CN106265599A - The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes - Google Patents
The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes Download PDFInfo
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- CN106265599A CN106265599A CN201610741083.9A CN201610741083A CN106265599A CN 106265599 A CN106265599 A CN 106265599A CN 201610741083 A CN201610741083 A CN 201610741083A CN 106265599 A CN106265599 A CN 106265599A
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- peoniflorin
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- wheat gliadin
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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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
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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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
The invention discloses preparation technology and the purposes of a kind of peoniflorin wheat gliadin nanoparticle.It is by after wheat gluten defat, adds ethanol extraction, and extracting solution concentrates, and lyophilization obtains wheat gliadin；Taking recipe quantity wheat gliadin, peoniflorin, add ethanol and dissolve, alcohol mixture solution is injected into pluronic F68Or in PVA 0486 solution, stirring, obtain colloidal dispersions solution, then carry out lyophilization, i.e. obtain nanometer peoniflorin wheat gliadin nanoparticle.Nano-carrier used by the present invention is edible wheat gliadin, nontoxic, is easy to get, and production cost is low.The peoniflorin wheat gliadin nanoparticle of preparation, individually or can coordinate with other drug and make preparation, improve the absorption in peoniflorin body, the shortcoming overcoming peoniflorin poor bioavailability, can increase substantially the drug effect of peoniflorin, reduces dose.
Description
Technical field
The present invention relates to a kind of method of preparation technology body of peoniflorin wheat gliadin nanoparticle and application thereof.
Technical background
Peoniflorin is the main pharmacodynamics composition of Lactiflora and the Radix Paeoniae Alba, have antiinflammatory, ease pain, the biological activity such as calm the nerves, with
Peoniflorin be the new Chinese medicine Radix Paeoniae Alba total glucosides of principle active component be clinically first for treating rheumatoid arthritis
Anti inflammatory immunity regulating, its treatment R A curative effect is affirmed, untoward reaction is few, but onset is slower.Owing to peoniflorin hydrophilic is relatively strong,
Lipotropy is more weak, and cross-film absorbability is more weak, causes peoniflorin in intestinal absorption difficulty, and bioavailability is low, only 3%-
4%.Peoniflorin oral absorption is poor, not only wastes substantial amounts of drug resource, adds the dose of patient's medicine, commonly simultaneously
Preparation is difficult to the approach that is administered orally and plays its good biological activity in vivo.
Administration nano-drug administration system refers to the medication delivery system of the 1-1000nm that medicine and carrier material use nanotechnology to make
System.Conventional nanometer formulation grain diameter size is many between 10-1000nm.Can lead to as oral drag delivery system nanoparticle
Crossing pcycr ' the s knot of small intestinal and enter blood circulation, the nano-carrier that particle diameter is little may further pass through mesenteric mesaraic iuntercellular path and enters
Enter circulation；Simultaneously because the dispersibility of nanoparticle height and huge surface area, the dissolubility of insoluble drug and molten can be increased
Go out speed, also can increase and the contacting of gastrointestinal tract wall, thus increase the chance of absorption, more can be captured by duodenal microtriche
And it is detained the long period, extend further medicine and cell wall time of contact, improve absorption rate and the absorbance of medicine, improve
The bioavailability of medicine.Therefore, use the medicament nano Oral delivery system that Modern Pharmaceutics means are reasonable in design, be to solve
A kind of effective way of insoluble drug low oral administration biaavailability problem.Wheat gliadin be from Semen Tritici aestivi storage protein with
The molecular weight of ethanol extraction is in a histone matter of 25-100kD.The glutamic acid of its essential amino acid composition about 40% and 14%
Proline, its hydrophobic and hydrophilic amphotericity can produce the hollow ball with liposome vesicle morphological characteristic, for bag
Wrap up in medicine and provide important precondition.It is the pharmaceutical carrier of Novel Drug Delivery Systems, there is pure natural, nontoxic be easy to get, stable
The feature that property is good.
The present invention utilizes the feature of the nano-carrier that wheat gliadin is good, low for peoniflorin bioavailability, difficult
With the shortcoming absorbed, make peoniflorin wheat gliadin nanoparticle, add the absorption in peoniflorin body, for peoniflorin new drug
Research and manufacture provide new method.
Summary of the invention
It is an object of the invention to provide the preparation technology body of a kind of peoniflorin wheat gliadin nanoparticle method and
Purposes.
It is to weigh wheat gluten, adds 3-10 times of percent by volume petroleum ether degreasing twice, and defat gluten adds 5-10 times amount
30%-90% ethanol, supersound extraction 2-4h, centrifugal, supernatant concentration, the dialysis of concentrated solution water is to without tart flavour, and dialysate freezing is done
Dry, obtain wheat gliadin；Weigh the wheat gliadin of recipe quantity: peoniflorin (ratio: 85-95: 5-15).Add appropriate
50%-90% ethanol, ultrasonic making is completely dissolved.Under mechanical agitation, the alcohol mixture solution of gained is injected into 2-5 times
The 0.1%-1% pluronic F of volume68Or in PVA-0486 aqueous solution, stir 5-30min, add 1-5% trehalose, stir
Mix 5-30min, lyophilization, obtain peoniflorin wheat gliadin nanoparticle.Peoniflorin wheat gliadin nanoparticle is permissible
Individually or with other drug coordinate and make corresponding oral formulations, by increasing capacitance it is possible to increase peoniflorin absorbs, and improves its bioavailability.
The described material preparing nanoparticle, preferably wheat alcohol soluble protein: the ratio of peoniflorin is 85-95: 5-15；Aqueous phase
Dispersant selects 0.1%-1% pluronic F68Or PVA-0486 aqueous solution；Peoniflorin wheat gliadin nanoparticle caffolding agent
Select 1-5% trehalose.
The raw material that the present invention uses belongs to pure natural starch material, draws materials easily, low cost；Production technology is simple, can
OK.The peoniflorin wheat gliadin nanoparticle prepared by the method.The peoniflorin wheat gliadin prepared by the method
Nanoparticle can individually or coordinate with other drug makes corresponding oral formulations, by increasing capacitance it is possible to increase peoniflorin absorbs, and improves it raw
Thing availability, for developing the new raw material of peoniflorin medicine.
Detailed description of the invention
Weighing wheat gluten, add 3-10 times of percent by volume petroleum ether degreasing twice, defat gluten adds 5-10 times amount 30%-
90% ethanol, supersound extraction 2-4h, centrifugal, supernatant concentration is to without alcohol taste, and concentrated solution carries out water and dialyses 24 hours, to anacidity
Taste, dialysate first-20 DEG C of pre-freezes 24 hours, then lyophilization 24 hours, obtain wheat gliadin；Weigh the Semen Tritici aestivi of recipe quantity
Alcohol soluble protein: peoniflorin (ratio: 85-95: 5-15).Add the 50%-90% ethanol of 2 times of percents by volume, ultrasonic make completely
Dissolve.Under mechanical agitation, the alcohol mixture solution of gained is injected into the 0.1%-1% pluronic of 2-5 times of volume
F68Or in PVA-0486 aqueous solution, stir 5-30min, and adding 1-5% trehalose, stir 5-30min, 20 DEG C of pre-freezes 24 are little
Time, then lyophilization 24 hours, obtain peoniflorin wheat gliadin nanoparticle.Peoniflorin wheat gliadin nanoparticle is permissible
Individually or with other drug coordinate and make corresponding oral formulations, by increasing capacitance it is possible to increase peoniflorin absorbs, and improves its bioavailability.
The described material preparing nanoparticle, preferably wheat alcohol soluble protein: the ratio of peoniflorin is 85-95: 5-15；Aqueous phase
Dispersant selects 0.1%-1.0% pluronic F68Or PVA-0486 aqueous solution；Peoniflorin wheat gliadin nanoparticle support
1-5% trehalose is selected in agent.
The particle size range using optimization technique to prepare medicine carrying wheat gliadin nanoparticle is 150-250nm, and peoniflorin is little
Gliadin nanoparticle envelop rate is not less than 70%, drug loading 4.0-6.0%.
Embodiment 1:
Weighing wheat gluten, add 5 times of percent by volume petroleum ether degreasings 2 times, defat gluten adds 8 times amount 65% ethanol, super
Sound extraction 2h, centrifugal, supernatant concentration is to without alcohol taste, and concentrated solution carries out water and dialyses 24 hours, to without tart flavour, dialysate first-20
DEG C pre-freeze 24 hours, then lyophilization 24 hours, obtain wheat gliadin；Weigh the wheat gliadin of recipe quantity: Radix Paeoniae
Glycosides (90: 10).Adding 65% ethanol of 2 times of percents by volume, ultrasonic making is completely dissolved.Under mechanical agitation, by gained
Alcohol mixture solution is injected in the 0.3%PVA-0486 aqueous solution of 3 times of volumes, stirs 15min, adds 2% trehalose,
Stirring 20min, 20 DEG C of pre-freezes 24 hours, then lyophilization 24 hours, obtain peoniflorin wheat gliadin nanoparticle.This peoniflorin
The particle size range of wheat gliadin nanoparticle is 200nm, peoniflorin wheat gliadin nanoparticle envelop rate 73%, drug loading
4.6%.
Experimental example 2:
Weighing wheat gluten, add 6 times of percent by volume petroleum ether degreasings 2 times, defat gluten adds 7 times amount 80% ethanol, super
Sound extraction 3h, centrifugal, supernatant concentration is to without alcohol taste, and concentrated solution carries out water and dialyses 24 hours, to without tart flavour, dialysate first-20
DEG C pre-freeze 24 hours, then lyophilization 24 hours, obtain wheat gliadin；Weigh the wheat gliadin of recipe quantity: Radix Paeoniae
Glycosides (85: 15).Adding 85% ethanol of 2 times of percents by volume, ultrasonic making is completely dissolved.Under mechanical agitation, by gained
Alcohol mixture solution is injected into 0.5% pluronic F of 4 times of volumes68In aqueous solution, stir 10min, add 4% Sargassum
Sugar, stirs 10min, 20 DEG C of pre-freezes 24 hours, then lyophilization 24 hours, obtains peoniflorin wheat gliadin nanoparticle.This Chinese herbaceous peony
The particle size range of medicine glycosides wheat gliadin nanoparticle is 180nm, peoniflorin wheat gliadin nanoparticle envelop rate 83%, carries
Dose 6.1%.
Embodiment 3
Weighing wheat gluten, add 9 times of percent by volume petroleum ether degreasings twice, defat gluten adds 6 times amount 40% ethanol, super
Sound extraction 2h, centrifugal, supernatant concentration is to without alcohol taste, and concentrated solution carries out water and dialyses 24 hours, to without tart flavour, dialysate first-20
DEG C pre-freeze 24 hours, then lyophilization 24 hours, obtain wheat gliadin；Weigh the wheat gliadin of recipe quantity: Radix Paeoniae
Glycosides (ratio: 93: 7).Adding 50% ethanol of 2 times of percents by volume, ultrasonic making is completely dissolved.Under mechanical agitation, by institute
The alcohol mixture solution obtained is injected into 0.2% pluronic F of 2 times of volumes68In aqueous solution, stir 5min, add 2% sea
Algae sugar, stirs 5min, 20 DEG C of pre-freezes 24 hours, then lyophilization 24 hours, obtains peoniflorin wheat gliadin nanoparticle.This Chinese herbaceous peony
The particle size range of medicine glycosides wheat gliadin nanoparticle is 220nm, peoniflorin wheat gliadin nanoparticle envelop rate 87%, carries
Dose 4.3%.
Prepared peoniflorin wheat gliadin nanoparticle pharmaceutical properties
1, the morphologic observation of peoniflorin wheat gliadin nanoparticle
Take peoniflorin wheat gliadin nanoparticle colloidal dispersion, drip on the copper mesh covering carbon film, with 2% phosphorus tungsten
Acid sodium negative staining liquid dyeing, shoots transmission electron microscope photo, homogeneous sized by the peoniflorin wheat gliadin nanoparticle sample of preparation,
Subsphaeroidal particle.
2, peoniflorin wheat gliadin nanoparticle tablets in vitro test
Employing dynamic dialysis technology carries out the research of the tablets in vitro rule of peoniflorin wheat gliadin nanoparticle, Radix Paeoniae
Glycosides is with wheat gliadin nanoparticle as carrier, and the rate of release in gastric juice is faster than the release in simulated intestinal fluid.Gastric juice,
In intestinal juice and three kinds of release medium of normal saline all the highest with weibull equation model goodness.
Claims (5)
1. the preparation technology of a peoniflorin wheat gliadin nanoparticle and purposes, it is characterised in that: weigh wheat gluten, add 3-
10 times of percent by volume petroleum ether degreasings twice, defat gluten adds 5-10 times amount 30%-90% ethanol, supersound extraction 2-4h,
Centrifugal, supernatant concentration, the dialysis of concentrated solution water, to without tart flavour, dialysate lyophilization, obtains wheat gliadin；Weigh prescription
The wheat gliadin of amount: peoniflorin (ratio 85-95: 5-15).Adding appropriate 50%-90% ethanol, ultrasonic making is completely dissolved.
Under mechanical agitation, the alcohol mixture solution of gained is injected into the 0.1%-1% pluronic F of 2-5 times of volume68Or
In PVA-0486 aqueous solution, stir 5-30min, add 1-5% trehalose, stir 5-30min, lyophilization, obtain Radix Paeoniae
Glycosides wheat gliadin nanoparticle.Peoniflorin wheat gliadin nanoparticle can individually or be made corresponding to other drug cooperation
Oral formulations, by increasing capacitance it is possible to increase peoniflorin absorb, improve its bioavailability.
The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle the most according to claim 1, it is characterised in that: system
The material of standby nanoparticle, wheat gliadin: the ratio of peoniflorin is: 85-95: 5-15.
The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle the most according to claim 1, it is characterised in that: system
0.1%-1% pluronic F is selected in standby peoniflorin wheat gliadin nanoparticle Aqueous dispersions agent68Or PVA-0486 aqueous solution.
The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle the most according to claim 1, it is characterised in that: Chinese herbaceous peony
Medicine glycosides wheat gliadin nanoparticle caffolding agent selects 1-5% trehalose.
5. the purposes of an a kind of peoniflorin wheat gliadin nanoparticle as claimed in claim 1, it is characterised in that: permissible
Individually or with other drug coordinate and make corresponding oral formulations, by increasing capacitance it is possible to increase peoniflorin absorbs, and improves its bioavailability.
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| CN201610741083.9A CN106265599A (en) | 2016-08-29 | 2016-08-29 | The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes |
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| CN201610741083.9A CN106265599A (en) | 2016-08-29 | 2016-08-29 | The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108567763A (en) * | 2018-06-12 | 2018-09-25 | 广州中医药大学(广州中医药研究院) | A kind of Paeoniflorin nanocrystal and preparation method thereof |
| CN112245409A (en) * | 2020-10-23 | 2021-01-22 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
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| CN103734742A (en) * | 2014-01-24 | 2014-04-23 | 上海理工大学 | Polyphenols-hordein nanoparticle and preparation method thereof |
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| CN101317832A (en) * | 2007-06-06 | 2008-12-10 | 周亚伟 | Oral administration nano-drug administration system of resveratrol |
| CN103813786A (en) * | 2011-02-25 | 2014-05-21 | 南达科他州立大学 | Protein nanocarriers for topical delivery |
| KR20130104534A (en) * | 2012-03-14 | 2013-09-25 | 한양대학교 에리카산학협력단 | Preparation method for gliadin nanoparticles by electrospray |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108567763A (en) * | 2018-06-12 | 2018-09-25 | 广州中医药大学(广州中医药研究院) | A kind of Paeoniflorin nanocrystal and preparation method thereof |
| CN112245409A (en) * | 2020-10-23 | 2021-01-22 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
| CN112245409B (en) * | 2020-10-23 | 2022-03-15 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
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Application publication date: 20170104 |