CN1663560A - Transdermal drug administering system - Google Patents
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Abstract
The invention discloses a percutaneous give drug system, which comprises: a drug storeroom, the gel drug layer comprises drug, solvent, transdermal accelerating agent and gelatinizing agent; one adsorption layer comprised solvent absorption material of solvent in absorbable drug storeroom; one isolating layer between drug storeroom and adsorption layer, which is of non-woven fabrics or semipermeable membrane to make solvent of gas or liquid pass through successfully; adsorption layer can joint isolating layer of drug storeroom in opposite directions of closing up to skin of drug storeroom. The percutaneous give drug system in this invention can increase drug level in drug storeroom of the system to elevate drug transdermal speed, as well as increase controlled release effect of percutaneous give drug and absolute bioavailability, enhance drug curative effect, decrease drug waste, and depress preparation cost of the system. The invention is fit particular to percutaneous give drug system for water-soluble drug of propranolol hydrochloride, verapamil hydrochloride and chlorpromazine hydrochloride.
Description
Technical field
The present invention relates to a kind of formulation method of field of medicaments, specifically a kind of transdermal delivery system.
Background technology
Transdermal delivery system is exactly in the mode of applying ointment or plaster on skin, and medicine sees through skin and enters blood circulation and reach effective blood drug concentration, realizes the novel drug-supplying system of a class of disease treatment or prevention.Its outstanding feature is exactly to avoid the first pass effect of hepar and the gastrointestinal tract deactivation of oral administration, can also keep constant blood drug level, improve curative effect and reduce toxic and side effects, the compliance and the safety that increase patient's medication reduce interindividual variation of patient's medication or the like.Just because of the outstanding advantage of percutaneous dosing, since first transdermal patch Scopolamine Patch listing of the U.S. in 1981, existing so far nine kinds of medicine dozens of kinds listing.
The main theoretical basis that supports transdermal delivery system is Fick (Ficks) diffusion law.The Ficks law is applied to the kinetics of diffusion of medicine in skin, can be reduced to following formula:
J＝PΔC (1)
J is the stable state percutaneous rate of medicine; P is an infiltration coefficient; Δ C represents that then the drug level of skin both sides is poor.It is generally acknowledged that medicine enters the body circulation by very fast the absorption by blood capillary of skin, promptly meets so-called " sink conditions ".Then (1) formula can be reduced to:
J＝PC
0 (2)
C
0Drug level for skin surface.From (2) formula as can be seen, the percutaneous rate of medicine is directly proportional with the drug level of skin surface.According to Fick's law, dissolved drug is to dermal osmosis, be diffused in the body by the direction of Concentraton gradient, thus the blood circulation of entering.
The difficulty of percutaneous dosing is the barrier action of skin to medicine, makes that medicine is difficult to see through the needs of skin with the effective blood drug concentration that satisfied therapeutical effect with fast speeds.Therefore, the key of transdermal administration technology is exactly to impel medicine to overcome the barrier action of skin, thereby makes medicine reach certain transmission speed.So for a long time, people study the whole bag of tricks such as chemical method (adding penetrating agent), iontophoresis, electroporation, supercritical ultrasonics technology or the like, increase the infiltration rate of medicine by this with the permeability that changes skin, also have by modification, wait as the profit partition coefficient that changes medicine to change the transparent performance of medicine skin to medicine itself.As the patent No. is base compositions and the medicament composition thereof that 93116890.2 patent of invention description discloses a kind of percutaneous dosing, this base adopts lower alcohol, wetting agent, water, stimulation depressant and absorption enhancer to constitute compositions, contain medicine in the compositions, then pass through to percutaneous drug delivery, medicine more effectively is absorbed, simultaneously, reduction is to the zest of medicine-feeding part.
On the other hand, according to Fick's law, the seepage velocity of medicine is directly proportional with the concentration difference of medicine in the skin both sides, therefore adopts the drug level that increases transdermal delivery system to improve the penetrating speed of medicine.Yet, increase drug level and be subjected to the restriction of the solubility property of medicine own and the Effect on Performance of solvent and adjuvant.Another characteristics of percutaneous dosing are that the absolute bioavailability of medicine is low, merely increase the interior drug concentrations of transdermal delivery system prescription and make the absolute bioavailability of medicine reduce more, also cause the waste of medicine and the raising of preparation cost.
The key of percutaneous dosing technology also just is to manage to overcome the barrier action of skin, improves the percutaneous rate of medicine, makes percutaneous dosing can satisfy the needs of effective blood drug concentration, reaches the purpose for the treatment of disease.From (2) formula of above-mentioned Fick's law as can be seen, the percutaneous rate of medicine is directly proportional with the drug level of skin surface.Therefore there is researcher that the drug depot of percutaneous dosing is made the saturated solution of medicine, to improve the percutaneous rate of medicine.
But so, medicine is separated out because of the change of the external condition in storing transportation and medication process etc. easily, forms crystal or solid granulates.Especially the dissolved again process of crystal is slow for storage storehouse internal solid granule, the drug level of system is reduced, the migration of blocking medicine in drug depot, thereby reduce the percutaneous rate of medicine, also can be because of being deposited on skin surface, reduce the actual infiltrating area of medicine, thereby reduced the infiltration rate of medicine.Therefore, so in fact played the opposite effect that things turn out contrary to one's wishes.On the other hand, even overcome aforementioned disadvantages, medicine can not form solid granulates in the medication process, but along with medicine constantly penetrates skin, drug concentrations reduces thereupon gradually in the storage storehouse, on the one hand the permeation rate of drugs is slowed down thereupon, also the controlled-release effect (zero-order release) of transdermal delivery system is produced harmful effect on the other hand.In addition, adopt the absolute bioavailability low (ratio that promptly enters the dosage in body circulation medicine and the drug depot is low) of the method medicine of transdermal administration, medicine is made saturated solution in the storage storehouse, and actually transmitted medication amount increase more after a little while, can further reduce bioavailability of medicament, cause the increase of the preparation cost of the waste of medicine and transdermal delivery system.
The research of existing transdermal delivery system focuses on the improvement research to aspects such as drug level, promoter, solvents, mostly to improve effective blood drug concentration.Disclose a kind of compound transdermal administration plaster of adhesion that contains medicine and preparation method thereof as patent of invention ZL95191979.2, in this description the medicine that can be by percutaneous drug delivery and the mechanism of action of forming transdermal enhancer, solvent and the promoter of drug depot thereof have all been made detailed description.Make cell seal the chemical compound of imbalance and the binary system of solvent as transdermal enhancer for making cell seal the chemical compound and the solvent of imbalance or contain.
Summary of the invention
For improving the transmission speed of medicine, improve the low shortcoming of percutaneous dosing absolute bioavailability, the invention provides a kind of transdermal delivery system, can improve drug level in the drug depot of transdermal delivery system to increase the percutaneous rate of medicine, can improve the controlled-release effect and the absolute bioavailability of percutaneous dosing again, strengthen the curative effect of medicine, reduce the waste of medicine, reduce the preparation cost of transdermal delivery system.
A kind of transdermal delivery system comprises:
One drug depot is formed the gel medicine layer by medicine, solvent, transdermal enhancer and gelating agent;
One adsorption layer is made up of the solvent adsorption material of the solvent in the drug storeroom;
One sealing coat, non-woven fabrics or semipermeable membrane sealing coat that gaseous state or liquid solvent are seen through smoothly;
Described adsorption layer can be fitted in from the rightabout of pressing close to skin of drug depot on the sealing coat on the drug depot.
The consisting of of described drug depot (percentage by weight): medicine 1～10%; Gelating agent 1～15%; Transdermal enhancer 3～10%; Medicine stabilizing agent 1-3%; The pharmaceutically acceptable solvent surplus of energy dissolved substance.
The gelating agent of described drug depot is selected from the conventional material that uses in this area, as the compositions of one or more materials in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, ethyl cellulose, cellulose acetate-phthalate, methylcellulose, gelatin, arabic gum, starch, polyethylene, polyvinyl alcohol, polybutadiene, polyisoprene, polyisocyanate, polysiloxanes, polyurethane, the poly-ethyl-methyl acrylate.
Described transdermal enhancer is selected from this area the conventional material that uses, as one or more the compositions in 1-dodecyl azacyclo--2-ketone, propylene glycol, glycerol, oleic acid, poloxamer, seven yuan of azacyclo-s of 1-farnesyl--2-ketone, seven yuan of azacyclo-s of 1-geranyl-2-ketone, 2-pyrrolidone, N-N-methyl 2-pyrrolidone N-, dimethyl sulfoxine, dimethyl formamide, dimethyl acetylamide, the lecithin.
A kind of transdermal delivery system, generalized theory exactly medicine and transdermal enhancer and relevant adjuvant etc. are made drug depot, and medicine is to be dissolved in the storage storehouse with unsaturated low concentration.When drug depot is applied ointment or plaster when carrying out administration on skin, with the adsorbing material of certain amount of solvent the rightabout of pressing close to skin from drug depot, slowly take out partial solvent with certain speed, owing to be slowly to take out partial solvent from the rightabout in storage storehouse, medicine forms certain Concentraton gradient in the storage storehouse, increased the migration rate of medicine in the storage storehouse, thereby make storage storehouse and contact skin interface energy reach higher concentration (saturated or near saturated concentration) very soon, improve the transdermal infiltration rate of medicine with this.On the other hand, in the time of the medicine administration through skin, because medicine has bigger migration rate in the storage storehouse, at medicine in dermal osmosis, medicine can add to the interface of drug-supplying system and skin again in time, make the drug level of skin surface keep higher and constant, this has not only guaranteed maximum percutaneous rate from the drug level aspect, also helps the controlled-release effect that medicine is kept zero-order release.In addition, take out from the opposite direction of drug depot and to desolvate, even have the small amount of solid state medicine to separate out at the outer surface layer of storing the storehouse in the one side that extracts solvent, owing to store the grid that the viscosity of thickening agent in the storehouse is big and form, solid granulates is difficult to move to skin surface obstruction medicine to dermal osmosis.So, therefore the drug level in the simple increase drug depot, the absolute bioavailability of medicine also can improve.
Adsorption layer is slowly to extract partial solvent from the rightabout that drug depot is pressed close to skin, thereby the both sides that make drug depot form certain concentration difference, to improve the migration rate of medicine in the storage storehouse, thereby make the medicine of skin surface in administration through skin, can in time be replenished, keep higher drug transdermal speed and make it stable percutaneous rate administration to reach, reach the purpose of controlled release (constant speed administration) administration by this.Therefore, the speed of the extraction solvent of adsorption layer and adsorbance are to make the drug depot both sides form the deciding factor of debita spissitudo difference.And adsorption layer extracts the speed of solvent and the performance that adsorbance not only depends on adsorbing material, and solvent depends on also that through the performance of the isolating membrane (or non-woven fabrics) between adsorption layer and drug depot drug depot keeps the ability of solvent.It is that volatilization ability by performance, concentration, viscosity and the solvent of the framework material in storage storehouse itself determines that drug depot keeps the ability of solvent.Therefore, the different drug depots of forming want comprehensive various factors to screen the adsorption layer suitable with optimization by experiment.Thereby make adsorption layer extract solvent, so that keep suitable concentration difference in the both sides of drug depot with suitable speed.
The concentration difference of drug depot both sides is to impel medicine to the skin surface motive for migration.Suitable concentration difference is meant that under this Concentraton gradient medicine can be kept the concentration stabilize of medicine at skin surface to the speed of skin surface migration in the storage storehouse, and this moment, medicine had optimum percutaneous rate.
The selection of adsorbing material and proportioning will be determined according to the moisture-retaining capacity of drug depot and solubility property, the Release Performance of medicine.Its purpose will guarantee that exactly medicine can constant speed see through skin barrier, increases the transit dose and the constant speed release medicine of medicine.
The adsorbing material of solvent of the present invention is selected from acrylic compounds adsorbent resin, film or sponge-like body; Methacrylic adsorbent resin, film or sponge-like body; Carboxycellulose class absorbent material and polyhydroxy starch based absorbent material; Kiselgel A; Calcium chloride, sodium sulfate class inorganic salt absorbent material, or the multicomponent composite of aforementioned adsorbing material.
A kind of transdermal delivery system of the present invention is particularly useful for the percutaneous dosing of water soluble drug propranolol hydrochloride, verapamil hydrochloride or chlorpromazine hydrochloride.
Select absorbent material as adsorption layer for water miscible medicine example hydrochloric acid Propranolol, chlorpromazine hydrochloride and verapamil hydrochloride, preferably select the polymer adsorbing material of different performance and absorbability, this is because the macromolecular material water absorbing capacity is strong, and can not pollute drug depot because of the composition dissolving.Also can use the mixture of polymer adsorbing material and inorganic absorbent material,, make it more effectively in effective administration time, to impel the drug depot ground constant speed release medicine of can maximum limiting the quantity of by this to regulate the adsorption isotherm of adsorption layer.
According to above-mentioned principle, a kind of transdermal delivery system of the present invention comprises:
The consisting of of described drug depot (percentage by weight): propranolol hydrochloride 1～10%; Hydroxypropyl emthylcellulose 1～5%; Polyvinyl alcohol 1～10%; Propylene glycol 2～6%; Oleic acid 1-2%; Laurel nitrogen ketone 1～4%; Polyethylene Glycol 1-3%; With the injection water as solvent; Described adsorption layer is the mixture of discolour silica gel and acrylic acid High hydrophilous resin; Described sealing coat is a non-woven fabrics.
Transdermal delivery system of the present invention has following outstanding advantage:
A) be coated with the drug-supplying system of adsorbing material, absolute bioavailability is higher than the drug-supplying system that does not add adsorbing material, and this cost that helps reducing transdermal delivery system reduces the waste of medicine.
B) drug-supplying system that is added with adsorbing material time of keeping effective blood drug concentration has prolonged 2-3 doubly than the system of solubilizer adsorbing material not, has reduced patient's medication number of times, has increased the compliance of patient's medication.
C) be added with the transdermal delivery system of adsorption layer, can better stablize the percutaneous rate of medicine, impel the medicine constant release, to obtain stable blood drug level.
D) another the most outstanding advantage of this percutaneous drug-supplying system can be avoided the first pass effect of hepar of oral administration exactly.For serious medicines of this class first pass effect of hepar effect such as propranolol hydrochlorides, percutaneous dosing will improve bioavailability of medicament and therapeutic effect greatly.
Description of drawings
Fig. 1 is a structural representation of the present invention;
Fig. 2 is a using method sketch map of the present invention;
The adsorption isotherm line chart of Fig. 3 adsorption layer;
Fig. 4 is the ultraviolet spectrogram of 0.01% azone;
Fig. 5 is the ultraviolet spectrogram of propylene glycol;
Fig. 6 is the ultraviolet spectrogram of propranolol hydrochloride;
Fig. 7 propranolol hydrochloride is at the light absorption value at 291nm place and the linear relationship chart between concentration
Fig. 8 is the release curve chart of the propranolol hydrochloride transdermal delivery system of not solubilizer adsorbing material;
Fig. 9 is the release curve chart of propranolol hydrochloride transdermal delivery system of the present invention.
The specific embodiment
With water miscible medicines such as propranolol hydrochloride, verapamil hydrochloride or chlorpromazine hydrochlorides is model drug, with polyvinyl alcohol (PVA), hydroxypropyl emthylcellulose (HPMC) etc. is the skeleton macromolecular material, is transdermal enhancer with propylene glycol, Laurel nitrogen ketone (Azone), carbamide, oleic acid etc.Be prepared into the gel-type drug depot 1 of percutaneous dosing according to the prescription that configures; Again with discolour silica gel, polyacrylic acid superabsorbent or high-absorbent materials such as carboxycellulose type and starch type High hydrophilous resin adsorbing material 3 as solvent, 3 of drug depot 1 and adsorbing materials separate as sealing coat 2 with non-woven fabrics or semipermeable membrane, form transdermal delivery system of the present invention shown in Figure 1.
Using method is that 1.5 months pig skin of back 4 is a skin substitute products with the growth stage as shown in Figure 2, and the actual usable floor area of Corii Sus domestica is 50.2cm under study for action
2, the total amount of at every turn supplying with drug depot is about 10g, the thickness in storage storehouse is 2mm; And with 0.01N PBS buffer (pH=7.3) for the dispersion solutions of sink conditions is provided.In the Franz diffusion cell, carry out percutaneous dosing experiment in 37 ℃, the 4ml that takes a sample detects per 24 hours sample analysis after 9 hours per half an hour before 9 hours at drug release time.And drug depot under the same terms and the experimental result of transdermal delivery system of the present invention on Corii Sus domestica that is coated with the solvent adsorption material compared, and experimental result is carried out repeatability verify.
Embodiment:
1) prescription
Drug depot 1:
The prescription of the drug depot of verapamil hydrochloride and chlorpromazine hydrochloride is the same, just changes model drug in the above-mentioned prescription into verapamil hydrochloride or chlorpromazine hydrochloride.
Adsorption layer 3:
Material: behind discolour silica gel 5g and the C2-10 type acrylic acid High hydrophilous resin 1g mix homogeneously as the solvent adsorption material of drug-supplying system.
Sealing coat 2:
Material: adopt permeable and the good non-woven fabrics of permeability.
Detect adsorption rate and the adsorbance of adsorption layer down at 37 ℃, draw its adsorption isotherm the solvent in the drug depot.According to its adsorption isotherm adsorption layer was gone up adsorption solvent 4 hours at blank gel (gel that does not add medicine), the excessive adsorption rate of adsorption layer when initial to eliminate.And then adsorption layer transferred on the drug depot.This processing procedure can be finished when preparing adsorption layer during practical application, the patient just can directly cover adsorption layer on the drug depot when medication like this, removes pretreated trouble from.
2) detection method of drug level in the diffusion cell
Ultraviolet spectrophotometry detects transdermal drug level in the Franz diffusion cell, the detection wavelength is 291nm, at first formulate the standard curve of propranolol hydrochloride, detect sample that different time obtains in the Franz diffusion cell light absorption value again, be converted into drug level from standard curve at 291nm.
3) test result
By the adsorption layer of aforementioned prescription configuration, its adsorption isotherm is seen Fig. 3.
As can be seen from Figure 3, adsorption layer big adsorption rate of adsorbance before 4 hours is fast.This is unfavorable for forming stable Concentraton gradient in drug depot.Therefore, adsorption layer must cover on blank gel 4 hours before application in advance, to eliminate the too fast phenomenon of initial adsorption.Fig. 3 shows, the adsorption layer of our screening, and adsorption rate is balanced and stable after 4 hours.The speed of average adsorption solvent is 0.024g/hr.Stable adsorption rate helps forming stable Concentraton gradient in drug depot.
Be added with solvent adsorption material and the not external release research of two kinds of transdermal delivery systems of solubilizer adsorbing material according to preceding method, the result is as follows:
At first set up the detection method of dispersion solutions Chinese medicine concentration.Fig. 4,5,6 is respectively the UV scanning collection of illustrative plates of azone, propylene glycol and propranolol hydrochloride.Comparison diagram 4,5,6 has bigger absorption at 291nm place propranolol hydrochloride as can be known, and azone and propylene glycol almost do not absorb.Therefore selecting 291nm is the ultraviolet detection wavelength of Propranolol in the diffusion cell.
Fig. 7 is the light absorption value of propranolol hydrochloride and the standard curve of concentration, and it is that 1 μ g/ml has good linear relationship in the concentration range of 10 μ g/ml that Fig. 7 shows between the light absorption value of propranolol hydrochloride and concentration in concentration.We just can detect the light absorption value of the sample of different drug release times at the 291nm place like this, and contrast Fig. 6 just can try to achieve different transdermal medication amount of period.
Fig. 8 and Fig. 9 are respectively solubilizer adsorbing materials and be added with the typical release curve of Propranolol transdermal delivery system (each experiment all repeats 5 times, and 5 times result all can well reappear) of solvent adsorption material not.As can be seen from Figure 8, only be 0.1036g through the total amount of 72 hours transdermal administrations, and drug release rate is very fast before 24 hours, average rate of releasing drug is 81.52 μ g/cm
2H.The release slope of a curve of system approaches zero after 24 hours, and system's transdermal administration amount is very little, has only the medicine of minute quantity to see through Corii Sus domestica.
Fig. 9 shows, is added with the drug-supplying system of solvent adsorption material, and the drug transdermal total amount is 0.19687g in 72 hours, much larger than the drug delivery system of solubilizer adsorbing material not.This has just improved the absolute bioavailability of drug-supplying system undoubtedly, is 1.9 times of the absolute bioavailability of solubilizer adsorbing material system not.From figure, it can also be seen that, the good linear of system release curve in 48 hours, this shows that system is by the administration of skin constant speed in 48 hours.Its average drug release rate is 71.52 μ g/cm
2H.In 48～72 hours period, still have higher injection speed 21.8 μ g/cm
2H.
Tolerating area with the percutaneous dosing maximum of generally acknowledging is 30cm
2Calculate, the injection speed that is added with the transdermal delivery system of the present invention of solvent adsorption material is 71.52 μ g/cm
2H, then the dosage of every day is 51.49mg/d, satisfies the needs of the dose therapeutically effective of Propranolol, shows that the present invention has broad application prospects and using value.
The zoopery well afoot of transdermal delivery system of the present invention, preliminary result shows that this system is at the external percutaneous dosing that carries out of White Rabbit, and is respond well, can reach the effective blood drug concentration of therapeutical effect, and the intravital blood concentration fluctuation of White Rabbit is very little.
When being model drug with verapamil hydrochloride or chlorpromazine hydrochloride, experimental technique is identical when being model drug with the propranolol hydrochloride, when detecting the percutaneous rate of verapamil hydrochloride or chlorpromazine hydrochloride, also can adopt spectrophotography, select 278nm (verapamil hydrochloride) or 306nm (chlorpromazine hydrochloride) for detecting wavelength respectively, because they have absorption maximum at these two wavelength respectively, and from top Fig. 3 and Fig. 4 as can be seen propylene glycol and azone in can the not exert an influence interference of testing result of 278nm or 306nm.These two kinds of medicines are all water-soluble, and its drug depot selects for use water to make solvent equally.Therefore, be that the adsorption layer that uses among the embodiment of model drug is equally applicable to verapamil hydrochloride and chlorpromazine hydrochloride at propranolol hydrochloride.
Adsorption layer is made in inorganic salts such as the material of the same available energy adsorption moisture of adsorption layer such as carboxycellulose class absorbent material and polyhydroxy starch based absorbent material, Kiselgel A calcium chloride, sodium sulfate or its combination.
Experimental result shows: the method that adopts adsorbing material slowly to take out partial solvent, help increasing the drug level of skin surface, increase the percutaneous rate of medicine, and can keep constant percutaneous rate and blood drug level, prolong effective administration time of transdermal delivery system.
Claims (7)
1. transdermal delivery system comprises:
One drug depot is formed the gel medicine layer by medicine, solvent, transdermal enhancer and gelating agent;
One adsorption layer is made up of the solvent adsorption material of the solvent in the drug storeroom;
One sealing coat, non-woven fabrics or semipermeable membrane sealing coat that gaseous state or liquid solvent are seen through smoothly;
Described adsorption layer can be fitted in from the rightabout of pressing close to skin of drug depot on the sealing coat on the drug depot.
2. a kind of transdermal delivery system according to claim 1 is characterized in that: the consisting of of described drug depot (percentage by weight): medicine 1～10%; Gelating agent 1～15%; Transdermal enhancer 3～10%; Medicine stabilizing agent 1-3%; The pharmaceutically acceptable solvent surplus of energy dissolved substance.
3. a kind of transdermal delivery system according to claim 1 and 2 is characterized in that: the gelating agent of described drug depot is selected from the compositions of one or more materials in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, ethyl cellulose, cellulose acetate-phthalate, methylcellulose, gelatin, arabic gum, starch, polyethylene, polyvinyl alcohol, polybutadiene, polyisoprene, polyisocyanate, polysiloxanes, polyurethane, the poly-ethyl-methyl acrylate.
4. a kind of transdermal delivery system according to claim 1 and 2 is characterized in that: described transdermal enhancer is selected from one or more the compositions in 1-dodecyl azacyclo--2-ketone, propylene glycol, glycerol, oleic acid, poloxamer, seven yuan of azacyclo-s of 1-farnesyl--2-ketone, seven yuan of azacyclo-s of 1-geranyl-2-ketone, 2-pyrrolidone, N-N-methyl 2-pyrrolidone N-, dimethyl sulfoxine, dimethyl formamide, dimethyl acetylamide, the lecithin.
5. a kind of transdermal delivery system according to claim 1 and 2 is characterized in that: the adsorbing material of solvent is selected from acrylic compounds adsorbent resin, film or sponge-like body; Methacrylic adsorbent resin, film or sponge-like body; Carboxycellulose class absorbent material and polyhydroxy starch based absorbent material; Kiselgel A; Calcium chloride, sodium sulfate class inorganic salt absorbent material, or the multicomponent composite of aforementioned adsorbing material.
6. a kind of transdermal delivery system according to claim 1 and 2 is characterized in that: described medicine is a kind of in water soluble drug propranolol hydrochloride, verapamil hydrochloride or the chlorpromazine hydrochloride.
7. a kind of transdermal delivery system according to claim 6 comprises:
The consisting of of described drug depot (percentage by weight): propranolol hydrochloride 1～10%; Hydroxypropyl emthylcellulose 1～5%; Polyvinyl alcohol 1～10%; Propylene glycol 2～6%; Oleic acid 1-2%; Laurel nitrogen ketone 1～4%; Polyethylene Glycol 1-3%; With the injection water as solvent;
Described adsorption layer is the mixture of discolour silica gel and acrylic acid High hydrophilous resin;
Described sealing coat is a non-woven fabrics.
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| CNB2004100081217A CN100386073C (en) | 2004-03-03 | 2004-03-03 | Transdermal drug administering system |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102871956A (en) * | 2012-10-29 | 2013-01-16 | 中南大学湘雅医院 | Propranolol hydrochloride gel for treating infant superficial hemangioma |
| CN105434336A (en) * | 2015-04-03 | 2016-03-30 | 武汉科福新药有限责任公司 | Propranolol hydrochloride gel preparation for external use and preparation method and application thereof |
| CN107510884A (en) * | 2017-09-30 | 2017-12-26 | 河南汇博医疗股份有限公司 | A kind of Silica hydrogel elasticity scar plaster and preparation method thereof |
| CN108451897A (en) * | 2018-03-21 | 2018-08-28 | 中国人民解放军南京军区福州总医院 | A kind of Propranolol Hydrochloride-polyvinyl alcohol cellular aqueogel and its preparation method and application |
| CN112999144A (en) * | 2021-01-27 | 2021-06-22 | 杭州医学院 | Iontophoresis transdermal drug delivery system |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6039977A (en) * | 1997-12-09 | 2000-03-21 | Alza Corporation | Pharmaceutical hydrogel formulations, and associated drug delivery devices and methods |
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2004
- 2004-03-03 CN CNB2004100081217A patent/CN100386073C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102871956A (en) * | 2012-10-29 | 2013-01-16 | 中南大学湘雅医院 | Propranolol hydrochloride gel for treating infant superficial hemangioma |
| CN102871956B (en) * | 2012-10-29 | 2014-03-05 | 中南大学湘雅医院 | Propranolol hydrochloride gel for treating infant superficial hemangioma |
| CN105434336A (en) * | 2015-04-03 | 2016-03-30 | 武汉科福新药有限责任公司 | Propranolol hydrochloride gel preparation for external use and preparation method and application thereof |
| CN105434336B (en) * | 2015-04-03 | 2019-01-29 | 武汉科福新药有限责任公司 | Propranolol Hydrochloride external-use gel preparation and its preparation method and application |
| CN107510884A (en) * | 2017-09-30 | 2017-12-26 | 河南汇博医疗股份有限公司 | A kind of Silica hydrogel elasticity scar plaster and preparation method thereof |
| CN108451897A (en) * | 2018-03-21 | 2018-08-28 | 中国人民解放军南京军区福州总医院 | A kind of Propranolol Hydrochloride-polyvinyl alcohol cellular aqueogel and its preparation method and application |
| CN112999144A (en) * | 2021-01-27 | 2021-06-22 | 杭州医学院 | Iontophoresis transdermal drug delivery system |
| CN112999144B (en) * | 2021-01-27 | 2023-03-21 | 杭州医学院 | Ionic electroosmosis transdermal drug delivery system |
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| Publication number | Publication date |
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| CN100386073C (en) | 2008-05-07 |
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