CN108653239A - A kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparation and preparation method thereof - Google Patents
A kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN108653239A CN108653239A CN201810643329.8A CN201810643329A CN108653239A CN 108653239 A CN108653239 A CN 108653239A CN 201810643329 A CN201810643329 A CN 201810643329A CN 108653239 A CN108653239 A CN 108653239A
- Authority
- CN
- China
- Prior art keywords
- egcg
- epigallo
- catechin gallate
- preparation
- release preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- A61K9/5138—Organic macromolecular compounds; Dendrimers 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparation and preparation method thereof, Epigallo-catechin gallate (EGCG) nano controlled-release preparation includes being wrapped drug Epigallo-catechin gallate (EGCG) and lapping n-butyl polycyanoacrylate.The preparation method of Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention, without using water and acetone system, there is no the problem of acetone solvent residual, the adjusting of pH and the intervention of other processes are not needed, its is simple for process, at low cost, reaction condition requirement is low, not only brings economic benefit, environment protection significance, also there is prodigious social benefit, there is very high application prospect.
Description
Technical field
The present invention relates to a kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparations and preparation method thereof.
Background technology
Epigallo-catechin gallate (EGCG) ((-)-Epigallocatechin-3-O-gallate, EGCG) is from green
Isolated catechin monomeric substance, content account for 50% of tea polyphenols or so in tea, there is that researches show that epigallocatechin gallates
The bioactivity of catechin gallate and pharmacological action are all stronger.In recent years, as the research to catechin is more and more wider
General, Epigallo-catechin gallate (EGCG) is also constantly going deep into, since it has its anti-aging, anticancer, anti-inflammatory, antioxygen
Change the pharmacological actions such as anti-removing free radical, at present in the fields such as biomedicine, health care, food industry, daily-use chemical industry are studied carefully
Highly important effect is shown, application prospect will be very considerable.
But Epigallo-catechin gallate (EGCG) property is very unstable, be easy light, oxygen, temperature, pH etc. it is extraneous because
Element influence and change, Epigallo-catechin gallate (EGCG) is easy to be degraded, and bioavailability is extremely low.Nanometer medicine
Object technology has been widely used, and compared with traditional drug, is had higher bioavailability, dissolubility, targeting, can be improved
The drug effect of drug is forward position and the hot spot of medical research.In recent years, also epi-nutgall has been prepared for there are many researcher
Catechin and gallate nanometer formulation, as chitosan wraps up Epigallo-catechin gallate (EGCG) nanoparticle, beta-globin
Epigallo-catechin gallate (EGCG) nanoparticle is wrapped up, cadmium sulfide wraps up Epigallo-catechin gallate (EGCG) nanoparticle,
The grain size that these lappings are formed by nanoparticle Epigallo-catechin gallate (EGCG) nanoparticle is bigger, and grain size is viscous
Even, unstable, and the preparation prepared cannot take orally, also lapping has toxicity (such as metal material) or carrier material high
It is expensive, and their preparation process is complicated, and there may be poisonous and harmful substances etc. for preparation condition requirement harshness and preparation process no
Foot.These strictly limit their application.
Invention content
Technical problem to be solved by the invention is to provide a kind of nontoxic, good biocompatibility, biological degradability is good
Epigallo-catechin gallate (EGCG) nano controlled-release preparation and preparation method thereof.
In order to solve the above-mentioned technical problem, the present invention adopts the following technical scheme that：A kind of epigallocatechin nutgall
Acid esters nano controlled-release preparation, including it is wrapped drug Epigallo-catechin gallate (EGCG) and the poly- alpha-cyanoacrylate of lapping
N-butyl.
Further, the grain size of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation is 30~40 nanometers.
Further, the encapsulation rate of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation be 70.73~
80.15%.
The present invention provides a kind of preparation method of above-mentioned Epigallo-catechin gallate (EGCG) nano controlled-release preparation, including
Following steps：
(1) raw material is prepared
Prepare oil phase raw material：Disperse α-cyanoacrylaten-butyl in ethyl acetate；
Prepare Emulsion Phase raw material：Dispersion emulsifier and stabilizer in ultra-pure water；
(2) polymerisation
Polymerisation selects interface polymerization reaction or emulsion polymerization reaction；
The process of interface polymerization reaction is：Epigallo-catechin gallate (EGCG) is added in oil phase raw material, is obtained
Then mixture I is added gradually to carry out interface polymerization reaction in Emulsion Phase raw material by mixture I；
Emulsion polymerization reaction process be：Epigallo-catechin gallate (EGCG) is added in Emulsion Phase raw material, is obtained
To mixture II, then oil phase raw material is added gradually to carry out emulsion polymerization reaction in mixture II.
Further, the emulsifier is poloxamer -68, and the stabilizer is dextran -70.Implementing the present invention
During, inventor has found to use both specific raw materials, can ensure that α-cyanoacrylaten-butyl fully reacts, and
Nontoxic, in addition poloxamer -68 is a kind of emulsifier being suitable for preparing injection, is conducive to be subsequently used for injecting in this way
The exploitation of agent.
Further, 20~40 milligrams of emulsifier, 45~55 milligrams of stabilizer are dispersed in every 5 milliliters of ultra-pure waters.In reality
During applying the present invention, inventor has found, within the scope of this, Epigallo-catechin gallate (EGCG) nanometer obtained is slow
Release formulation particle diameter is smaller, distribution is uniform, and is less than above range, then the nanoparticle grain size formed is bigger than normal and inhomogenous, high
In above range, then auxiliary material accounts for excessive proportion, wastes raw material.
Further, it is micro- to be dispersed with α-cyanoacrylaten-butyl 8~17 in oil phase raw material, in every 1 milliliter of ethyl acetate
It rises.In implementing the present invention, it may, inventor has found, it is less than above range, epigallocatechin gallic acid obtained
Ester nano controlled-release preparation encapsulation rate is relatively low, is higher than above range, polymerisation is incomplete, can also waste monomer material.
Further, the dosage volume of oil phase raw material and Emulsion Phase raw material in interface polymerization reaction or emulsion polymerization reaction
Than being 5：1.In implementing the present invention, it may, inventor has found that, using this ratio, reaction efficiency higher can ensure
Reaction fully carries out, and is conveniently operated.
Further, the mass volume ratio of Epigallo-catechin gallate (EGCG) and α-cyanoacrylaten-butyl is 1
~8 milligrams：8~17 microlitres.In implementing the present invention, it may, inventor has found, and using this ratio, reaction efficiency higher,
Wastage of material is few, and can guarantee particle size at 30~40 nanometers, and encapsulation rate is 70.73~80.15%.
Further, in interface polymerization reaction or emulsion polymerization reaction, mixture I is added gradually in Emulsion Phase raw material
And oil phase raw material be added gradually to the instillation total time in mixture II be 4~8 minutes.
Further, it in interface polymerization reaction or emulsion polymerization reaction, is carried out with 800~950 rpms of rotating speed
Magnetic agitation.In implementing the present invention, it may, inventor has found, using this condition can make the nanoparticulate particles of preparation compared with
It is small, be evenly distributed.
Further during interface polymerization reaction, the quality of Epigallo-catechin gallate (EGCG) in mixture I
A concentration of 1~8g/L, during emulsion polymerization reacts, the quality of Epigallo-catechin gallate (EGCG) is dense in mixture II
Degree is 0.2~1.6g/L.If concentration is too low, drug is very few, waste package monomer, and excessive concentration, then can lead to encapsulation rate
It is too low, in implementing the present invention, it may, inventor has found, in above range, it not only can guarantee encapsulation rate, but also can guarantee utilization
Rate.
Further, the time of interface polymerization reaction and emulsion polymerization reaction is 2.5~3.5 hours.Implementing this hair
Bright process, inventor have found that this range can ensure that reaction is abundant.
Further, further comprising the steps of：
(3) it post-processes
After polymerisation, organic solvent is first removed, then by obtaining epi-nutgall catechu after agitated processing and filtering
The suspension of plain gallate nano controlled-release preparation, or Epigallo-catechin gallate (EGCG) is made by freeze-drying
The freeze-dried powder of nano controlled-release preparation.
Further, in step (3), it is 800~950 rpms that stir process, which uses magnetic agitation, rotating speed, and the time is
Half an hour, filtering use aperture for 2~5 microns of filter paper.After removing organic solvent, it is to ensure to gather to be stirred for half an hour
The reaction was complete for conjunction, and it is to remove some floccules generated in the polymerization to be filtered.
Further, remove organic phase by under the conditions of 30~40 DEG C rotary evaporation in vacuo remove.Can prevent not by
The EGCG of package is by high-temperature oxydation.
The present invention also provides a kind of drug, including above-mentioned Epigallo-catechin gallate (EGCG) nano controlled-release preparation and auxiliary
Material.The drug can be made into the drugs common dosage forms such as tablet, injection, suppository, pill, belong to the protection category of the present invention.Tool
Prepared by the conventional method that preparation can refer to pharmaceutical field, auxiliary material used can select pharmaceutical field general according to dosage form difference
Auxiliary material.It, can be directly in the mixed of prepared Epigallo-catechin gallate (EGCG) nano controlled-release preparation in specific implementation
Medicine or food auxiliary material appropriate is added in suspension or freeze-dried powder, you can be made it is any can hyoscine or food effect dosage form or material
Material.
Beneficial effects of the present invention are embodied in：
Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention utilizes the positive fourth of poly- alpha-cyanoacrylate
Ester biological compatibility is good, and biological degradability is good, the advantage of the aspect of performance such as hypotoxicity and prepare nontoxic, biocompatibility
It is good, the good nanoparticle of biological degradability, and Epigallo-catechin gallate (EGCG) can slow release, it is more extensive to obtain
Biomedical applications.
Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention is a kind of nanoparticle, available to receive
The small advantage of rice size is applied in the field of many very small dimensions grades, for filling for Epigallo-catechin gallate (EGCG)
Development and application are divided to provide more convenient foreground.
The preparation method of Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention, without using water and
Acetone system, the problem of residual without acetone solvent, do not need pH adjusting and other processes intervention, it is simple for process, at
This is low, reaction condition requirement is low, not only brings economic benefit, environment protection significance also to have prodigious social benefit, has very high
Application prospect.
The preparation method of Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention can be prepared into
It it is 30~40 nanometers to grain size, PDI is 0.09~0.3, and electromotive force is -13.47 ± 7.50~-29.52 ± 4.68mV, encapsulation rate
It is 70.73~80.15%, the Epigallo-catechin gallate (EGCG) nano controlled-release preparation for no adhesion that is uniformly dispersed.
The present invention, that any poisonous and hazardous material is not added, does not have from the source of raw material and entire production process yet
Have and generates any poisonous and hazardous substance.And pharmacopeia in 2015 wants organic solvent ethyl acetate solvent residual without very stringent
It asks, even the appearance agent residual of organic solvent ethyl acetate is also non-toxic.So epigallocatechin prepared by the present invention is not eaten
Sub- acid esters nano controlled-release preparation has good biocompatibility and without any side effects, as medical bio nanometer formulation or drug
Targeted delivery preparation has good development prospect.And dissolvent residual can be used as the preparation produced extensively without limitation.
Epigallo-catechin gallate (EGCG) nano controlled-release preparation provided by the invention can be injected, takes orally, be smeared
Equal sustained release preparations utilize pharmacological activity itself and the n-butyl polycyanoacrylate biology of Epigallo-catechin gallate (EGCG)
Compatibility can be used for the treatment of human body or the various diseases of animal.
Description of the drawings
Fig. 1 is the scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 1；
Fig. 2 is the transmission electron microscope picture of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 1.
Fig. 3 is the grain size distribution of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 1.
Fig. 4 is that the X of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 1 and embodiment 7 is penetrated
Ray diffraction diagram.
Fig. 5 is the release test result figure of embodiment 8.
Specific implementation mode
It is next below with reference to the accompanying drawings that the present invention will be described in detail.It should be noted that in the absence of conflict, in the application
Embodiment and embodiment in feature can be combined with each other.
Embodiment 1
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 17 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 25 milligrams of poloxamer -68 and 50 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 2 milligrams of Epigallo-catechin gallate (EGCG)s and is added in oil phase raw material, and shake mixing is even uniformly,
Mixture I is obtained, then mixture I is added dropwise in 6 minutes in Emulsion Phase raw material dropwise and carries out interface polymerization reaction, is reacted
It is carried out under the magnetic agitation of 850 rpms of rotating speed, the total time of reaction is 3 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 35 DEG C, then through magnetic agitation in half an hour, filtering
The suspension of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is obtained afterwards, wherein magnetic agitation rotating speed is 800 turns every
Minute, when filtering, uses aperture for 4 microns of filter paper.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is shown in Fig. 1,
Transmission electron microscope (TEM) figure is shown in that Fig. 2, grain size audio-visual picture are shown in that Fig. 3, X-ray diffractogram are shown in Fig. 4.
It can obtain, Epigallo-catechin gallate (EGCG) nano controlled-release preparation grain size made from the present embodiment is small, grain
Son is spherical in shape, and 30~40 nanometers of size is evenly distributed, well dispersed, no particle adhesion phenomenon, encapsulation rate 77.82%.
In Fig. 4, A is the X-ray diffraction of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 1
Figure, C be blank poly-alkyl-alfa-cyanoacrylate nanoparticles X-ray diffractogram, D be Epigallo-catechin gallate (EGCG) with
The X-ray diffractogram of the physical mixture of blank poly-alkyl-alfa-cyanoacrylate nanoparticles, E are epigallocatechin nutgall
The X-ray diffractogram of acid esters.Figure 4, it can be seen that if Epigallo-catechin gallate (EGCG) is not wrapped, characteristic peak meeting
Occur the characteristic peak in E as shown atd but since drug concentration is relatively low, characteristic diffraction peak intensity is smaller.And it is anti-to pass through polymerization
Answer the characteristic diffraction peak that Epigallo-catechin gallate (EGCG) has not been observed in the X-ray peak of embodiment 1 obtained, explanation
In the present embodiment, Epigallo-catechin gallate (EGCG) is fully wrapped up.
Embodiment 2
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 10 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 25 milligrams of poloxamer -68 and 50 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 1 milligram of Epigallo-catechin gallate (EGCG) and is added in oil phase raw material, and shake mixing is even uniformly,
Mixture I is obtained, then mixture I is added dropwise in 4 minutes in Emulsion Phase raw material dropwise and carries out interface polymerization reaction, is reacted
It is carried out under the magnetic agitation of 800 rpms of rotating speed, the total time of reaction is 3.5 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 30 DEG C, then through magnetic agitation in half an hour, filtering
The suspension of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is obtained afterwards, wherein magnetic agitation rotating speed is 950 turns every
Minute, when filtering, uses aperture for 2 microns of filter paper.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure, grain size audio-visual picture and X-ray diffractogram are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 80.15%.
Embodiment 3
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 15 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 20 milligrams of poloxamer -68 and 45 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 2 milligrams of Epigallo-catechin gallate (EGCG)s and is added in oil phase raw material, and shake mixing is even uniformly,
Mixture I is obtained, then mixture I is added dropwise in 8 minutes in Emulsion Phase raw material dropwise and carries out interface polymerization reaction, is reacted
It is carried out under the magnetic agitation of 900 rpms of rotating speed, the total time of reaction is 2.5 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 40 DEG C, then through magnetic agitation in half an hour, filtering
The suspension of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is obtained afterwards, wherein magnetic agitation rotating speed is 850 turns every
Minute, when filtering, uses aperture for 3 microns of filter paper.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure, grain size audio-visual picture and X-ray diffractogram are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 76.95%.
Embodiment 4
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 8 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 35 milligrams of poloxamer -68 and 50 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 4 milligrams of Epigallo-catechin gallate (EGCG)s and is added in Emulsion Phase raw material, and it is even to shake mixing
It is even, mixture II is obtained, then oil phase raw material is added dropwise in 4 minutes in mixture II dropwise and carries out interface polymerization reaction,
It reacts and is carried out under the magnetic agitation of 950 rpms of rotating speed, the total time of reaction is 2.5 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 38 DEG C, then freezes under the conditions of -80 DEG C, and pass through
It crosses freeze-drying in 48 hours and the freeze-dried powder of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is made.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure, grain size audio-visual picture and X-ray diffractogram are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 74.91%.
Embodiment 5
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 10 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 25 milligrams of poloxamer -68 and 55 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 6 milligrams of Epigallo-catechin gallate (EGCG)s and is added in Emulsion Phase raw material, and it is even to shake mixing
It is even, mixture II is obtained, then oil phase raw material is added dropwise in mixture II dropwise in 5 minutes and carries out interface polymerization reaction,
It reacts and is carried out under the magnetic agitation of 800 rpms of rotating speed, the total time of reaction is 3 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 38 DEG C, then freezes under the conditions of -80 DEG C, and pass through
It crosses freeze-drying in 48 hours and the freeze-dried powder of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is made.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure, grain size audio-visual picture and X-ray diffractogram are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 72.88%.
Embodiment 6
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 10 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 40 milligrams of poloxamer -68 and 45 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 8 milligrams of Epigallo-catechin gallate (EGCG)s and is added in Emulsion Phase raw material, and it is even to shake mixing
It is even, mixture II is obtained, then oil phase raw material is added dropwise in 8 minutes in mixture II dropwise and carries out interface polymerization reaction,
It reacts and is carried out under the magnetic agitation of 950 rpms of rotating speed, the total time of reaction is 3.5 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 30 DEG C, then freezes under the conditions of -80 DEG C, and pass through
It crosses freeze-drying in 48 hours and the freeze-dried powder of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is made.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure, grain size audio-visual picture and X-ray diffractogram are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 70.73%.
It is observed under scanning electron microscope and transmission electron microscope, epigallocatechin made from embodiment 1 to 6
Gallate nano controlled-release preparation grain size is small, and particle is spherical in shape, is evenly distributed, is well dispersed, no particle adhesion phenomenon；Through grain
It spends analyzer to analyze, the grain size of Epigallo-catechin gallate (EGCG) nano controlled-release formulation products made from embodiment 1 to 6 is
30~40 nanometers, electromotive force is -13.47 ± 7.50~-29.52 ± 4.68mV.
Embodiment 7
The preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
Preparation method includes the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Evenly dispersed 17 microlitres of the α-cyanoacrylaten-butyl in 1 milliliter of ethyl acetate；
Prepare Emulsion Phase raw material：Evenly dispersed 25 milligrams of poloxamer -68 and 50 milligrams of the right side in 5 milliliters of ultra-pure waters
Glucosides -70 is revolved, at room temperature, ultrasonic dissolution is uniformly mixed；
(2) polymerisation
Precision weighs 2 milligrams of Epigallo-catechin gallate (EGCG)s and is added in Emulsion Phase raw material, and it is even to shake mixing
It is even, mixture II is obtained, then oil phase raw material is added dropwise in 6 minutes in mixture II dropwise and carries out interface polymerization reaction,
It reacts and is carried out under the magnetic agitation of 850 rpms of rotating speed, the total time of reaction is 3 hours；
(3) it post-processes
After polymerisation, first evaporating organic solvent under the conditions of 35 DEG C, then through magnetic agitation in half an hour, filtering
The suspension of Epigallo-catechin gallate (EGCG) nano controlled-release preparation is obtained afterwards, wherein magnetic agitation rotating speed is 800 turns every
Minute, when filtering, uses aperture for 4 microns of filter paper.
The scanning electron microscope (SEM) photograph of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment, transmission electricity
Mirror (TEM) figure and grain size audio-visual picture are similar to Example 1, no longer superfluous to show for the sake of succinct description.
The particle of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from the present embodiment is spherical in shape, and distribution is equal
It is even, well dispersed, no particle adhesion phenomenon, encapsulation rate 77.24%.
In Fig. 4, B is the X-ray diffraction of Epigallo-catechin gallate (EGCG) nano controlled-release preparation made from embodiment 7
Figure, equally can be seen that, the present embodiment Epigallo-catechin gallate (EGCG) is fully wrapped up from Fig. 4.
Embodiment 8
The release test of Epigallo-catechin gallate (EGCG) nano controlled-release preparation
To contain the ascorbic PBS salt buffers (pH 7.4) of 20mM for dissolution medium, accurately weighs 2.0 milligrams of tables and do not have
Infanticide catechin and gallate is uniformly mixed with 10 milliliters of dissolution mediums, and embodiment 1 (uses EGCG nanoparticles (oil) table in figure
Show) and the obtained Epigallo-catechin gallate (EGCG) nano controlled-release of embodiment 7 (in figure with EGCG nanoparticles (water) indicate)
Total volume is 10 milliliters to the suspension of preparation after evenly mixing with dissolution medium, is transferred to processed through EDTA solution and ultra-pure water
In bag filter, bag filter both ends are tightened, are tied on slurry, is respectively placed in the dissolution bottle for filling 30 milliliters of dissolution mediums, in perseverance
Constant speed is shaken in warm (37 DEG C) shaking table (100r/min).
Respectively at 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 9 hours, 13 hours, 20 hours, 28 hours, 36 is small
When, 1 milliliter of sampling in 48 hours is set 4 DEG C of refrigerator freezings and is preserved, and 1 milliliter of dissolution medium solution is supplemented after every sub-sampling, by institute
It takes sample to be centrifuged 30 minutes for 18000 revs/min, 4 DEG C through high speed low temperature centrifugal machine, takes 0.8 milliliter of supernatant micro- through 0.45 micron
Hole membrane filtration, takes subsequent filtrate.
Different time points Sample supernatants liquid hold-up is measured using HPLC methods, each sample introduction 10u L measure epi-nutgall catechu
The peak area of plain gallate, and the concentration of standard curve regression equation calculation Epigallo-catechin gallate (EGCG) is pressed,
It obtains cumulative release percentage and draws drug release profiles, experimental result is as shown in Figure 5.
It delays the result shows that reacting obtained Epigallo-catechin gallate (EGCG) nanometer using interface/emulsion polymerization
Release formulation and Epigallo-catechin gallate (EGCG) itself release are compared the effect for all having slow release, and interface
The effect of the slow release of Epigallo-catechin gallate (EGCG) nano controlled-release preparation prepared by polymerisation is slightly better than breast
Change the Epigallo-catechin gallate (EGCG) nano controlled-release preparation prepared by polymerisation.
It should be understood that example as described herein and embodiment are not intended to restrict the invention, this field only for explanation
Technical staff can make various modifications or variation according to it, all within the spirits and principles of the present invention, made by it is any modification,
Equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparation, it is characterised in that：Do not have including being wrapped drug table
Infanticide catechin and gallate and lapping n-butyl polycyanoacrylate.
2. Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 1, it is characterised in that：The table
The grain size of nutgall catechin gallic acid ester nano controlled-release preparation is 30~40 nanometers.
3. Epigallo-catechin gallate (EGCG) nano controlled-release preparation as claimed in claim 1 or 2, it is characterised in that：Institute
The encapsulation rate for stating Epigallo-catechin gallate (EGCG) nano controlled-release preparation is 70.73~80.15%.
4. a kind of drug, it is characterised in that：It is not eaten including epigallocatechin as claimed any one in claims 1 to 3
Sub- acid esters nano controlled-release preparation and auxiliary material.
5. the preparation of Epigallo-catechin gallate (EGCG) nano controlled-release preparation as claimed any one in claims 1 to 3
Method, it is characterised in that：Include the following steps：
(1) raw material is prepared
Prepare oil phase raw material：Disperse α-cyanoacrylaten-butyl in ethyl acetate；
Prepare Emulsion Phase raw material：Dispersion emulsifier and stabilizer in ultra-pure water；
(2) polymerisation
Polymerisation selects interface polymerization reaction or emulsion polymerization reaction；
The process of interface polymerization reaction is：Epigallo-catechin gallate (EGCG) is added in oil phase raw material, is mixed
Then mixture I is added gradually to carry out interface polymerization reaction in Emulsion Phase raw material by object I；
Emulsion polymerization reaction process be：Epigallo-catechin gallate (EGCG) is added in Emulsion Phase raw material, is mixed
Object II is closed, is then added gradually to oil phase raw material to carry out emulsion polymerization reaction in mixture II.
6. the preparation method of Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 5, special
Sign is：The emulsifier is poloxamer -68, and the stabilizer is dextran -70.
7. the preparation method of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 5 or 6,
It is characterized in that：In Emulsion Phase raw material, 20~40 milligrams of emulsifier, 45~55 milligrams of stabilizer are dispersed in every 5 milliliters of ultra-pure waters.
8. the preparation method of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 5 or 6,
It is characterized in that：In oil phase raw material, 8~17 microlitres of α-cyanoacrylaten-butyl is dispersed in every 1 milliliter of ethyl acetate.
9. the preparation method of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 5 or 6,
It is characterized in that：During interface polymerization reaction, the mass concentration of Epigallo-catechin gallate (EGCG) is 1 in mixture I
~8g/L, during emulsion polymerization reacts, the mass concentration of Epigallo-catechin gallate (EGCG) is 0.2 in mixture II
~1.6g/L.
10. the preparation method of the Epigallo-catechin gallate (EGCG) nano controlled-release preparation as described in claim 5 or 6,
It is characterized in that：The time of interface polymerization reaction and emulsion polymerization reaction is 2.5~3.5 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810643329.8A CN108653239B (en) | 2018-06-21 | 2018-06-21 | Epigallocatechin gallate nano sustained-release preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810643329.8A CN108653239B (en) | 2018-06-21 | 2018-06-21 | Epigallocatechin gallate nano sustained-release preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108653239A true CN108653239A (en) | 2018-10-16 |
| CN108653239B CN108653239B (en) | 2020-01-24 |
Family
ID=63772637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810643329.8A Active CN108653239B (en) | 2018-06-21 | 2018-06-21 | Epigallocatechin gallate nano sustained-release preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108653239B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453265A (en) * | 2018-10-17 | 2019-03-12 | 安徽农业大学 | A kind of n-butyl polycyanoacrylate package Nano-Zinc green tea sustained release preparation and its application |
| CN113876738A (en) * | 2021-09-29 | 2022-01-04 | 安徽理工大学 | Safe and effective quercetin nanometer sustained-release preparation for resisting silicon-dust pulmonary fibrosis and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104273521A (en) * | 2013-07-03 | 2015-01-14 | 江南大学 | Glycosylated casein-based tea polyphenol nano capsule and preparation method thereof |
| CN104605228A (en) * | 2015-01-29 | 2015-05-13 | 安徽农业大学 | EGCG chitosan/beta-lactoglobulin composite nanoparticles and preparation method thereof |
| CN105663085A (en) * | 2016-03-11 | 2016-06-15 | 安徽农业大学 | Paeonol nanometer sustained release preparation and preparation method thereof |
| CN105820277A (en) * | 2016-04-29 | 2016-08-03 | 安徽农业大学 | Preparation method of polybutylcyanoacrylate nanowire |
-
2018
- 2018-06-21 CN CN201810643329.8A patent/CN108653239B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104273521A (en) * | 2013-07-03 | 2015-01-14 | 江南大学 | Glycosylated casein-based tea polyphenol nano capsule and preparation method thereof |
| CN104605228A (en) * | 2015-01-29 | 2015-05-13 | 安徽农业大学 | EGCG chitosan/beta-lactoglobulin composite nanoparticles and preparation method thereof |
| CN105663085A (en) * | 2016-03-11 | 2016-06-15 | 安徽农业大学 | Paeonol nanometer sustained release preparation and preparation method thereof |
| CN105820277A (en) * | 2016-04-29 | 2016-08-03 | 安徽农业大学 | Preparation method of polybutylcyanoacrylate nanowire |
Non-Patent Citations (4)
| Title |
|---|
| CHENYU CHU ET AL: "Evaluation of nanohydroxyapaptite (nano-HA) coated epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes", 《MATERIALS SCIENCE AND ENGINEERING C》 * |
| 侯绍云等: "EGCG-CS-PAA纳米粒制备及其稳定性实验研究", 《食品工业科技》 * |
| 孙 静等: "表没食子儿茶素没食子酸酯壳聚糖纳米粒的制备及其药剂学性质研究", 《中草药》 * |
| 梅兴国主编: "《微载体药物递送系统》", 30 November 2009, 华中科技大学出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453265A (en) * | 2018-10-17 | 2019-03-12 | 安徽农业大学 | A kind of n-butyl polycyanoacrylate package Nano-Zinc green tea sustained release preparation and its application |
| CN109453265B (en) * | 2018-10-17 | 2021-07-16 | 安徽农业大学 | Nano zinc green tea sustained release preparation wrapped by poly n-butyl cyanoacrylate and application thereof |
| CN113876738A (en) * | 2021-09-29 | 2022-01-04 | 安徽理工大学 | Safe and effective quercetin nanometer sustained-release preparation for resisting silicon-dust pulmonary fibrosis and preparation method thereof |
| CN113876738B (en) * | 2021-09-29 | 2023-12-22 | 安徽理工大学 | A quercetin nanometer slow release preparation for safely and effectively resisting pneumoconiosis fibrosis, and its preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108653239B (en) | 2020-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Fabrication of sustained-release zein nanoparticles via modified coaxial electrospraying | |
| Lengert et al. | Silver alginate hydrogel micro-and nanocontainers for theranostics: synthesis, encapsulation, remote release, and detection | |
| Oliveira et al. | Spray-dried chitosan microspheres cross-linked with d, l-glyceraldehyde as a potential drug delivery system: preparation and characterization | |
| DE112006004066B4 (en) | A magnetic carrier and medical preparation for controllably delivering and releasing drugs, methods of preparation thereof, and methods of treatment using the same | |
| Safer et al. | Conjugation of EGCG and chitosan NPs as a novel nano-drug delivery system | |
| Gao et al. | Recent advances in microfluidic-aided chitosan-based multifunctional materials for biomedical applications | |
| Liu et al. | Incorporation of 10-hydroxycamptothecin nanocrystals into zein microspheres | |
| Wang et al. | Preparation, characterization and applications of low-molecular-weight alginate–oligochitosan nanocapsules | |
| KR20190010212A (en) | Method for preparation of resveratrol nano-capsue and the nano-capsule therefrom | |
| CN108653239A (en) | A kind of Epigallo-catechin gallate (EGCG) nano controlled-release preparation and preparation method thereof | |
| Wang et al. | Preparation of core-shell microcapsules based on microfluidic technology for the encapsulation, protection and controlled delivery of phycocyanin | |
| Chen et al. | Electrospun core–sheath nanofibers with a cellulose acetate coating for the synergistic release of zinc ion and drugs | |
| CN111407740A (en) | Albumin nanoparticles capable of activating and releasing drugs by ultrasound, and preparation method and application thereof | |
| Tulain et al. | Formulation and evaluation of Linum usitatissimum mucilage-based nanoparticles for effective delivery of ezetimibe | |
| Khan et al. | Recent advances in microbeads-based drug delivery system for achieving controlled drug release | |
| CN105820277B (en) | A kind of PBCA nanowire preparation method | |
| CN106389336B (en) | Liquid crystal nanoparticle precursor particles, self assembly liquid crystal nanoparticle and preparation method thereof | |
| CN114948880B (en) | Preparation method of caffeic acid phenethyl ester nano stable slow release formulation | |
| CN105663085B (en) | A kind of Paeonol nano controlled-release preparation and preparation method thereof | |
| Kenechukwu et al. | Novel Bos indicus fat-based nanoparticulate lipospheres of miconazole nitrate as enhanced mucoadhesive therapy for oral candidiasis | |
| Joshi et al. | Gelatin–rosin gum complex nanoparticles: preparation, characterization and colon targeted delivery of 5-fluorouracil | |
| CN101822839B (en) | Preparation of nanometer structure lipid carrier by using seal oil as liquid-phase substrate and application | |
| CN111450078A (en) | Electrostatic spinning nanoparticle-entrapped pharmaceutical preparation and application thereof | |
| RU2727360C1 (en) | Method of producing chitosan nanoparticles | |
| Khare et al. | Influence of rheology of dispersion media in the preparation of polymeric microspheres through emulsification method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |