CN105343884B - A kind of preparation method and applications of electricity reaction transdermal drug delivery system - Google Patents
A kind of preparation method and applications of electricity reaction transdermal drug delivery system Download PDFInfo
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Abstract
The present invention relates to the preparation method and applications of the electric reaction gel of carboxylic carbon nano-tube carrying medicament, drug transdermal infiltration rate can be effectively improved, the technical solution of solution is: (1) drug is dissolved using solvent appropriate, and freezing ball milling in carboxylic carbon nano-tube is added and prepares loaded article.(2) carbon nanotube and polyacrylic acid, polyvinyl alcohol etc. constitute gel-type vehicle, are prepared into gelling agent after loaded article is added.(3) gelling agent cutaneous penetration under the action of extra electric field.Preparation process of the invention is simple, and experiment condition is mild, easily operated；Carboxylic carbon nano-tube loads insoluble drug, water solubility enhancing；The release of drug has correlation with extra electric field, and the infiltration rate of drug can be improved, and has good practical value.
Description
Technical field
The present invention relates to field of medicine preparations, especially a kind of preparation method of electricity reaction transdermal drug delivery system, and its make
For application of the drug delivery carrier in local skin topical administration.
Background technique
Carbon nanotube (carbon nanotubes, CNTs) is a kind of particularly important inorganic nano-particle, including single wall carbon
Nanotube (SWCNTs) and multi-walled carbon nanotube (MWCNTs), cavity tube body can accommodate biologic specificity molecule and drug, and
It is carried into cell or tissue.Pharmaceutical activity molecule is carried on carbon nanotube in a manner of three kinds: first is that carbon nanotube as dredge
Loose absorbent absorption drug is in carbon pipe or carbon interfascicular；Second is that being formed by the carbon nanotube outer wall of functionalization with drug compound
Object；Third is that be wrapped in carbon nanotube intracavitary for drug.
Carbon nanotube does not dissolve in organic solvent and water, and can improve its dissolubility after functional modification, and its life can be improved
Object compatibility.CNTs method of modifying includes covalent modified and non-covalent modification.Covalent modified is enterprising in CNTs by chemical bond
The bonded modification of row group is such as acidified oxidation processes and 1,3- dipole open loop addition.Oxidation processes are acidified at the pipe end being truncated
And a small amount of fault location on tube wall, then the oxygen-containing groups such as a large amount of carboxyl can be introduced into, then recycle carboxyl to carry out subsequent
Modification such as uses a kind of polypeptide condensing agent EDC by carboxyl and small peptide, protein, anticancer drug (such as methotrexate) or targeting point
Amino on sub (such as folic acid) generates amide and is keyed on CNTs.Non-covalent modification is by non-covalent mode adhesion protein
Matter, DNA, anticancer drug (such as adriamycin), and these molecules are sent into cell interior.
Using carboxylic carbon nano-tube as carrier, insoluble drug is loaded, loaded article, medicine are prepared using the method for freezing ball milling
The water-soluble enhancing of object.It adds it in water-soluable gel matrix, or is prepared into emulsion and is added in water-soluable gel matrix, system
Standby at transdermal drug delivery system, the percutaneous rate of drug is improved, and the Percutaneous permeability of drug improves, and is conducive to drugs through skin and is played
Drug effect.Insoluble drug is not suitable for preparing water soluble gel, because insoluble drug is easy to be precipitated in water soluble gel
Solid, the solid state of drug is compared with liquid condition, it is difficult to transdermal cuticula.The present invention solves insoluble drug
Androgynous problem is precipitated in water soluble gel, solves the defect of existing preparation technique.
Suitable length, suitable carbon nanotube are added in common water-soluable gel matrix, it is good using carbon nanotube
Electric conductivity, and in the thermal sensitive effect of 808nm, improve the electric conductivity of gelling agent.Under extra electric field (electro-ionic osmosis), medicine
The percutaneous rate of object significantly improves, and is prepared into electric anti-with being positively correlated property of current density thus the percutaneous rate of regulating medicine
Answer transdermal drug delivery system.
Present invention employs carboxylic carbon nano-tube carrying medicaments to improve water solubility, is added using carbon nanotube water-soluble solidifying
Increase electric conductivity in gel matrix, under DC Electric Field, is prepared into electricity reaction transdermal drug delivery system.The drug that the present invention loads
Including Aceclofenac, hydroxycamptothecin, triptolide, cucoline, rutaecarpin, jamaicin, stephanine, piperine etc..
Preparation method of the invention is also applied for the drug or pharmaceutical composition of other cutaneous penetrations.The present invention is to utilize carboxylated carbon nanometer
The hollow structure carrying medicament of pipe is a kind of physics for improving transdermal delivery rates using the good electric conductivity of carbon nanotube
Method.The present invention can be used in combination with the chemical method or other physical methods for improving transdermal delivery rates.
About electricity reaction transdermal drug delivery system of the invention, have not been reported.
Summary of the invention
The primary purpose of the present invention is that providing a kind of preparation of the electric reaction gel of carboxylic carbon nano-tube carrying medicament
Method and its application can effectively improve the percutaneous rate of drug under DC Electric Field.
Another object of the present invention is to provide a kind of preparation methods of carboxylic carbon nano-tube carrying medicament, and its outside
With the application in preparation.
The purpose of the present invention is accomplished by the following way:
1, a kind of electricity reaction transdermal drug delivery system, it is characterised in that by carboxylic carbon nano-tube, carbon nanotube, drug structure
At；The carboxylic carbon nano-tube is carboxyl single-walled carbon nanotube and its derivative or carboxyl multi-walled carbon nanotube and its spreads out
Biology；The carbon nanotube is single-walled carbon nanotube or multi-walled carbon nanotube (1-500nm)；The drug be Aceclofenac,
Hydroxycamptothecin, triptolide, cucoline, rutaecarpin, jamaicin, stephanine, piperine etc..
2, the preparation method of electricity reaction transdermal drug delivery system, it is characterised in that (1) drug is dissolved using solvent appropriate, is added
Enter to freeze ball milling in carboxylic carbon nano-tube and prepares loaded article.(2) compositions such as carbon nanotube and Sodium Polyacrylate, polyvinyl alcohol are solidifying
Gel matrix is prepared into gelling agent after loaded article is added.(3) gelling agent cutaneous penetration under the action of extra electric field.
3, electricity reacts the preparation method of carboxylic carbon nano-tube in transdermal drug delivery system, and step is:
500mL 98%H is dispersed by commercially available carbon nanotube CNTs (500mg)2SO4And 65%HNO3Mix acid (3
: in 1, v/v), it is added in ball grinder, protection of liquid nitrogen, with 590 turns/min of revolving speed, ball milling 10-30min.With ultrapure water (18.2M
Ω) washing collects (0.45 μm of vinylidene chloride miillpore filter) after suction filtration to neutrality, and freeze-drying obtains carboxylic carbon nano-tube
(CNTs-COOH).Equipped in magnetic agitation rotor list neck round-bottom flask, above-mentioned CNTs-COOH (40mg) and dust technology is added
(2.6mol·L-1, 120mL), after being ultrasonically treated 10-30min, it is put into oil bath and loads onto spherical condensation tube and tail gas absorption pipe,
Heat cocurrent flow stirring for 24 hours.After reaction, cooling, it with milli-Q water to neutrality and collects, is freeze-dried, is purified
CNTs-COOH.Carboxylic carbon nano-tube is characterized using FIR, TGA, Raman spectrum.
4, electricity reacts the preparation method that drug in transdermal drug delivery system is carried on carboxylic carbon nano-tube (loaded article), step
Suddenly it is:
Precision weighs drug 1-100mg, and ultrasonic dissolution is prepared into drug solution in 10-100mL solvent, spare.It is accurate
The CNTs-COOH for weighing 50-500mg purifying is placed in ball grinder, divides 3-6 addition drug solution；Under protection of liquid nitrogen
590rpm·min-1Ball milling, each 10-30min.Mixture after ball milling is collected in tool plug brown triangular flask, 1- is stood
After for 24 hours, filtering removes unadsorbed medical fluid.Filter cake volatilizes, and 10-100mL pure water is added after organic solvent, be placed in centrifuge tube from
Heart 1-2h (12000rpmmin-1).Supernatant after centrifugation is freeze-dried to get loaded article.The characteristics of this loaded article
It is the drug for being insoluble in water, is prepared into water-soluble increase after loaded article.
The organic solvent of above-mentioned dissolution drug selects drug to be soluble in the double solvents therein more than one or both,
The maximum solvent of preferred agents solubility.Hydroxycamptothecin is preferably not limited to solvent methanol: methylene chloride (1: 1, v/v)；Vinegar
The fragrant acid of chlorine is preferably not limited to 95% ethyl alcohol of solvent；Triptolide, cucoline, rutaecarpin, jamaicin, stephanine, Hu
Green pepper alkali is preferably not limited to solvent methanol.
5, electricity reacts the preparation method of gel ointment in transdermal drug delivery system, and step is:
Bare substrate is by carbomer1g, Sodium Polyacrylate (NP-700) 5.5g, glycerol 20mL,
Sorbierite 2g, propylene glycol 4mL, azone 4mL, ethylenediamine tetra-acetic acid (EDTA) 0.01g, aluminum glycinate 0.275g, citric acid are
0.3g, deionized water 60mL (10cm × 20cm is made) composition.The compound matrix wherein formed with NP-700, carbomer；With
Aluminum glycinate is crosslinking agent, using citric acid as cross-linking regulator；Glycerol, sorbierite are moisturizer.
The preparation process flow of gel ointment: by 1g10 are sprinkling upon in deionized water 15mL, and low speed stirs
Mix 30min；Carboxylic carbon nano-tube loaded article 1-1000mg is weighed, after the dissolution of 5-10mL water is added, is added with stirring carbomer
In solution, A phase solution is obtained.
In B phase, 5.5g NP-700 is weighed, 20mL glycerol, propylene glycol 4mL, azone 4mL is added, grinds well；Add 10-
It is uniform to continue grinding for 500mg carbon nanotube.Sorbierite 2g, EDTA 0.01g 25mL deionized water dissolving, gradually grinding is added
Into B phase.
0.275g aluminum glycinate and 0.3g citric acid are dissolved in 15mL water, are C phase.C phase clear solution is added in stirring
Enter B phase, then A is added in the mixture of B, C phase.It is coated on 10cm × 20cm non-woven fabrics after grinding uniformly, room temperature decentralization
It sets overnight, compound with protective layer after dry, cutting packaging.
6, electricity reacts the preparation method of gelling agent in transdermal drug delivery system, it is characterised in that:
It weighs polyvinyl alcohol (PVA) in right amount, is dissolved in 80 DEG C of pure water, be prepared into 10% (W/V) solution, be cooled to room temperature.
Carboxylic carbon nano-tube loaded article 1-1000mg is weighed, after the dissolution of 5-10mL water is added, is added with stirring in PVA solution, obtains A
Phase solution.10-500mg carbon nanotube is added, grinding is uniform.
25% (W/V) glutaraldehyde solution, 10% sulfuric acid solution (V/V), 50% methanol (V/V), four kinds of 10% acetic acid (V/V)
Solution mixes according to 2: 1: 2: 3 ratios, obtains B phase solution.
In 10 parts of A phase solution, 1-3 parts of B phase solution are gradually added, is mixed evenly, is cast in the glass of 10cm × 20cm
In glass slot, drying and forming-film is compound with protective layer, cutting packaging.
7, the application of electricity reaction transdermal drug delivery system, it is characterised in that: be in extra electric field electro-ionic osmosis current density
0.20-0.60mA·cm-2When, the percutaneous rate of drug improves, and is positively correlated with current density.
8, drug percutaneous rate is characterized in that in electricity reaction transdermal drug delivery system: in impressed current or infrared light 808nm
Under the conditions of irradiation, or raising temperature, the percutaneous rate of drug is improved.
The present invention loads anti-tumor drug as transdermal drug delivery system, then is used for the various solid tumors of organ surface, including
There are breast cancer, carcinoma of penis, orchioncus, carcinoma of endometrium, choriocarcinoma, Primary Vaginal Carcinoma, Vulvar, skin
One of cancer, malignant mela noma.
Arbitrary external preparation dosage form can be made as transdermal drug delivery system in the present invention, such as: ointment, emulsion, patch
Agent, gelling agent etc..The additive of various preparations can be added in the present invention, such as: antioxidant, opacifier, penetrating agent, filler
Deng.
Physics of the present invention and chemical stability are good, and the condition of preparation readily satisfies, easy to use, and drug can be improved
Transdermal penetration rate meets clinical application requirement, has good practical value.
Detailed description of the invention
Fig. 1 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube
Fig. 2 is the Raman spectrogram of carboxylic carbon nano-tube
Fig. 3 is the hot weight curve of carboxylic carbon nano-tube
Fig. 4 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load Aceclofenac
Fig. 5 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load hydroxycamptothecin
Fig. 6 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load cucoline
Fig. 7 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load rutaecarpin
Fig. 8 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load jamaicin
Fig. 9 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load cepharanthine
Figure 10 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load piperine
Figure 11 is the Fourier infrared spectrum figure of carboxylic carbon nano-tube load triptolide
Specific embodiment
Embodiment 1: the preparation and characterization of carboxylic carbon nano-tube
500mL 98%H is dispersed by commercially available MWCNTs (500mg)2SO4And 65%HNO3Mix acid (3: 1, v/
V) it in, is added in ball grinder, protection of liquid nitrogen, with 590 turns/min of revolving speed, ball milling 20min.With ultrapure water (18.2M Ω) wash to
Neutrality collects (0.45 μm of vinylidene chloride miillpore filter) after suction filtration, after 60 DEG C of vacuum drying for 24 hours, obtains carboxylic carbon nano-tube
(MWCNTs-COOH)。
In the mono- neck round-bottom flask of 250mL equipped with magnetic agitation rotor, the MWCNTs-COOH of above-mentioned oxidation is added
(40mg) and dust technology (2.6molL-1, 120mL), be ultrasonically treated 30min after, be put into oil bath and load onto spherical condensation tube and
Tail gas absorption pipe is heated to reflux stirring for 24 hours.After reaction, cooling, it with milli-Q water to neutrality and collects, 60 DEG C of vacuum
It is dry for 24 hours after, the MWCNTs-COOH that is purified.Using FIR, TGA, Raman spectrum to modified multi-walled carbon nanotube into
Row characterization.
Fourier infrared spectrum characterization: as shown in Detailed description of the invention Fig. 1,3361cm-1There is broad peak in place, is the flexible vibration of O-H
It is dynamic；2956cm-1And 2884cm-1It is asymmetric stretching vibration and the symmetrical stretching vibration of C-H respectively；1714cm-1It is then C=O
Stretching vibration.It proves to introduce carboxyl in carbon nanotube.
Raman Characterization characterization: as shown in Detailed description of the invention Fig. 2,1328cm-1The D band and 1587cm at place-1The G band at place is all
In the presence of.After proving using ball-milling method to multi-walled carbon nanotube oxidation processes, and the intrinsic structure of carbon nanotube is had not been changed.
Thermogravimetric analysis: as shown in Detailed description of the invention Fig. 3, carboxylic carbon nano-tube 4.5mg carries out thermogravimetric analysis, and heating rate is
10 DEG C/min, nitrogen atmosphere, the results showed that between 50-600 DEG C, sample quality variation is smaller, is reduced to from 4.5mg
3.5mg.And there is inflection point when 600 DEG C of quality are 3.5mg, quality sharply declines；Between 600-700 DEG C, 2.75mg is had dropped
(being 0.7 at 700 DEG C), this calculates carboxylated degree according to front and back weight difference for the process that carbon nanotube side chain carboxyl group decomposes
Account for the 61.1% of sample quality.
Embodiment 2: the preparation of Aceclofenac (Aceclofenac is abbreviated as AC) electricity reaction transdermal drug delivery system
Precision weighs AC and 25mgmL is made-1The solution 30mL of (95% ethyl alcohol), it is spare.Weigh the MWCNTs- of 500mg
COOH is placed in ball grinder, is added three times medical fluid, 10mL is added every time；590rpmmin under protection of liquid nitrogen-1Ball milling 6min.It takes
Suspension and excessively 0.45 μm of miillpore filter out after filtering is washed with deionized in filter cake, are freeze-dried to get carboxylated multi wall carbon
Nano tube supported Aceclofenac answers loading (AC-MWCNTs-COOH).
The IR Characterization of AC-MWCNTs-COOH, (A, B, C are respectively Aceclofenac original in figure as shown in Detailed description of the invention Fig. 4
Expect the infared spectrum of medicine, loaded article AC-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), Aceclofenac raw material
Carboxyl peak 3317cm-1Locate, in 1715cm-1、1713cm-1After being prepared into loaded article, there is 3400cm in the spike at place-1、
1700cm-1The blunt peak at place；Carboxylic carbon nano-tube 1715cm-1Locate spike to disappear.Show that Aceclofenac has been carried on carboxylated
In carbon nanotube.
Aceclofenac electricity reacts the preparation method and step of gel ointment in transdermal drug delivery system: by 1g10 are sprinkling upon in deionized water 15mL, stir at low speed 30min；AC-MWCNTs-COOH 0.5g is weighed, is added
After the dissolution of 5mL water, it is added with stirring in carbomer solution, obtains A phase solution.In B phase, 5.5g NP-700 is weighed, 20mL is added
Glycerol, propylene glycol 4mL, azone 4mL, grind well；100mg carbon nanotube is added, it is uniform to continue grinding.Sorbierite 2g, EDTA
0.01g 25mL deionized water dissolving, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate is dissolved in 0.3g citric acid
It is C phase in 15mL water.B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding is uniform
After be coated on 10cm × 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, be cut into 6 × 8cm2Packet
Dress.
Embodiment 3: Aceclofenac electricity reacts the measurement of the percutaneous rate of transdermal drug delivery system
To compare, Aceclofenac electricity reacts transdermal drug delivery system (AC-MWCNTs-COOH gel ointment) and common vinegar chlorine is fragrant
The percutaneous rate of acid gel paste (AC gel ointment), prepares AC gel ointment first, and method and the process distinction of preparation are
AC is bulk pharmaceutical chemicals, unused carboxylic carbon nano-tube load；Carbon nanotube is not added in gel-type vehicle.
Concrete operation step: by 1g10 are sprinkling upon in deionized water 15mL, stir at low speed 30min；Claim
AC 0.5g is taken, after the dissolution of 95% ethyl alcohol of 5mL is added, is added with stirring in carbomer solution, obtains A phase solution.In B phase, claim
5.5g NP-700 is taken, 20mL glycerol, propylene glycol 4mL, azone 4mL is added, grinds well.Sorbierite 2g, EDTA 0.01g are gone with 25mL
Ionized water dissolution, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate and 0.3g citric acid are dissolved in 15mL water, are C phase.
B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding uniformly after be coated on 10cm ×
On 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, it is cut into 6 × 8cm2Packaging.
Dermal penetration rate is measured using Franze diffusion cell method, step: the previously prepared rat skin in vitro of F (back), respectively
Mouse skin, bag filter are lain in into reception tank upper end, inject receiving liquid 7mL in receiving chamber, keeps 32 ± 0.2 DEG C of waters bath with thermostatic control,
Magnetic agitation rotating speed is 200 ± 5rpm, pre-balance 1h.The solution in reception tank is outwelled, blank receiving liquid is added.In release pond
Pour into for examination gel 3mL (AC-MWCNTs-COOH gel ointment or AC gel ointment, concentration of the two containing AC are
0.1g·mL-1), the fresh receiving liquid of same volume is added after separately sampled 5mL of scheduled interval time, every sub-sampling side by side
Except the bubble in receiving chamber.Above-mentioned dissolution fluid 5mL is dried with nitrogen, methanol constant volume to 1mL, is crossed 0.22 μm of filter membrane, is taken 20 μ of subsequent filtrate
L, by chromatographic condition sample introduction.Unit of account area cumulative release amount (Q, μ gcm as follows-2)。
In formula, drug concentration (μ gmL that Cn: n-th sample point measures-1)；Ci: the i-th (i=n-1) a sample point measures
Drug concentration (μ gmL-1)；A: mouse surface product (2.92cm2).Curve done to t with Qn, and to the straight line portion in curve into
Row returns, and finds out straight slope, calculates steady-state permeation rate Js (the μ gcm of drug-2·h-1), find out lag time Ttag。
On the basis of above-mentioned Transdermal absorption experimental provision, NPD-4AS type therapeutic equipment for hyperosteogeny is accessed as outer power-up
?.AC contains carboxyl, negatively charged, therefore negative plate is contacted with the keratoderma that joined gel when testing, size with it is effective
Transdermal skin area equation.Anode is placed in receiving chamber bottom.Setting electric current density is respectively 0.50mAcm-2、0.30mA·cm-2、0.20mA·cm-2, start timing after energization 20min and receive sample.Percutaneous rate changes after investigating electro-ionic osmosis.
Experimental result (see shown in Figure of abstract) shows: AC gel ointment and AC-MWCNTs-COOH gel ointment are in 4-
Reach stable state for 24 hours, steady-state permeation rate is respectively 0.5807 and 1.8615 μ gcm-2·h-1, lag time TtagRespectively
1.53h and 1.94h.Two stages are presented in percutaneous rate after electro-ionic osmosis, and 1-4h is quick release, Js is respectively 3.7292,
6.2125、8.7219μg·cm-2·h-1, percutaneous rate is positively correlated with current density；6-24h is slow release, and Js is respectively
0.8348、0.7106、0.9999μg·cm-2·h-1, percutaneous rate reaches unanimity.The quick release of bag filter is 1-14h, is delayed
On The Drug Release is 16-24h, is greater than percutaneous rate in quick release stage rate of release, therefore belongs to skin speed limit type cutaneous penetration system
System.
1 dermal penetration rate of table (rate of release) and fit equation
Experimental result explanation: Aceclofenac is fat-soluble medicine, and solubility is smaller in water, is inhaled by carboxylic carbon nano-tube
Attached solubility increases.Therefore the percutaneous rate of AC-MWCNTs-COOH gel ointment is greater than AC gel ointment, it is seen that carboxylated carbon
Nanotube can improve percutaneous rate.But drug will desorption could be transdermal from carrier material, therefore AC-MWCNTs-COOH is solidifying
Glue paste extends compared with the transdermal time lag of AC gel ointment, extends to 1.94h from 1.53h.Under the action of extra electric field, because carbon is received
The electric action of mitron and quick release, percutaneous rate show with the increase of extra electric field and step up becoming for percutaneous rate
Gesture.
Embodiment 4: hydroxycamptothecin (10-hydroxy camptothecin, be abbreviated as HCPT) electricity reaction cutaneous penetration
The preparation of system
HCPT 4mg ultrasonic dissolution is weighed in 10mL methanol: it is molten to be prepared into drug for methylene chloride (1: 1) in the mixed solvent
Liquid, it is spare.The MWCNTs-COOH that precision weighs 50mg is placed in ball grinder, is added three times medical fluid, and about 3mL is added every time；Liquid
Nitrogen protects lower 590rpmmin-1Ball milling 10min.Mixture after ball milling is collected in tool plug brown triangular flask, is stood for 24 hours
Afterwards, it filters, removes unadsorbed medical fluid.Filter cake is put into culture dish, and 10mL pure water is added after organic solvent is volatilized, shakes up postposition
In in centrifuge tube from 1h (12000rpmmin-1).Supernatant after centrifugation is freeze-dried to get loaded article HCPT-
MWCNTs-COOH。
The IR Characterization of HCPT-MWCNTs-COOH, (A, B, C are respectively hydroxy-camptothecin in figure as shown in Detailed description of the invention Fig. 5
The infared spectrum of alkali bulk pharmaceutical chemicals, loaded article HCPT-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), loaded article is red
Apparent change has occurred in outer map, and HCTP is in 1500-1750cm-1Three spikes disappear, and in 1500-400cm-1Refer to
Line area also changes, and shows that hydroxycamptothecin has been carried in carboxylic carbon nano-tube.
Hydroxycamptothecin electricity reacts the preparation method of gelling agent in transdermal drug delivery system, it is characterised in that: weighs polyethylene
Alcohol (PVA) in right amount, is dissolved in 80 DEG C of pure water, is prepared into 10% (W/V) solution, is cooled to room temperature.Weigh recipe quantity carboxylated carbon
Nano tube supported object (320mg containing HCPT) is added with stirring in PVA solution after the dissolution of 5mL water is added, obtains A phase solution.Again
100mg carbon nanotube is added, grinding is uniform.25% (W/V) glutaraldehyde solution, 10% sulfuric acid solution (V/V), 50% methanol (V/
V), 10% acetic acid (V/V), four kinds of solution mix according to 2: 1: 2: 3 ratios, obtain B phase solution.In 10 parts of A phase solution, gradually plus
Enter 1 part of B phase solution, be mixed evenly, be cast in the glass guide channel of 10cm × 20cm, drying and forming-film is compound with protective layer, cuts
It is cut into 6 × 8cm2 packaging.
Embodiment 5: the preparation of cucoline (Sinomenine is abbreviated as S) electricity reaction transdermal drug delivery system
Precision weighs cucoline 50mg ultrasonic dissolution in 50mL methanol, is prepared into drug solution, spare.Weigh 500mg
MWCNTS-COOH's is placed in ball grinder, is added three times medical fluid, and about 15mL is added every time；590rpmmin under protection of liquid nitrogen-1
Ball milling 6min.Mixture after ball milling is collected in tool plug brown triangular flask and (is protected from light operation), stands 12h.It will be unadsorbed
Medical fluid is fallen with 0.45 μm of organic membrane filtration, and with 10mL methanol rinses filter cake；Filter cake is put into culture dish, and organic solvent is volatilized
30mL pure water is added afterwards, is lightly ground about 5min and is placed on centrifugation 1h (12000rpmmin-1) in centrifuge tube.After centrifugation
Supernatant is freeze-dried to get loaded article S-MWCNTs-COOH.
The IR Characterization of S-MWCNTs-COOH, (A, B, C are respectively cucoline raw material in figure as shown in Detailed description of the invention Fig. 6
The infared spectrum of medicine, loaded article S-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH).Carboxylic carbon nano-tube and
Cucoline is respectively in 3361cm-1And 3429cm-1The characteristic absorption peak of neighbouring appearance-OH；And in S-MWCNTs-COOH-OH suction
It receives peak and then appears in 3429cm-1Near, and width becomes larger；S-MWCNTs-COOH is in 1600cm-1, 1412cm-1, 1316cm-1,
1122cm-1Nearby there is new absorption peak, the characteristic absorption peak of-C=O and Ar-H in cucoline can be attributed to respectively, this
A degree of offset has occurred in the position at a little peaks, shows that cucoline has been carried in carboxylic carbon nano-tube.
Cucoline electricity reacts the preparation method and step of gel ointment in transdermal drug delivery system: will10
It is sprinkling upon in deionized water 15mL, stirs at low speed 30min；S-MWCNTs-COOH 0.5g is weighed, after the dissolution of 5mL water is added, stirring
In lower addition carbomer solution, A phase solution is obtained.In B phase, weigh 5.5g NP-700, be added 20mL glycerol, propylene glycol 4mL,
Azone 4mL, grinds well；Prescription 200mg carbon nanotube is added, it is uniform to continue grinding.Sorbierite 2g, EDTA 0.01g are gone with 25mL
Ionized water dissolution, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate and 0.3g citric acid are dissolved in 15mL water, are C phase.
B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding uniformly after be coated on 10cm ×
On 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, it is cut into 6 × 8cm2 packaging.
Embodiment 6: the preparation of rutaecarpin (Evodiamine is abbreviated as ED) electricity reaction transdermal drug delivery system
Precision weighs rutaecarpin bulk pharmaceutical chemicals 10mg ultrasonic dissolution in 20mL methanol, is prepared into drug solution, spare；Essence
It is close to weigh being placed in ball grinder of 100mg MWCNTS-COOH (carboxylic carbon nano-tube), it is added three times medical fluid, is added every time
About 6mL；580rpmmin under protection of liquid nitrogen-1Ball milling three times, each 10min；Mixture after ball milling is collected in tool plug brown
(operation is protected from light) in triangular flask, stands 12h；0.45 μm of organic membrane filtration of unadsorbed medical fluid is fallen, and is moistened with 5mL methanol
Filter wash cake；Filter cake is put into culture dish, and 10mL pure water is added after methanol is volatilized, is lightly ground about 5min；It is placed in centrifuge tube
It is centrifuged 1h (12000rpmmin-1)；Supernatant after centrifugation is freeze-dried for 24 hours to get ED-MWCNTs-COOH.
The IR Characterization of ED-MWCNTs-COOH, (A, B, C are respectively rutaecarpin original in figure as shown in Detailed description of the invention Fig. 7
Expect the infared spectrum of medicine, loaded article ED-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), in 3437cm-1Near
There is the characteristic absorption peak of-OH, belong to the characteristic peak of-OH in carboxylic carbon nano-tube, this peak is compared with carboxylic carbon nano-tube-
Certain offset has occurred in OH absorption peak.Illustrate, after carboxylic carbon nano-tube loads ED ,-OH group is received on drug molecule
The influence of group.ED-MWCNTs-COOH is in 1624cm-1Nearby there is new absorption peak, is attributed in rutaecarpin
1629cm-1The characteristic absorption peak of neighbouring C-O, and the strength reduction at peak；In 705cm-1The peak nearby occurred belongs to rutaecarpin
Middle 1503cm-1, 734cm-1The characteristic absorption peak of neighbouring phenyl ring.Show that rutaecarpin has been carried on carboxylic carbon nano-tube
It is interior.
Rutaecarpin electricity reacts the preparation method and step of gel ointment in transdermal drug delivery system: by 1g10 are sprinkling upon in deionized water 15mL, stir at low speed 30min；ED-MWCNTs-COOH 0.5g is weighed, is added
After the dissolution of 5mL water, it is added with stirring in carbomer solution, obtains A phase solution.In B phase, 5.5g NP-700 is weighed, 20mL is added
Glycerol, propylene glycol 4mL, azone 4mL, grind well；200mg carbon nanotube is added, it is uniform to continue grinding.Sorbierite 2g, EDTA
0.01g 25mL deionized water dissolving, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate is dissolved in 0.3g citric acid
It is C phase in 15mL water.B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding is uniform
After be coated on 10cm × 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, be cut into 6 × 8cm2Packet
Dress.
Embodiment 7: the preparation of jamaicin (Berberine is abbreviated as BB) electricity reaction transdermal drug delivery system
Precision weighs jamaicin bulk pharmaceutical chemicals 60mg ultrasonic dissolution in 20mL methanol, is prepared into drug solution, spare；It is accurate
Being placed in ball grinder for 200mgMWCNTS-COOH (carboxylic carbon nano-tube) is weighed, medical fluid is added three times, is added every time about
6mL；580rpmmin under protection of liquid nitrogen-1Ball milling three times, each 10min；Mixture after ball milling is collected in tool plug brown three
(operation is protected from light) in the bottle of angle, stands 12h；0.45 μm of organic membrane filtration of unadsorbed medical fluid is fallen, and with 5mL methanol rinses
Filter cake；Filter cake is put into culture dish, and 10mL pure water is added after methanol is volatilized, is lightly ground about 5min；Be placed in centrifuge tube from
Heart 1h (12000rpmmin-1)；Supernatant after centrifugation is freeze-dried for 24 hours to get BB-MWCNTs-COOH.
The IR Characterization of BB-MWCNTs-COOH, (A, B, C are respectively jamaicin raw material in figure as shown in Detailed description of the invention Fig. 8
The infared spectrum of medicine, loaded article BB-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), BB-MWCNTs-COOH's
Infared spectrum is in 3460cm-1Nearby there is the characteristic absorption peak of-OH, belong to the characteristic peak of-OH in carboxylic carbon nano-tube,
Certain offset has occurred compared with the absorption peak of-OH in carboxylic carbon nano-tube for the peak, and peak shape narrows, this explanation, carrier material
After expecting carrying medicament ,-OH group above receives the influence of group on drug molecule.The infrared figure of BB-MWCNTs-COOH exists
1627cm-1And 1384cm-1Nearby there is new absorption peak, is attributed to jamaicin bulk pharmaceutical chemicals 1634cm respectively-1And 1385cm-1Peak is born
It is displaced after load, while the 1714cm of carboxylic carbon nano-tube-1Carbonyl peak disappears.The change of the above peak shape and peak position, table
Bright jamaicin has been carried in carboxylic carbon nano-tube.
Jamaicin electricity reacts the preparation method and step of gel ointment in transdermal drug delivery system: by 1g10 are sprinkling upon in deionized water 15mL, stir at low speed 30min；ED-MWCNTs-COOH 3g is weighed, is added
After the dissolution of 5mL water, it is added with stirring in carbomer solution, obtains A phase solution.In B phase, 5.5g NP-700 is weighed, 20mL is added
Glycerol, propylene glycol 4mL, azone 4mL, grind well；200mg carbon nanotube is added, it is uniform to continue grinding.Sorbierite 2g, EDTA
0.01g 25mL deionized water dissolving, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate is dissolved in 0.3g citric acid
It is C phase in 15mL water.B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding is uniform
After be coated on 10cm × 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, be cut into 6 × 8cm2Packet
Dress.
Embodiment 8: the preparation of cepharanthine (Cepharanthine is abbreviated as CP) electricity reaction transdermal drug delivery system
Precision weighs cepharanthine bulk pharmaceutical chemicals 20mg ultrasonic dissolution in 20mL methanol, is prepared into drug solution, spare；Claim
Being placed in ball grinder for 100mg MWCNTS-COOH (carboxylic carbon nano-tube) is taken, medical fluid is added three times, is added every time about
6mL；580rpmmin under protection of liquid nitrogen-1Ball milling three times, each 10min；Mixture after ball milling is collected in tool plug brown three
(operation is protected from light) in the bottle of angle, stands 12h；0.45 μm of organic membrane filtration of unadsorbed medical fluid is fallen, and with 5mL methanol rinses
Filter cake；Filter cake is put into culture dish, and 10mL pure water is added after methanol is volatilized, is lightly ground about 5min；Be placed in centrifuge tube from
Heart 1h (12000rpmmin-1)；Supernatant after centrifugation is freeze-dried for 24 hours to get CP-MWCNTs-COOH.
The IR Characterization of CP-MWCNTs-COOH, (A, B, C are respectively cepharanthine original in figure as shown in Detailed description of the invention Fig. 9
Expect the infared spectrum of medicine, loaded article CP-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), in 3441cm-1Near
There is the characteristic absorption peak of-OH, be attributed to the characteristic peak of-OH in carboxylic carbon nano-tube, the peak is compared with-the OH in carrier material
Absorption peak certain offset has occurred, this explanation, after carrier material carrying medicament ,-OH group above receives drug point
The influence of group on son；In 1638cm-1Nearby there is an absorption peak, is attributed to cepharanthine in 1623cm-1Neighbouring phenyl ring
On skeleton C=C stretching vibration；2934cm-1、1384cm-1For the characteristic peak of raw material, do not change；Carboxylated carbon nanometer
The 1715cm of pipe-1Carbonyl peak disappears.Show that cepharanthine has been carried in carboxylic carbon nano-tube.
Cepharanthine electricity reacts the preparation method of gelling agent in transdermal drug delivery system, it is characterised in that: weighs polyvinyl alcohol
(PVA) in right amount, it is dissolved in 80 DEG C of pure water, is prepared into 10% (W/V) solution, is cooled to room temperature.Recipe quantity carboxylated carbon is weighed to receive
Mitron loaded article (20mg containing CP) is added with stirring in PVA solution after the dissolution of 10mL water is added, obtains A phase solution.It adds
100mg carbon nanotube, grinding are uniform.25% (W/V) glutaraldehyde solution, 10% sulfuric acid solution (V/V), 50% methanol (V/V),
10% acetic acid (V/V), four kinds of solution mix according to 2: 1: 2: 3 ratios, obtain B phase solution.In 10 parts of A phase solution, it is gradually added 3
Part B phase solution, is mixed evenly, is cast in the glass guide channel of 10cm × 20cm, and drying and forming-film is compound with protective layer, cutting
At 6 × 8cm2Packaging.
Embodiment 9: the preparation of piperine (Piperine is abbreviated as PP) electricity reaction transdermal drug delivery system
Precision weighs piperine bulk pharmaceutical chemicals 5mg ultrasonic dissolution in 10mL methanol, is prepared into drug solution, spare；It weighs
Being placed in ball grinder for 50mg MWCNTS-COOH (carboxylic carbon nano-tube), is added three times medical fluid, and about 3mL is added every time；Liquid
Nitrogen protects lower 580rpmmin-1Ball milling three times, each 6min；Mixture after ball milling is collected in tool plug brown triangular flask
(being protected from light operation) stands 12h；0.45 μm of organic membrane filtration of unadsorbed medical fluid is fallen, and with 2mL methanol rinses filter cake；
Filter cake is put into culture dish, and 10mL pure water is added after methanol is volatilized, is lightly ground about 5min；It is placed in centrifuge tube and is centrifuged 1h
(12000rpm·min-1)；Supernatant after centrifugation is freeze-dried for 24 hours to get loaded article PP-MWCNTs-COOH.
The IR Characterization of PP-MWCNTs-COOH, (A, B, C are respectively piperine raw material in figure as shown in Detailed description of the invention Figure 10
The infared spectrum of medicine, loaded article PP-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), in 3441cm-1Nearby go out
Show the characteristic absorption peak of-OH, is attributed to the characteristic peak of-OH in carboxylic carbon nano-tube, the peak is compared with-the OH's in carrier material
Certain offset has occurred in absorption peak；In 1634cm-1There is an absorption peak in vicinity, is attributed to piperine bulk pharmaceutical chemicals and exists
1633cm-1The stretching vibration of skeleton C=C on neighbouring phenyl ring；In 1448cm-1, 1384cm-1The absorption peak nearby occurred can be with
Piperine is attributed in 1474cm-1, 1366cm-1Neighbouring C-H in-plane bending vibration peak；The 1715cm of carboxylic carbon nano-tube-1Carbonyl
Base peak disappears.Illustrate that PP-MWCNTs-COOH is successfully prepared, shows that piperine has been carried in carboxylic carbon nano-tube.
Piperine electricity reacts the preparation method of gelling agent in transdermal drug delivery system, it is characterised in that: weighs polyvinyl alcohol
(PVA) in right amount, it is dissolved in 80 DEG C of pure water, is prepared into 10% (W/V) solution, is cooled to room temperature.Recipe quantity carboxylated carbon is weighed to receive
Mitron loaded article (5mg containing PPR) is added with stirring in PVA solution after the dissolution of 5mL water is added, obtains A phase solution.It adds
100mg carbon nanotube, grinding are uniform.25% (W/V) glutaraldehyde solution, 10% sulfuric acid solution (V/V), 50% methanol (V/V),
10% acetic acid (V/V), four kinds of solution mix according to 2: 1: 2: 3 ratios, obtain B phase solution.In 10 parts of A phase solution, it is gradually added 2
Part B phase solution, is mixed evenly, is cast in the glass guide channel of 10cm × 20cm, and drying and forming-film is compound with protective layer, cutting
At 6 × 8cm2Packaging.
Embodiment 10: the preparation of triptolide (Triptolide is abbreviated as TP) electricity reaction transdermal drug delivery system
Precision weighs triptolide 20mg, and ultrasonic dissolution is prepared into drug solution in 20mL methanol, spare.It weighs
Being placed in ball grinder for 100mg MWCNTS-COOH (carboxylic carbon nano-tube), is added three times medical fluid, and about 6mL is added every time；
590rpmmin under protection of liquid nitrogen-1Ball milling 20min.Mixture after ball milling is collected in tool plug brown triangular flask and (is protected from light behaviour
Make), it stands for 24 hours.0.45 μm of organic membrane filtration of unadsorbed medical fluid is fallen, and with 5mL methanol rinses filter cake；Filter cake is put into
10mL pure water is added in culture dish after volatilizing methanol, be placed in centrifuge tube and be centrifuged 1h (12000rpmmin-1).After being centrifuged
Supernatant be freeze-dried to get loaded article TP-MWCNTs-COOH.
The IR Characterization of TP-MWCNTs-COOH, (A, B, C are respectively triptolide in figure as shown in Detailed description of the invention Figure 11
The infared spectrum of bulk pharmaceutical chemicals, loaded article TP-MWCNTs-COOH, carboxylic carbon nano-tube MWCNTs-COOH), triptolide is former
Expect medicine in 1788cm-1There is characteristic peak at place, is the stretching vibration of C=O；MWCNTs-COOH is in 1725cm-1There is characteristic peak at wavelength,
For the stretching vibration of-COOH；TP-MWCNTs-COOH is in 1765cm-1And 1730cm-1There is each strong absworption peak at place, this is bimodal,
It is respectively belonging to the 1788cm of TP raw material-1Characteristic peak and MWCNTs-COOH are in 1725cm-1Characteristic peak；In 3361cm-1Nearby go out
Show the characteristic absorption peak of-OH, is attributed to the characteristic peak of-OH in carboxylic carbon nano-tube, the peak is compared with-the OH's in carrier material
Certain offset has occurred in absorption peak.Illustrate that triptolide has loaded in carboxylic carbon nano-tube.
Triptolide electricity reacts the preparation method and step of gel ointment in transdermal drug delivery system: by 1g10 are sprinkling upon in deionized water 15mL, stir at low speed 30min；S-MWCNTs-COOH 10mg is weighed, is added
After the dissolution of 5mL water, it is added with stirring in carbomer solution, obtains A phase solution.In B phase, 5.5g NP-700 is weighed, 20mL is added
Glycerol, propylene glycol 4mL, azone 4mL, grind well；100mg carbon nanotube is added, it is uniform to continue grinding.Sorbierite 2g, EDTA
0.01g 25mL deionized water dissolving, gradually grinding is added in B phase.0.275g Dihydroxyaluminium Aminoacetate is dissolved in 0.3g citric acid
It is C phase in 15mL water.B phase is added in C phase clear solution in stirring, then A is added in the mixture of B, C phase.Grinding is uniform
After be coated on 10cm × 20cm non-woven fabrics, stand overnight at room temperature, it is compound with protective layer after dry, be cut into 6 × 8cm2 packet
Dress.
Claims (7)
1. a kind of electricity reaction transdermal drug delivery system, it is characterised in that: be made of carboxylic carbon nano-tube, carbon nanotube, drug；
The carboxylic carbon nano-tube is carboxyl single-walled carbon nanotube or carboxyl multi-walled carbon nanotube；The carbon nanotube is single wall
The multi-walled carbon nanotube of carbon nanotube or 1-500nm；The drug is Aceclofenac, hydroxycamptothecin, triptolide, sinomenium acutum
Alkali, rutaecarpin, jamaicin, cepharanthine or piperine；The preparation method of the electricity reaction transdermal drug delivery system includes such as
Lower step: (1) drug is dissolved using solvent appropriate, and freezing ball milling in carboxylic carbon nano-tube is added and prepares loaded article；(2) will
Carbon nanotube is added to the gel-type vehicle containing Sodium Polyacrylate or polyvinyl alcohol, is prepared into gelling agent after loaded article is added；
(3) gelling agent cutaneous penetration under the action of extra electric field.
2. electricity reaction transdermal drug delivery system described in claim 1, it is characterised in that: the preparation of the carboxylic carbon nano-tube
Method includes the following steps:
Disperse commercially available carbon nanotube CNTs500mg in the 98%H of 500mL3: 1 volume ratio2SO4And 65%HNO3It is mixed
It closes in acid, is added in ball grinder, protection of liquid nitrogen, with 590 turns/min of revolving speed, ball milling 10-30min；With the ultrapure washing of 18.2M Ω
It washs to neutrality, is collected after being filtered with 0.45 μm of vinylidene chloride miillpore filter, be freeze-dried, obtain carboxylic carbon nano-tube CNTs-
COOH；
In single neck round-bottom flask equipped with magnetic agitation rotor, above-mentioned CNTs-COOH40mg and 2.6molL is added-1It is dilute
Nitric acid 120mL is put into oil bath and loads onto spherical condensation tube and tail gas absorption pipe after being ultrasonically treated 10-30min, be heated to reflux
Stirring is for 24 hours；After reaction, cooling, it with milli-Q water to neutrality and collects, is freeze-dried, the CNTs- purified
COOH；Carboxylic carbon nano-tube is characterized using Fourier infrared spectrum FIR, thermogravimetric analysis TGA, Raman spectrum.
3. electricity reaction transdermal drug delivery system described in claim 1, it is characterised in that: the preparation method of the loaded article includes such as
Lower step:
Precision weighs drug 1-100mg, and ultrasonic dissolution is prepared into drug solution in 10-100mL solvent, spare；Precision weighs
The CNTs-COOH of 50-500mg purifying is placed in ball grinder, divides 3-6 addition drug solution；590rpm ball milling under protection of liquid nitrogen,
Each 10-30min；Mixture after ball milling is collected in tool plug brown triangular flask, after standing 1-24h, filtering, removing is not inhaled
Attached medical fluid；10-100mL pure water is added after volatilizing organic solvent in filter cake, is placed in centrifuge tube and is centrifuged with the speed of 12000rpm
1-2h；Supernatant after centrifugation is freeze-dried to get loaded article；The characteristics of this loaded article is the drug for being insoluble in water,
Water solubility increases after being prepared into loaded article；
Above-mentioned drug is hydroxycamptothecin or Aceclofenac or triptolide, cucoline, rutaecarpin, jamaicin, a thousand pieces of gold
Rattan element, piperine, solvent used in hydroxycamptothecin are methanol: the mixed solvent of 1: 1 volume ratio of methylene chloride；Aceclofenac institute
Solvent is 95% ethyl alcohol；It is triptolide, cucoline, rutaecarpin, jamaicin, cepharanthine, molten used in piperine
Agent is methanol.
4. the electricity reaction transdermal drug delivery system that claim 1 is stated, it is characterised in that: the preparation method of the gel-type vehicle, packet
Include following steps:
Bare substrate byCarbomer 1g, NP-700 Sodium Polyacrylate 5.5g, the glycerol 20mL, mountain of Ultrez 10
Pears alcohol 2g, propylene glycol 4mL, azone 4mL, ethylenediamine tetra-acetic acid 0.01g, aluminum glycinate 0.275g, citric acid 0.3g, deionized water
60mL composition；Compound matrix is wherein formed with NP-700 and carbomer；It is crosslinking with citric acid using aluminum glycinate as crosslinking agent
Regulator；Using glycerol, sorbierite as moisturizer；
The preparation process flow of gelling agent: by 1gUltrez 10 is sprinkling upon in deionized water 15mL, is stirred at low speed
30min；Loaded article 1-1000mg is weighed, after the dissolution of 5-10mL water is added, is added with stirring in carbomer solution, obtains A and mix
Liquid；
In B phase, 5.5g NP-700 is weighed, 20mL glycerol, propylene glycol 4mL, azone 4mL is added, grinds well；Add 10-500mg
It is uniform to continue grinding for carbon nanotube；Sorbierite 2g, EDTA 0.01g 25mL deionized water dissolving, gradually grinding is added to B phase
In；
0.275g aluminum glycinate and 0.3g citric acid are dissolved in 15mL water, are C phase；B is added in C phase clear solution in stirring
Phase, then A is added in the mixture of B, C phase；It is coated on 10cm × 20cm non-woven fabrics after grinding uniformly, placed at room temperature
It is night, compound with protective layer after dry, cutting packaging.
5. electricity reaction transdermal drug delivery system described in claim 1, it is characterised in that: the preparation method of the gelling agent, including
Following steps:
It is appropriate to weigh PVAC polyvinylalcohol, is dissolved in 80 DEG C of pure water, is prepared into the solution of 10%W/V, is cooled to room temperature；Weigh carboxylic
Base carbon nano tube loaded article 1-1000mg is added with stirring in PVA solution after the dissolution of 5-10mL water is added, obtains A and mix
Liquid；10-500mg carbon nanotube is added, grinding is uniform；
The glutaraldehyde solution of 25%W/V, the sulfuric acid solution of 10%V/V, the methanol of 50%V/V, four kinds of acetic acid of 10%V/V it is molten
Liquid mixes according to 2: 1: 2: 3 ratios, obtains B phase solution；
In 10 parts of A phase solution, 1-3 parts of B phase solution are gradually added, is mixed evenly, is cast in the glass guide channel of 10cm × 20cm
Interior, drying and forming-film is compound with protective layer, cutting packaging.
6. electricity described in a kind of claim 1-5 any one reacts transdermal drug delivery system, it is characterised in that:
It is 0.20-0.60mAcm in extra electric field electro-ionic osmosis current density-2When, the percutaneous rate of drug improves, and with
Current density is positively correlated.
7. electricity reaction transdermal drug delivery system described in claim 1, it is characterised in that: shone in impressed current or infrared light 808nm
It penetrates, or under the conditions of raising temperature, the percutaneous rate of drug is improved.
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| Carbon nanotubes for transdermal drug delivery;Ismail Tuncer Degim等;《Journal of Microencapsulation》;20100806;第27卷(第8期);摘要、结论部分，表2，第671页右栏第1段,第672页右栏倒数第2-3段，第677页右栏最后1段，图10、13 |
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