsphere, Janus microsphere or multicomponent microsphere, has preparation
Method is simple, material is easy to get, with low cost, be prone to the features such as large-scale production, beneficially Ovum Gallus domesticus album medicine microcarrier is in clinic
Application.
Accompanying drawing explanation
Below in conjunction with the accompanying drawings and embodiment the invention will be further described:
Fig. 1 is the schematic diagram utilizing the single emulsion Ovum Gallus domesticus album medicine microcarrier of micro fluidic device preparation；
Fig. 2 is schematic diagram (the multicomponent Ovum Gallus domesticus album medicine microcarrier utilizing micro fluidic device to prepare Janus Ovum Gallus domesticus album medicine microcarrier
Preparation process is similar with Janus microcarrier)；
Fig. 3 is for increase over time, and the instance graph that medicine (doxorubicin hydrochloride) microcarrier fluorescence gradually weakens, scale is 150
μm (is followed successively by degraded 3h, 4h, 5h fluorescing matter) from left to right.
Detailed description of the invention
Below in conjunction with specific embodiment, such scheme is described further.Should be understood that these embodiments are for illustrating
The present invention and be not limited to limit the scope of the present invention.The implementation condition used in embodiment can be done according to the condition of concrete producer
Adjusting further, not marked implementation condition is usually the condition in normal experiment.
Embodiment 1 one kinds medicine based on Ovum Gallus domesticus album microcarrier preparation method
1. the extraction of Ovum Gallus domesticus album: thoroughly clean Fresh Egg surface with 70% ethanol, afterwards with egg device by Ovum Gallus domesticus album
Separate with egg yolk, isolated Ovum Gallus domesticus album gauze is filtered, take the Ovum Gallus domesticus album weak solution leached standby.
2. contain the preparation of the Ovum Gallus domesticus album emulsion of doxorubicin hydrochloride: the micro fluidic device material preparing Ovum Gallus domesticus album microsphere is
Borosilicate, internal phase i.e. discontinuous phase material is to be mixed with the Ovum Gallus domesticus album weak solution that concentration is 1mg/mL doxorubicin hydrochloride, foreign minister
I.e. continuous state material is leaching type soybean oil.(foreign minister flows to utilize stable flow rate of liquid (internal phase flow velocity 1mL/h) and shearing force
Speed 10mL/h), it is equal that the Ovum Gallus domesticus album solution (aqueous phase) that discontinuous phase is contained medicine by continuous phase soybean oil (oil phase) is cut into size mutually
The Water-In-Oil list emulsion structure of one, during then emulsion injects the collecting pit filling soybean oil by collecting pipe.
3. contain the solidification of the Ovum Gallus domesticus album emulsion of doxorubicin hydrochloride: be placed in by collecting pit on magnetic agitation heater, heating
To 80 DEG C, Ovum Gallus domesticus album emulsion is heated and is occurred degeneration to be solidified into Ovum Gallus domesticus album microsphere, meanwhile, at this temperature to doxorubicin hydrochloride drug effect
Without impact.After collecting pit cools down, by Ovum Gallus domesticus album microsphere sucking-off, and with acetone, anhydrous alcohol, it is thoroughly cleaned successively,
To remove the soybean oil of remained on surface.Finally obtain doxorubicin hydrochloride Ovum Gallus domesticus album medicine microcarrier.Measuring particle diameter is 200 μm, pdi
It is 1.8%.
4. medicament slow release situation observe: prepared Ovum Gallus domesticus album medicine microcarrier is placed in trypsin solution, after 3h every
1h carries out observation and the absorbance measurement of first order fluorescence intensity, and the fluorescence intensity that microcarrier be can be observed gradually weakens, and enzyme
Absorbance in solution gradually strengthens.
Example 2 one kinds Janus based on Ovum Anas domestica album medicine microcarrier preparation method
1. the extraction of Ovum Anas domestica album: with 70% ethanol, fresh Ovum Anas domestica surface is thoroughly cleaned, afterwards with egg device by Ovum Anas domestica album
Separate with Ovum Anas domestica yolk, isolated Ovum Anas domestica album gauze is filtered, take the Ovum Anas domestica album weak solution leached standby.
2. contain the preparation of the Ovum Anas domestica album Janus emulsion of doxorubicin hydrochloride and carboplatin: prepare the micro-fluidic of Ovum Anas domestica album microsphere
Device materials is borosilicate.Internal phase 1 is to be mixed with the Ovum Anas domestica album weak solution that concentration is 1mg/mL doxorubicin hydrochloride, and internal phase 2 is
Being mixed with the Ovum Anas domestica album weak solution that concentration is 0.5mg/mL carboplatin, outer phase material is 200cs methyl-silicone oil.Utilize stable liquid
Flow velocity (internal phase flow velocity 0.5mL/h) and shearing force (foreign minister flow velocity 10mL/h), continuous phase methyl-silicone oil (oil phase) is by discontinuous
I.e. internal phase 1 and internal phase 2(aqueous phase mutually) it is cut into the Water-In-Oil list emulsion structure of size uniformity mutually, then emulsion is injected by collecting pipe
Fill in the collecting pit of methyl-silicone oil.
3. contain the solidification of the Ovum Anas domestica album Janus emulsion of doxorubicin hydrochloride and carboplatin: because of the instantaneous solidification of palpus of Janus emulsion,
So will be placed on magnetic agitation heater by collecting pit before step 2 starts, start again after collecting pit is heated to 80 DEG C
The preparation of emulsion.When Janus emulsion enters in the collecting pit of heating, protein is due to high temperature generation degeneration, thus can realize
The solidification of Janus emulsion.Meanwhile, doxorubicin hydrochloride and carboplatin can't lose pharmaceutically active at this temperature.Afterwards by Ovum Anas domestica
Clear Janus microsphere sucking-off, and with normal hexane, anhydrous alcohol, it is thoroughly cleaned successively, to remove the methyl of remained on surface
Silicone oil.The most i.e. can get doxorubicin hydrochloride-carboplatin Janus Ovum Anas domestica album medicine microcarrier.Measuring particle diameter is 300 μm, and pdi is
1.5%。
4. medicament slow release situation observe: prepared Ovum Gallus domesticus album medicine microcarrier is placed in protease k solution, after 2h every
1h carries out observation and the absorbance measurement of first order fluorescence intensity, and the fluorescence intensity that microcarrier be can be observed gradually weakens, and enzyme
Absorbance in solution gradually strengthens.
Claims (6)
1. a medicine microcarrier based on Ovum Gallus domesticus album, it is characterised in that realize as follows:
(1) extraction of Ovum Gallus domesticus album:
Selected eggs surface is thoroughly cleaned, with egg device, Ovum Gallus domesticus album is separated with egg yolk, the Ovum Gallus domesticus album of isolated is carried out
Filter, take the Ovum Gallus domesticus album weak solution leached standby；
(2) preparation of the Ovum Gallus domesticus album emulsion containing medicine:
Micro fluidic device and the Ovum Gallus domesticus album weak solution containing medicine is utilized to prepare size tunable, uniform Ovum Gallus domesticus album emulsion, Janus
Ovum Gallus domesticus album emulsion, three components or three components above Ovum Gallus domesticus album emulsion；
(3) solidification of the Ovum Gallus domesticus album emulsion containing medicine:
By chemically or physically method, the Ovum Gallus domesticus album emulsion containing medicine is solidified, after cleaning, i.e. can get the micro-load of Ovum Gallus domesticus album medicine
Body；
(4) degraded of Ovum Gallus domesticus album medicine microcarrier:
Ovum Gallus domesticus album medicine microcarrier is placed in certain density enzymatic solution, growth over time, medicine microcarrier be can be observed
Fluorescence gradually weaken, i.e. microcarrier is degraded by enzymes it is achieved thereby that medicament slow release.
Ovum Gallus domesticus album medicine microcarrier the most according to claim 1 and preparation method thereof, it is characterised in that described in step (1)
Ovum Gallus domesticus album takes from chicken, duck, goose, the various birds of Carnis Coturnicis japonicae or the egg ovum of birds.
Ovum Gallus domesticus album medicine microcarrier the most according to claim 1 and preparation method thereof, it is characterised in that described in step (2) by
The Ovum Gallus domesticus album emulsion size containing medicine that microflow control technique prepares is 5 μm-500 μm.
Ovum Gallus domesticus album medicine microcarrier the most according to claim 1 and preparation method thereof, it is characterised in that medicine described in step (2)
Thing is doxorubicin hydrochloride, hydrochloric acid hycamtin, gemcitabine hydrochloride, carboplatin, cytarabine hydrochloride, mustine hydrochlcride, hydrochloric acid rice torr
One or more combination in any in anthraquinone, aspirin, water soluble vitamins.
Ovum Gallus domesticus album medicine microcarrier the most according to claim 1 and preparation method thereof, it is characterised in that described in step (3)
The curing of Ovum Gallus domesticus album emulsion is heating, ultra-vioket radiation, strong acid-base, ethanol degeneration.
Ovum Gallus domesticus album medicine microcarrier the most according to claim 1 and preparation method thereof, it is characterised in that cause described in step (4)
The enzyme making medicine microcarrier degrade can be one or more the combination in any in protease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610978809.0A CN106309383A (en) | 2016-11-08 | 2016-11-08 | Drug microcarrier based on egg white and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610978809.0A CN106309383A (en) | 2016-11-08 | 2016-11-08 | Drug microcarrier based on egg white and preparation method thereof |
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| Publication Number | Publication Date |
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| CN106309383A true CN106309383A (en) | 2017-01-11 |
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ID=57816733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201610978809.0A Pending CN106309383A (en) | 2016-11-08 | 2016-11-08 | Drug microcarrier based on egg white and preparation method thereof |
Country Status (1)
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083770A (en) * | 2014-07-22 | 2014-10-08 | 成都理工大学 | Drug-loaded egg protein microspheres and preparation method thereof |
| CN105879113A (en) * | 2016-06-17 | 2016-08-24 | 东南大学 | Method for preparing three-dimensional cell scaffolds on basis of silk fibroins |
-
2016
- 2016-11-08 CN CN201610978809.0A patent/CN106309383A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083770A (en) * | 2014-07-22 | 2014-10-08 | 成都理工大学 | Drug-loaded egg protein microspheres and preparation method thereof |
| CN105879113A (en) * | 2016-06-17 | 2016-08-24 | 东南大学 | Method for preparing three-dimensional cell scaffolds on basis of silk fibroins |
Non-Patent Citations (2)
| Title |
|---|
| CHANG-SOO LEE等: "Microfluidic System for the Synthesis of Functional Materials", 《PROCEEDINGS OF THE 2010 5TH IEEE INTERNATIONAL CONFERENCE ON NANO/MICRO ENGINEERED AND MOLECULAR SYSTEMS》 * |
| MIN-KYOUNG KIM等: "Capillary microfluidics-derived doxorubicin-containing human serum albumin microbeads for transarterial chemoembolization of hepatic cancer", 《MATERIALS SCIENCE AND ENGINEERING C》 * |
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Application publication date: 20170111 |
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