CN109646422A - A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite - Google Patents
A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite Download PDFInfo
- Publication number
- CN109646422A CN109646422A CN201910047553.5A CN201910047553A CN109646422A CN 109646422 A CN109646422 A CN 109646422A CN 201910047553 A CN201910047553 A CN 201910047553A CN 109646422 A CN109646422 A CN 109646422A
- Authority
- CN
- China
- Prior art keywords
- montmorillonite
- polyacrylic resin
- medicine
- drug
- organic
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The preparation method for carrying the ophthalmic administration system of medicine montmorillonite is wrapped up the invention discloses a kind of polyacrylic resin, this method is that the modified montmorillonite used absorption drug of acid activation must carry medicine montmorillonite；Polyacrylic resin, drug are dissolved in organic solvent under the conditions of Ultrasonic Heating, adds and carries medicine montmorillonite, organic phase is made；Surfactant is dissolved in water, water phase is made；Organic phase is injected in water phase, by organic-aqueous mixture ultrasound, continue to stir after ultrasound volatile organic solvent to get.The administration nano-drug administration system partial size that the polyacrylic resin package of the method for the present invention preparation carries medicine montmorillonite is small, is nanoscale, and have higher Zeta potential, has better adhesiveness with mucomembranous surface, to be conducive to improve the absorption and utilization of drug.A large amount of toxic organic solvents are not used, and simple to operate.
Description
Technical field
The present invention relates to field of medicaments, and in particular to polyacrylic resin package carries the novel Drug Delivery Systems of medicine montmorillonite
Preparation method.
Background technique
Traditional eye drip liquid dosage form is convenient because preparing simple, cheap, carrying and medication, is easy to be accepted by patients,
Therefore in ophthalmic remedy dosage form about 90% market share is occupied.However due to the special construction and physiologic factor of eye, by
In terms of eye anatomy and physiology many restrictions (such as lacrimal secretion and circulation, nasolacrimal duct elimination, blood aqueous barrier,
Blood-ocular barrier, blood-retina barrier etc.), after eye drops instills eye, it is very of short duration that medical fluid is stranded in the time in tear film, because
This active drug amount for making it possible to reach eye inner tissue only has the 1%~5% of dosage, therefore bioavilability is very low (logical
Often < 5%).How to increase drug in ocular absorption is the significant challenge that the delivery system is faced at present.
Nanoparticle is a kind of solid colloid dispersion of size in 1~1000nm, generally by lipid, protein, natural
Or polymer (such as albumin, mosanom, the chitosan and polycaprolactone) composition of synthesis.Because its partial size is small, can mention
The solubility of high drug and have certain adhesion property, it is expected to by further increase its adhesion property improve local retention when
Between achieve the effect that further enhance drug absorption.
Summary of the invention
The purpose of the present invention is to provide a kind of polyacrylic resin wrap up carry medicine montmorillonite ophthalmic administration system and its
Preparation method.
The technical solution used in the present invention is:
A kind of preparation method of the administration nano-drug administration system of polyacrylic resin package load medicine montmorillonite, comprising the following steps:
1) the modified montmorillonite used absorption drug of acid activation, must carry medicine montmorillonite；
2) polyacrylic resin, drug are dissolved in organic solvent under the conditions of Ultrasonic Heating, it is de- adds load medicine illiteracy
Organic phase is made in stone；
3) surfactant is dissolved in water, water phase is made；
4) organic phase is injected in water phase under agitation, organic-aqueous mixture ultrasound continues to stir after ultrasonic
It mixes volatile organic solvent and wraps up the administration nano-drug administration system for carrying medicine montmorillonite to get polyacrylic resin.
Preferably, the drug is cationic drug.
Preferably, the cationic drug includes betaxolol hydrochloride.
Preferably, in step 1), acid concentration when montmorillonite acid activation is 4~7v/v%.
Preferably, in step 2), the weight ratio of drug and polyacrylic resin is 1:2~1:10；Polyacrylic resin with
The weight ratio for carrying medicine montmorillonite is 11~56:0.5~1.
Preferably, the polyacrylic resin is selected fromRL PO andRS PO type poly- third
Olefin(e) acid resin.
Most preferably, the polyacrylic resin is 5:95's by mass ratioRS PO andRL PO composition.
Preferably, in step 2), the organic solvent is selected from acetone, methanol, methylene chloride, ethyl alcohol, chloroform, acetonitrile
At least one of.
Preferably, in step 2), the temperature of the heating is 30~60 DEG C.
Preferably, in step 3), the concentration of surfactant is 0.5%-2%w/v in water phase.
Preferably, the surfactant is selected from PLURONICS F87, poloxamer 147, poloxamer188, tween, gathers
At least one of ethylene glycol 400, cetomacrogol 1000, polyvinyl alcohol.
Preferably, in step 4), when organic phase is injected water phase, the temperature of organic phase is 30~60 DEG C, organic phase injection
Speed to water phase is 4~6mL/min.
Preferably, in step 4), the volume ratio of organic phase and water phase is 1:2~5.
Preferably, in step 4), the ultrasonic time is 5~15min, and ultrasonic power is 60~70%.
The polyacrylic resin package of any of the above-described the method preparation carries the administration nano-drug administration system of medicine montmorillonite.
The beneficial effects of the present invention are:
The administration nano-drug administration system partial size that the polyacrylic resin package of the method for the present invention preparation carries medicine montmorillonite is small, is nanometer
Grade, and have higher Zeta potential, with mucomembranous surface have better adhesiveness, thus be conducive to improve drug absorption and
It utilizes.
The method of the present invention mainly takes water as a solvent, and a large amount of toxic organic solvents is not used, and simple to operate.
Detailed description of the invention
Fig. 1 is the transmission electron microscope (TEM) that polyacrylic resin package prepared by embodiment 1 carries medicine montmorillonite nano suspension
Photo；
Fig. 2 is the particles size and distribution that polyacrylic resin package prepared by embodiment 1 carries medicine montmorillonite nano suspension
Figure；
Fig. 3 is different quality ratioRS PO andThe load medicine montmorillonite of RL PO preparation is received
Rice suspension In-vitro release curves, the RS in figure are indicatedRS PO, RL expressionRL PO；
Fig. 4 is the body that BH aqueous solution and polyacrylic resin package carry medicine montmorillonite nano suspension (Mt-BH NPs)
Outer release profiles；
Fig. 5 is blank intestinal mucosa solution (Mucin), blank nanoparticle suspension (Blank-NPs), polyacrylic resin load
Medicine montmorillonite nano grain suspension (Mt-BH-NPs), is added the intestinal mucosa (Blank-NPs+Mucin) that blank nanoparticle is added
Polyacrylic resin carries the Zeta potential of the intestinal mucosa (Mt-BH-NPs+Mucin) of medicine montmorillonite nano grain；
Fig. 6 is the Zeta potential that blank nanoparticle suspension and polyacrylic resin carry medicine montmorillonite nano grain suspension
Value；A is blank nanoparticle suspension, and B is that polyacrylic resin carries medicine montmorillonite nano grain suspension；A (a) and A (b) indicates empty
The current potential of white nanoparticle is the Performances of Novel Nano-Porous grain of rice (the polyacrylic resin load medicine that 21.39mV, B (a) and B (b) indicate the application preparation
Montmorillonite nano grain suspension) current potential up to 26.00mV.
Specific embodiment
The present invention is further illustrated combined with specific embodiments below.
Embodiment 1
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, is centrifuged, dry, and montmorillonite-betaxolol hydrochloride compound is made and (carries
Medicine montmorillonite)；
(2) precision weighs 425.6mgRL PO, 22.4mgRS PO, 56mg BH in
In test tube, 5mL dehydrated alcohol is added, 5mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Organic phase is made in compound；
Separately taking 1% PLURONICS F87 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), then by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, it removes
It is (i.e. poly- to obtain the polyacrylic resin package load medicine montmorillonite nano suspension with light blue opalescence for remaining organic solvent
Acrylic resin package carries the administration nano-drug administration system of medicine montmorillonite).
It is 78.53nm (see Fig. 1 that above-mentioned obtained polyacrylic resin package, which carries the average grain diameter of medicine montmorillonite nano grain,
And Fig. 2)；Average encapsulation rate is 75.63% (n=3)；Drugloading rate is (7.9783 ± 0.3363) %.Polyacrylic resin package
The release in vitro of medicine montmorillonite nano grain (Mt-BH NPs) is carried up to 10h or more, Accumulation dissolution is up to 78.33%, and the water of BH
Solution is just already basic in 2h to be discharged completely (see Fig. 4).
Embodiment 2
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 425.6mgRL PO,22.4mgRS PO, 56mgBH is in examination
Guan Zhong, is added 5mL acetone, and it is compound that 5mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Organic phase is made in object；
(3) separately taking 1% PLURONICS F87 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, is removed
Remaining organic solvent obtains the polyacrylic resin package with milky opalescence and carries medicine montmorillonite nano suspension.
Embodiment 3
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 425.6mgRL PO,22.4mgRS PO, 56mgBH is in examination
Guan Zhong, is added 5mL methylene chloride, and it is multiple that 5mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Object is closed, organic phase is made；
Separately taking 1% PLURONICS F87 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, is removed
Remaining organic solvent obtains the polyacrylic resin package with milky opalescence and carries medicine montmorillonite nano suspension.
Embodiment 4
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 425.6mgRS PO,22.4mgRL PO, 56mg BH in
In test tube, 5mL dehydrated alcohol is added, 5mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Organic phase is made in compound；
(3) separately taking 2% poloxamer188 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, is removed
Remaining organic solvent obtains the polyacrylic resin package with blue-opalescent and carries medicine montmorillonite nano suspension.
Embodiment 5
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 425.6mgRS PO,22.4mgRL PO, 56mg BH in
In test tube, it is added 5mL dehydrated alcohol, his Lip river of 10mg montmorillonite-hydrochloric acid times is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
That compound, is made organic phase；
Separately taking 1% polyethylene glycol 400 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, is removed
Remaining organic solvent obtains the polyacrylic resin package with blue-opalescent and carries medicine montmorillonite nano suspension.
Embodiment 6
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 224mgRS PO,224mgRL PO, 56mg BH are in test tube
In, 10mL dehydrated alcohol is added, it is multiple that 10mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Object is closed, organic phase is made；
Separately taking 1% cetomacrogol 1000 solution is water phase；
(4) 5mL organic phase is injected into 20mL water phase (note under 800rpm stirring condition by the organic phase that temperature is 50 DEG C
Entering speed is 5mL/min), by organic-aqueous mixture ultrasound 10min (power 65%), 2h is stirred after ultrasonic, is removed
Remaining organic solvent obtains the polyacrylic resin package with blue-opalescent and carries medicine montmorillonite nano suspension.
Embodiment 7
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 532mgRS PO,28mgRL PO, 56mg BH are in test tube
In, 10mL dehydrated alcohol is added, it is multiple that 10mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 30 DEG C of ultrasonic dissolutions
Object is closed, organic phase is made；
Separately taking 0.5% Tween 80 solution is water phase；
(4) organic phase that temperature is 30 DEG C is injected 10mL organic phase in 20mL water phase under 800rpm stirring condition
(injection rate 5mL/min) stirs 2h after ultrasonic, goes by organic-aqueous mixture ultrasound 10min (power 65%)
Except remaining organic solvent, obtains the polyacrylic resin package with blue-opalescent and carry medicine montmorillonite nano suspension.
Embodiment 8
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 90mgRS PO,22.4mgRL PO, 56mg BH are in test tube
In, 5mL dehydrated alcohol is added, it is multiple that 10mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Object is closed, organic phase is made；
(3) separately taking 1% PLURONICS F87 solution is water phase；
(4) organic phase that temperature is 50 DEG C is injected 5mL organic phase in 20mL water phase under 1000rpm stirring condition
(injection rate 5mL/min) stirs 2h after ultrasonic, goes by organic-aqueous mixture ultrasound 10min (power 65%)
Except remaining organic solvent, obtains the polyacrylic resin package with light blue opalescence and carry medicine montmorillonite nano suspension, mistake
Slightly precipitating generates after night places.
Embodiment 9
(1) montmorillonite is placed in the sulfuric acid of 5v/v%, 70 DEG C of water-baths are acidified 0.5h, are washed with distilled water to neutrality, surpass
Sonication obtains acidifying montmorillonite after dry, i.e., through the modified montmorillonite used of acid activation to reduce partial size；
Betaxolol hydrochloride (BH) aqueous solution that concentration is 3g/L is prepared, 1/3 acidification that weight is BH weight is added and covers
De- stone adjusts pH to 4, adsorbs 6h in 50 DEG C of water-baths, and after dry after centrifugation, montmorillonite-betaxolol hydrochloride compound is made (i.e.
Carry medicine montmorillonite)；
(2) precision weighs 358.4mgRS PO,89.6mgRL PO, 56mg BH in
In test tube, 5mL acetonitrile is added, it is multiple that 10mg montmorillonite-betaxolol hydrochloride is added after it is completely dissolved in 50 DEG C of ultrasonic dissolutions
Object is closed, organic phase is made；
(3) separately taking 1% poly-vinyl alcohol solution is water phase；
(4) organic phase that temperature is 50 DEG C is injected 5mL organic phase in 25mL water phase under 1000rpm stirring condition
(injection rate 5mL/min) stirs 2h after ultrasonic, goes by organic-aqueous mixture ultrasound 10min (power 65%)
Except remaining organic solvent, obtains the polyacrylic resin package with blue-opalescent and carry medicine montmorillonite nano suspension, it is overnight
Slightly precipitating generates after placement.
10 different proportion of embodimentRS PO andShadow of the RL PO to drug release
It rings method: different proportion is prepared according to 1 method of embodimentRS PO andRL PO mixing gathers
Acrylic resin package carries medicine montmorillonite nano suspension；WhereinRS PO andRL PO's
Mass ratio is set to 0:100,5:95,20:80,40:60,50:50,60:40,80:20,95:5,100:0.Using external saturating
Which kind of ratio is analysis bag method studyRS PO、RL PO polypropylene acid resin package carries
The release behavior of medicine montmorillonite nano suspension is more excellent.Firstly, pipetting 4mL carries medicine suspension in bag filter, by its both ends
It tightens and determines its no leakage, be placed in and fill 100mL dissolution medium (by 6.78g NaCl, 2.18g NaHCO3、0.084g
CaCl2·H2O and 1.38g KCl is placed in 1000mL deionized water, is sufficiently stirred and is uniformly mixed so as to obtain dissolution medium) wide-mouth bottle in,
Wide-mouth bottle is placed in 34 ± 1 DEG C, the gas bath constant temperature oscillator of 120rpm revolving speed.5mL release is drawn in specific time interval
Medium, while the fresh dissolution medium of same volume is added, keep the dissolution medium constant volume in wide-mouth bottle.Using it is ultraviolet can
See spectrophotometer, absorbance is measured at 273nm wavelength.
As a result: the polyacrylic resin package of different proportion carries the In-vitro release curves result of medicine montmorillonite nano grain as schemed
Shown in 3, as seen from the figure, arbitrary proportionRS PO andThe polyacrylic resin of RL PO preparation
Package carries medicine montmorillonite nano grain and all has good slow release effect, and total drug that each group is sustained after sustained release 50h is less than 90%.Especially
It is whereinRS PO andRL PO mass ratio is that the nanoparticle that 5:95 is prepared has most preferably
Slow release effect.Since the quaternary amine salt content of polyacrylic resin is different, cause lower containing quaternary ammonium saltRS
PO permeability and swellability are smaller, and salt groups containing quaternary amine are higherRL PO is then relatively high, and the two is mutual
It is used cooperatively, the drug release behavior of adjustable preparation.
11 polyacrylic resin of embodiment carries the mucoadhesive test of medicine montmorillonite nano drug delivery system
Method: (1) rat is put to death using disconnected cervical approach, takes out small intestine after operating scissors abdominal cut, is made with normal saline flushing
Content is peace and quiet, scrapes intestinal mucosa in 10mL centrifuge tube.The intestinal mucosa of equivalent is taken to be suspended respectively with the blank nanoparticle of equivalent
The polyacrylic acid tree of liquid (preparation method is same as Example 1, but without montmorillonite and drug BH) and preparation of the embodiment of the present invention
Rouge carries vortex 1min and ultrasound mixing after the mixing of medicine montmorillonite nano grain suspension.Utilize Zeta potential and laser particle size analyzer
(Delsa Nano C particle Size and Zeta Potential Analyzer；BeckmanCoulter,Brea,
CA, USA) measurement blank intestinal mucosa solution (Mucin), blank nanoparticle suspension (Blank-NPs), polyacrylic resin load medicine
Montmorillonite nano grain suspension (Mt-BH-NPs), intestinal mucosa and blank nanoparticle suspension (Blank-NPs+Mucin), intestines are glutinous
Film and polyacrylic resin carry the Zeta potential of medicine montmorillonite nano grain suspension (Mt-BH-NPs+Mucin), according to Zeta electricity
Position changes the adhesiveness to judge nanoparticle.
As a result: mucoadhesive test result is as shown in Figure 5 and Figure 6.Its Zeta potential value of blank intestinal mucosa solution be-
13.81 ± 1.99mV, it is negatively charged, electrification property with it is expected consistent；Polyacrylic resin carries medicine montmorillonite nano grain and sky
White nanoparticle is compared, and the current potential of polyacrylic resin drug-carrying nanometer particle increased, such as A (a) in Fig. 6 and A (b), B
(a) and shown in B (b), the current potential of blank nanoparticle is 21.39mV, and (polyacrylic resin carries the Performances of Novel Nano-Porous grain of rice of the application preparation
Medicine montmorillonite nano grain suspension) current potential up to 26.00mV.(polyacrylic resin carries the Performances of Novel Nano-Porous grain of rice prepared by the present invention
Medicine montmorillonite nano grain suspension) show higher Zeta potential, thus be expected with before cornea in tear film it is negatively charged
Stronger more longlasting interaction occurs for mucin, more have this Nano grade of nanoparticle small size particle and high specific surface
The adhesion characteristics to mucomembranous surface that product has itself, work along both lines, and are conducive to raising drug and are absorbed and used.
In conclusion the present invention, which successfully prepares positively charged polyacrylic resin, carries medicine montmorillonite nano administration system
System, secondly because nanoparticle has the grain of some natural excellent properties such as its small Nano grade in this drug delivery system
Diameter, can inherently embody the increase of the specific surface area relative to the block materials order of magnitude, to be transmitted to nanoparticle spy
The superiority of mucomembranous surface (for example at eye cornea) physical adherence characteristic is presented in some, and Zeta potential test shows
Administration nano-drug administration system surface of the present invention shows electropositive, is 26.54 ± 2.05mV, enables it to and i.e. cornea on medicine-feeding part
Physical absorption and specificity occur for mucin negatively charged as caused by the goblet cell of conjunctiva on surface and tear film interface
Adhesion, mainly by the combination of the modes such as electrostatic attraction, hydrogen bond, hydrophobic bond so as in wider and more levels
The Performances of Novel Nano-Porous grain of rice is set to contact, adsorb, adhere to and persistently play a role with administration site of action, for the clinic hardly possible for solving ophthalmic administration
Topic provides a solution.Drug delivery system of the present invention can not only extend drug in the residence time of medicine-feeding part, additionally it is possible to
The stability for improving drug, promotes the absorption of drug, the very advantageous in terms of the local diseases such as treatment eye.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. the preparation method that a kind of polyacrylic resin package carries the administration nano-drug administration system of medicine montmorillonite, which is characterized in that including
Following steps:
1) the modified montmorillonite used absorption drug of acid activation, must carry medicine montmorillonite；
2) polyacrylic resin, drug are dissolved in organic solvent under the conditions of Ultrasonic Heating, add and carries medicine montmorillonite, system
Obtain organic phase；
3) surfactant is dissolved in water, water phase is made；
4) organic phase is injected in water phase under agitation, by organic-aqueous mixture ultrasound, continues stirring after ultrasonic and wave
It sends out organic solvent and wraps up the administration nano-drug administration system for carrying medicine montmorillonite to get polyacrylic resin.
2. the method according to claim 1, wherein the drug is cationic drug.
3. according to the method described in claim 2, it is characterized in that, the cationic drug includes betaxolol hydrochloride.
4. the method according to claim 1, wherein in step 2), the weight ratio of drug and polyacrylic resin
For 1:2~1:10；Polyacrylic resin and the weight ratio for carrying medicine montmorillonite are 11~56:0.5~1.
5. the method according to claim 1, wherein the polyacrylic resin is selected fromRL PO
WithRS PO type polyacrylic resin.
6. the method according to claim 1, wherein in step 2), the organic solvent be selected from acetone, methanol,
At least one of methylene chloride, ethyl alcohol, chloroform, acetonitrile.
7. the method according to claim 1, wherein the temperature of the heating is 30~60 DEG C in step 2)；Step
It is rapid 4) in, the ultrasonic time be 5~15min, ultrasonic power be 60~70%.
8. the method according to claim 1, wherein the concentration of surfactant is in water phase in step 3)
0.5%-2%w/v；The surfactant is selected from PLURONICS F87, poloxamer 147, poloxamer188, tween, poly- second
At least one of glycol 400, cetomacrogol 1000, polyvinyl alcohol.
9. the method according to claim 1, wherein in step 4), when organic phase is injected water phase, organic phase
Temperature is 30~60 DEG C, and the speed that organic phase is injected into water phase is 4~6mL/min；In step 4), the volume of organic phase and water phase
Ratio is 1:2~5.
10. system is administered in the nanometer that the polyacrylic resin package of any one of claim 1~9 the method preparation carries medicine montmorillonite
System.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910047553.5A CN109646422A (en) | 2019-01-18 | 2019-01-18 | A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910047553.5A CN109646422A (en) | 2019-01-18 | 2019-01-18 | A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109646422A true CN109646422A (en) | 2019-04-19 |
Family
ID=66120085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910047553.5A Pending CN109646422A (en) | 2019-01-18 | 2019-01-18 | A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109646422A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112451478A (en) * | 2020-11-26 | 2021-03-09 | 江苏远恒药业有限公司 | Timolol maleate eye drops and preparation process thereof |
| CN114344241A (en) * | 2021-12-15 | 2022-04-15 | 悦康药业集团安徽天然制药有限公司 | Polyacrylic resin modified adsorption drug carrier and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0451082A1 (en) * | 1990-04-03 | 1991-10-09 | Laboratorios Cusi, S.A. | Ophthalmic product |
| CN102309454A (en) * | 2010-07-02 | 2012-01-11 | 河南省眼科研究所 | Preparation method of econazole nitrate/polyacrylic resin cationic nanoparticles |
| CN103735518A (en) * | 2013-12-17 | 2014-04-23 | 广东药学院 | Preparation method of timolol maleate sustained release microspheres |
| CN104491867A (en) * | 2014-11-27 | 2015-04-08 | 广东药学院 | Preparation method of novel administration system with medicine-carrying montmorillonite wrapped by chitosan |
-
2019
- 2019-01-18 CN CN201910047553.5A patent/CN109646422A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0451082A1 (en) * | 1990-04-03 | 1991-10-09 | Laboratorios Cusi, S.A. | Ophthalmic product |
| CN102309454A (en) * | 2010-07-02 | 2012-01-11 | 河南省眼科研究所 | Preparation method of econazole nitrate/polyacrylic resin cationic nanoparticles |
| CN103735518A (en) * | 2013-12-17 | 2014-04-23 | 广东药学院 | Preparation method of timolol maleate sustained release microspheres |
| CN104491867A (en) * | 2014-11-27 | 2015-04-08 | 广东药学院 | Preparation method of novel administration system with medicine-carrying montmorillonite wrapped by chitosan |
Non-Patent Citations (3)
| Title |
|---|
| R.PIGNATELLO,ET AL.,: "Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application", 《BIOMATERIALS》 * |
| 李娟: "蒙脱石-聚丙烯酸树脂为载体的", 《工程科技Ⅰ辑》 * |
| 田双艳: "基于提高角膜前滞留的离子交换眼用纳米混悬剂的研究", 《工程科技Ⅰ辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112451478A (en) * | 2020-11-26 | 2021-03-09 | 江苏远恒药业有限公司 | Timolol maleate eye drops and preparation process thereof |
| CN114344241A (en) * | 2021-12-15 | 2022-04-15 | 悦康药业集团安徽天然制药有限公司 | Polyacrylic resin modified adsorption drug carrier and preparation method thereof |
| CN114344241B (en) * | 2021-12-15 | 2024-01-30 | 悦康药业集团安徽天然制药有限公司 | Polyacrylic resin modified adsorption drug carrier and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110664757B (en) | Nanocrystalline eye drop, preparation method and application thereof | |
| EP0975367B1 (en) | Improved delivery of drugs to mucosal surfaces | |
| KR101890503B1 (en) | Membrane-adherent self-assembled systems for treatment of ocular disorders | |
| CN104530256B (en) | Hyaluronic acid-vitamin E succinate polymer as well as preparation and application thereof | |
| IL99290A (en) | Liquid pharmaceutical compositions comprising a nonaqueous fluorinated liquid carrier and at least one polymeric drug delivery vehicle | |
| Jiang et al. | PLGA nanoparticle platform for trans-ocular barrier to enhance drug delivery: a comparative study based on the application of oligosaccharides in the outer membrane of carriers | |
| CN108578356B (en) | Artemether oral microemulsion in-situ gel and preparation method thereof | |
| CN104491867B (en) | A kind of preparation method of the novel Drug Delivery Systems of chitosan package load medicine montmorillonite | |
| CN109646422A (en) | A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite | |
| CN107320716A (en) | Basic fibroblast growth factor vesica and preparation method thereof | |
| CN104622847B (en) | A kind of microcapsule embedded multivesicular liposome pharmaceutical carrier and preparation method thereof | |
| Katiyar et al. | Microemulsions: A novel drug carrier system | |
| WO2021174894A1 (en) | Nanobowl-supported drug-loaded liposome, preparation method therefor, and application thereof | |
| CN105943500B (en) | A kind of antimycotic solution of ophthalmically acceptable nano-micelle containing Chinese mugwort Saperconazole | |
| CN102379850A (en) | Targeted administration liposome passing through mucus barriers of human bodies | |
| CN111494305A (en) | Lutein liposome ophthalmic temperature-sensitive in-situ gel preparation and preparation method thereof | |
| CN108309930B (en) | Ofloxacin liquid crystal gel nanoparticle eye drops and preparation method thereof | |
| CN106560175A (en) | Menthol-camphor eutectic mixture nano-emulsion in situ gel preparation | |
| JP2023041861A (en) | Formulation of nanostructured gels for increased agent loading and adhesion | |
| CN102028655B (en) | Zanamivir solid lipid nanosphere oral preparation and preparation method thereof | |
| CN106714803B (en) | Ophthalmic suspension formulations | |
| CN109718202B (en) | Targeting drug-loaded micelle suitable for carrying hydrophobic chemical drug | |
| Trivedi et al. | Effect of lipid composition on liposomal formulation of pramipexole | |
| CN115501203B (en) | Nanometer medicine carrier loaded with active ingredients and preparation method and application thereof | |
| CN109157511A (en) | Anti- new vessels class eye-drops preparations of a kind of ocular instillation and preparation method thereof |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190419 |
|
| RJ01 | Rejection of invention patent application after publication |