CN1720908A - Beta-Asarone transdermal plaster - Google Patents
Beta-Asarone transdermal plaster Download PDFInfo
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Abstract
The invention belongs to pharmaceutical field, relate in particular to the transdermal patch that contains beta-Asarone.The transdermal patch of beta-Asarone of the present invention is by comprising that bin-storing layer, backing layer, adhesive layer and protective layer form, and wherein bin-storing layer consists of the beta-Asarone of 0.1%～40% (mass percent) and acceptable substrate pharmaceutically.The transdermal patch of beta-Asarone of the present invention has antiepileptic action, reduces epilepsy number of times and persistent period, and can protect cranial nerve cell, alleviates the brain injury effect of epilepsy to the patient.The present invention can discharge medicine at the appointed time continually and steadily, has that curative effect is clear and definite, a steady quality, safety is good, easy to use, side effect is little advantage.
Description
Invention field
The present invention relates to pharmaceutical field, relate in particular to the transdermal patch field of containing beta-Asarone.
Technical background
Beta-Asarone is the main component of Rhizoma Acori Graminei volatile oil, and central nervous system, cardiovascular system, respiratory system, digestive system are all had certain pharmacological action.Studies show that: beta-Asarone has dual regulation to the CNS irritability; The apoplexy rat model had alleviate cerebral edema, improve electroencephalogram, improve the effect of hypoxia-bearing capability, and can protect brain cell, significantly suppress brain cortex and hippocampal neurons apoptosis, suppress bax gene expression, and promote bc1-2 gene expression; Beta-Asarone has the effect of vasodilator, platelet aggregation inhibitory activity, points out it that cerebrovascular accident is had preventive and therapeutic effect; Beta-Asarone has inhibitory action to the animal brain electricity.
U.S. Harvard Medical School studies have shown that in the multiple composition of Rhizoma Acori Graminei; α-asaricin; three monomers of beta-Asarone and cis methylisoeugenol shield to the apoptosis of the inductive PC12 cell of amyloid beta; eugenol; beta-Asarone; 3 kinds of monomers of α-asaricin can stop the interior stream of intracellular calcium; the nerve cell death rate is obviously reduced; and the apoptotic cell quantity that A β is caused significantly reduces; has anti-apoptotic effect (Yoshifumi Irie, Wing Ming Keung.Rhizoma acori graminei and its active principlesprotect PC-12 cells from the toxic effect of amyloid-β peptide.Brain Research.2003.963.282-289).The research of Liao etc. points out, Rhizoma Acori Graminei is to the effect of cental system, can explain by the GABA binding site that Rhizoma Acori Graminei acts on dopamine D 1 and D2 receptor and GABA receptor, and confirm that α-asaricin is inoperative in this process.That prompting is worked may be beta-Asarone (Liao JF, Huang SY, Jan YM, Yu LL, Chen CF.Central inhibitory effects of waterextract of Acori graminei rhizoma in mice.J Ethnopharmacol.1998.61 (3) .185-93).Beta-Asarone and α-asaricin are by blocking N (NMDA) receptor; protection brain cortex cell; alleviate neurotoxic injury effect (the Cho J that causes by NMDA or glutamic acid; Ho Kim Y; Kong JY; Ha Yang C; Gook Park C.Protection of cultured rat corticalneurons from excitotoxicity by asarone, a major essential oil component in the rhizomes ofAcorus gramineus.Life Sci.2002.71 (5) .591-599).
The beta-Asarone pharmacokinetic data shows, its half-life at rat blood serum is 52min, transdermal time 3min, peak time 12min reaches peak concentration 3.19mg/L, in each organ (except that liver, kidney), brain has higher distribution, the prompting have first pass effect of hepar (Wu Hongbin, Fang Yongqi. beta-Asarone is in pharmacokinetics in rats. Acta Pharmaceutica Sinica, 2004,39 (10): 836-838).
Transdermal drug delivery system (TTS) is meant after the skin administration, medicine rapid permeability skin, enter blood circulation and play the controlled release preparation of whole body therapeutic effect, the distinct advantages that has: avoided contingent liver first-pass effect of oral administration and gastrointestinal deactivation, improved therapeutic effect; Keep constant blood drug level or pharmacodynamics effect, strengthened therapeutic effect, can not produce the blood drug level peak valley undulatory property that oral administration produces; Prolong action time, reduce the medication number of times, strengthened patient's compliance, be particularly suitable for inaccurate old people is unfamiliar with or is remembered to dosage regimen; Patient independently medication also can end medication at any time.
Summary of the invention
The technical problem that the present invention solves provides safety, side effect is little, the continuous action time is long beta-Asarone transdermal plaster.
The beta-Asarone transdermal plaster that the present invention carried comprises bin-storing layer, backing layer, adhesive layer and protective layer.
The beta-Asarone that bin-storing layer in the beta-Asarone transdermal plaster that the present invention carried consists of 0.1%～40% (mass percent) reaches pharmaceutically acceptable substrate.Wherein bin-storing layer can have following four kinds of forms: membrane controlled release type, viscose decentralized, skeleton diffused, pair micro-reservoirs type, preferably viscose decentralized.
Beta-Asarone can prepare in order to the below method: Rhizoma Acori Graminei adds 8 times of water gagings, by " appendix volatile oil of Chinese pharmacopoeia extracts the Division A League Matches of French Football method, extracts 24 hours, collects volatile oil, volatile oil make with extra care purify beta-Asarone.
Beta-Asarone content better is 5～25% (mass percents) in the beta-Asarone transdermal plaster of the present invention, preferably 10% (mass percent).
The used substrate of viscose decentralized bin-storing layer of the present invention can be aqueous matrix or oleaginous base.
Aqueous matrix in the beta-Asarone transdermal plaster of the present invention is one or more the mixture among ethyl cellulose sodium (EC-Na), methylcellulose (MC-Na), sodium carboxymethyl cellulose (CMC-Na), polyvinyl alcohol (PVA), Polyethylene Glycol (PFG), polyvinylpyrrolidone (PVP), Pseudobulbus Bletillae (Rhizoma Bletillae) glue, tragakanta, arabic gum, Ka Baibo resinoid, sodium alginate, EUDRAGIT (You Teqi) E12.5.Methylcellulose (MC-Na), sodium carboxymethyl cellulose (CMC-Na), polyvinyl alcohol (PVA), Polyethylene Glycol (PFG), polyvinylpyrrolidone (PVP), tragakanta, EUDRAGIT (You Teqi) E12.5 one or more mixture wherein preferably.
Oleaginous base in the beta-Asarone transdermal plaster of the present invention is one or more the mixture among ethyl cellulose (EC), carboxy-propyl cellulose (HPC), EUDRAGIT (You Teqi) E100.
The used substrate of above-mentioned viscose decentralized bin-storing layer is oleaginous base preferably.
When preparation beta-Asarone transdermal plaster of the present invention, stromatolysis forms glue in solvent.The solvent that the present invention uses can be one or more the mixed solvent in water, ethanol, propylene glycol, glycerol, isopropyl alcohol, acetone, the dimethyl sulfoxide.Can preferably use consumption and form according to method known to those skilled in the art.
Above-mentioned viscose decentralized bin-storing layer can contain antiseptic.Antiseptic is wherein one or more mixture of benzoic acid, sodium benzoate, parabens, and consumption is 0.01%～0.3%.
Above-mentioned viscose decentralized bin-storing layer can contain Percutaneous absorption enhancer.Percutaneous absorption enhancer commonly used is wherein one or more mixture of azone, polyoxyethylene nonylphenol ether, poloxamer, Borneolum Syntheticum, menthol, oleic acid, enuatrol, Tweens, phospholipid, glycerol, dimethyl sulfoxide, succinic acid.Azone, menthol, Tweens, dimethyl sulfoxide, succinic acid one or more mixture wherein preferably.The Percutaneous absorption enhancer consumption is 0.015%～5%.
Membrane controlled release type of the present invention can be the single or multiple lift composite membrane.Release-controlled film is ethene-vinyl acetate (EVA) copolymer, polyethylene, polypropylene.Can also use other materials well known by persons skilled in the art as release-controlled film.
Pair micro-reservoirs type involved in the present invention can use behind the aluminum plastic film pressing mold as drug depot, can also use other materials well known by persons skilled in the art as drug depot.
Skeleton diffused beta-Asarone transdermal plaster of the present invention, with the macromolecular material that contains beta-Asarone as framework material, form with backing film, adhesive layer, be divided into two kinds of polymer backbone type beta-Asarone transdermal plaster and porous skeleton type beta-Asarone transdermal plasters.
Polymer backbone type beta-Asarone transdermal plaster of the present invention uses hydrophilic polymer material as skeleton.Hydrophilic polymer material has natural polysaccharide, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylate and polyacrylamide.Also contain wetting agent in the polymer backbone type beta-Asarone transdermal plaster skeleton of the present invention.Wetting agent has water, propylene glycol and low-molecular-weight Polyethylene Glycol (as PEG400).Other materials well known by persons skilled in the art be can also use and consumption and form used.
Porous skeleton type beta-Asarone transdermal plaster of the present invention is made up of backing film, pastille porous skeleton and adhesive layer.The material of porous skeleton can be polrvinyl chloride, polysulfones, Merlon, Polyurethane, cellulose esters.Porous skeleton is immersed in the dispersive medium that contains medicine, and medicine is evenly distributed in the microcellular structure.Dispersive medium can be water, lower alcohols, esters, low-molecular-weight Polyethylene Glycol (as PEG400) and mineral wet goods.
Porous skeleton type beta-Asarone transdermal plaster of the present invention, the porous skeleton material is Triafol T preferably.
Adhesive of the present invention can be polyisobutylene class pressure sensitive adhesive, acrylic compounds pressure sensitive adhesive, silicone rubber pressure sensitive adhesive, rubber cream, better be EUDRAGIT (You Teqi) E12.5, EUDRAGIT (You Teqi) E100, preferably EUDRAGIT (You Teqi) E100.Other adhesive be can select according to method known to those skilled in the art for use, and consumption and form used.
Adhesive layer of the present invention can contain plasticizer.Plasticizer can be wherein one or more mixture of kieselguhr, Kaolin, Pulvis Talci, zinc oxide.Can select consumption and the form used for use according to method known to those skilled in the art.
Backing layer of the present invention can be non-woven fabrics, elastic force adhesive plaster, polyethylene film, polypropylene screen, polychloroethylene film, aluminum plastic film, aluminium foil, scribble the aluminium foil of layer of silicone, scribble silicone aluminium foil, scribble the aluminium foil of polyester and silicone.Can also use other materials well known by persons skilled in the art as backing layer.
The preparation method that the preparation method of beta-Asarone transdermal plaster of the present invention can adopt those skilled in the art to use always, preparation method commonly used is as follows:
Viscose decentralized beta-Asarone transdermal plaster preparation method: 1. substrate, antiseptic, Percutaneous absorption enhancer are dissolved in the solvent, add the beta-Asarone mix homogeneously.2 are coated on aforesaid liquid in the container, place and make solidification forming, promptly get the flaky beta-Asarone substrate that contains.3. by compound mode that bin-storing layer, backing layer, adhesive layer and protective layer is compound, get viscose decentralized beta-Asarone transdermal plaster.
The preparation method of compound membranous type beta-Asarone transdermal plaster: 1. the auxiliary agent with pressure sensitive adhesive, beta-Asarone, pharmaceutically acceptance is dissolved in the solvent, is coated on behind the mix homogeneously on the backing film, forms the coating bin-storing layer, and solvent evaporates is formed bin-storing layer.2. other auxiliary agents with pressure sensitive adhesive, beta-Asarone, pharmaceutically acceptance are dissolved in the solvent, are coated on behind the mix homogeneously on the protecting film, form the coating adhesive layer, and solvent evaporates is formed adhesive layer.3. adhesive layer is compounded on the release-controlled film.4. adhesive layer and bin-storing layer is compound, and cutting obtains compound membranous type beta-Asarone transdermal plaster.
The preparation method of polymer backbone type beta-Asarone transdermal plaster: the 1. hydrophilic polymer material heating for dissolving is formed glue in solvent, add beta-Asarone and suitable surfactant mixture mix homogeneously.2. with above-mentioned glue cooling forming.3. combination backing film and protecting film are packaged to be product.
The preparation method of porous skeleton type beta-Asarone transdermal plaster: 1. beta-Asarone is dissolved in the acetone and other organic solvent.2. add porous skeleton material, mix homogeneously.3. volatilize solvent, it is tiled in the aluminium foil that scribbles pressure sensitive adhesive, stick separate paper, packaging of aluminium foil bag obtains product.
The preparation method of adhesive matrix type beta-Asarone transdermal plaster: 1.Pressure sensitive adhesive is dissolved in forms pressure sensitive adhesive solution in the solvent, add beta-Asarone, mix homogeneously.2. slough bubble, be coated on backing film, dry removing desolvated.3, composite protection film cuts, is packaged into product.
The present invention can discharge medicine at the appointed time continually and steadily, has that curative effect is clear and definite, a steady quality, safety is good, easy to use, side effect is little advantage.
The effect experiment of beta-Asarone transdermal plaster of the present invention is as follows:
1) beta-Asarone vitro skin penetration kinetics test
The standard curve preparation: precision takes by weighing beta-Asarone reference substance 4.4mg, puts in the 50ml volumetric flask, adds dissolve with ethanol and is diluted to scale, preparation storing solution (88 μ g/ml).Accurate absorption 2,1,0.2,0.5ml storing solution are diluted with ethanol to scale in the 10ml measuring bottle, be made into 17.6,8.8,1.76,0.44 μ g/ml beta-Asarone reference substance solution, and sample introduction is measured.With peak area integrated value (X) beta-Asarone mass concentration (Y) is returned, must mark Huaihe River curve Y=3.86 * 10
-4X+6.38 * 10
-3, (r=0.9995).Show that beta-Asarone has the good linear relation at 4.4～1320ng and peak area, precision, study on the stability all reach standard.
Preparation of isolated rat skin and processing: get adult male SD rats, body weight 300g～350g anaesthetizes with 10% chloral hydrate 0.3ml/100g.Get skin of back, strip skin after shaving off hair, remove subcutaneous fat, with ice normal saline flushing 3 times.Skin is put-4 ℃ of refrigerators and preserved, took out in second day, thaw naturally, clean with normal saline flushing.The skin of handling well is fixed on for medicine pond and accepting between the pond, and stratum corneum side is to for the medicine pond, and skin corium contacts with acceptable solution towards accepting the pond.
The preparation of beta-Asarone dicyandiamide solution and reception liquid: get the 0.2mg beta-Asarone and be dissolved in 20ml ethanol, be diluted with water to 100ml, as dicyandiamide solution I; Get the 0.2ml beta-Asarone and the 0.1g Borneolum Syntheticum is dissolved in 20ml ethanol, be diluted with water to 100ml, as dicyandiamide solution II; Get 0.2ml beta-Asarone, 0.1g Borneolum Syntheticum and 1ml aqueous azone and be dissolved in 20ml ethanol, be diluted with water to 100ml, as dicyandiamide solution III; Get 0.2ml beta-Asarone, 0.1g Borneolum Syntheticum and 3ml aqueous azone and be dissolved in 20ml ethanol, be diluted with water to 100ml, as dicyandiamide solution IV; Get 0.2ml beta-Asarone, 0.1g Borneolum Syntheticum and 5ml aqueous azone and be dissolved in 20ml ethanol, be diluted with water to 100ml, as dicyandiamide solution V; Take by weighing 0.9g sodium chloride and be dissolved in 100g 20% ethanol, promptly get and receive liquid.
The Transdermal absorption experiment: rectilinear diffusion cell is accepted the long-pending 6.5ml of being of cell body by supplying the medicine pond and accepting the pond and form, and the effective diffusion area of Chi Kou is 2.8cm
2Diffusion cell places the water bath with thermostatic control circulating box to keep 37 ℃, accepts the mid-magnetic stir bar in pond, constantly stirs with 250r/min speed.Acceptable solution added accept to contact closely in the pond and with skin corium, and note draining bubble from sample tap.Start infiltration diffusion test instrument 30min stable after, the different solvents system that will contain beta-Asarone adds in the medicine pond.0.5,1,2,3,5,7,10,13,23,24h draws acceptable solution 1,1,1,1,2,2,2,5,3,1ml respectively and replenishes the isothermal blank acceptable solution of equivalent simultaneously.The acceptable solution of drawing is crossed 0.45 μ m microporous filter membrane, gets subsequent filtrate and measures.
The percutaneous accumulation infiltration capacity of medicine (M) is calculated: owing to after getting acceptable solution, add the equivalent blank simultaneously and connect liquid at every turn, it is low therefore to record the concentration ratio actual concentration, so different sample point M value is pressed the correction that establishes an equation.
C in the formula
nAcceptable solution measured concentration during for different sample point, V is for accepting cell body long-pending (6.5ml), and Vs (n-1) is the sample volume of different time points, and A is effective diffusion area (2.8cm
2).With the accumulation transit dose time is carried out linear regression, the slope of gained equation is infiltration rate P.
Beta-Asarone vitro skin penetration kinetics result of the test
Table 1 beta-Asarone in 5 kinds of dicyandiamide solutions 24 hours accumulation infiltration capacity M (x ± s, n=6)
| Time/h | The beta-Asarone dicyandiamide solution | ||||
| I | II | III | IV | V | |
| 0.5 1 2 3 5 7 10 13 23 24 | 2.203±0.296 2.499±0.219 3.038±0.330 5.155±1.877 11.685±5.423 29.998±16.195 76.274±32.015 118.434±30.645 315.683±86.967 352.624±87.049 | 2.838±0.776 2.769±0.960 3.147±0.931 3.571±1.142 6.816±3.230 15.578±9.699 30.757±18.529 67.293±38.005 218.245±76.401 231.117±77.072 | 2.226±0.387 2.319±0.389 2.938±0.228 3.713±0.561 7.040±2.574 14.116±6.316 29.364±13.258 * 47.741±19.232 ** 126.941±38.395 **# 146.635±46.512 ** | 2.154±0.293 2.292±0.275 2.947±0.333 3.812±0.260 7.259±1.512 11.553±2.289 21.810±5.016 * 31.957±6.964 **# 78.109±11.433 **# 96.238±14.926 **# | 2.357±0.738 2.491±0.431 2.92±0.542 3.326±0.652 5.308±1.549 * 8.728±3.591 * 14.251±5.846 * 22.617±8.015 **# 65.709±17.890 **##Δ 69.361±18.639 **#Δ |
Annotate: compare with dicyandiamide solution I: * P＜0.05 * * P＜0.01
Compare with dicyandiamide solution H: #P＜0.05 ##P＜0.01
Compare with dicyandiamide solution III: Δ P＜0.05 (table 2 together)
M-t equation and the infiltration rate P (x ± s) of table 2 beta-Asarone in 5 kinds of dicyandiamide solutions
| Dicyandiamide solution | The M-t equation | r | P(μg/cm 2.h) |
| I II III IV V | M＝18.902t-112.49 M＝14.558t-117.91 M＝8.164t-55.18 M＝4.218t-20.03 M＝4.051t-27.91 | 0.9942 0.9991 0.9915 0.9947 0.9969 | 18.902±4.840 14.558±3.727 8.164±2.308**# 4.218±0.618**##Δ 4.051±1.026**##Δ |
2) rat cerebral ischemia-reperfusion injury test
The ischemia-reperfusion brain damage model is made: with chloral hydrate (300mg/kg body weight) intraperitoneal injection of anesthesia, get dorsal position, separate and expose bilateral carotid, and it is standby to put line respectively, after closing bilateral carotid 60min with bulldog clamp folder, perfusion again, sew up wound causes the ischemia-reperfusion brain damage model.
SD rat random packet: high dose group, middle dosage group, low dose group, positive controls, model control group, each treated animal intraperitoneal injection 7d, model control group is given equal-volume normal saline, every day 2 times.After the administration in the 7th day 1 hour, cause the ischemia-reperfusion brain damage model.Before the modeling folder closes common carotid artery, acupuncture needle is inserted the brain skull surface (top layer subperiosteum) of rat, measure and write down the electroencephalogram before the rat serum pipe clamp closes earlier; Then, closed bilateral carotid 60 minutes, write down electroencephalogram simultaneously with the bulldog clamp folder; After folder closed 60 minutes, perfusion was observed 24 hours again, and write down the electroencephalogram when pouring into 24 hours again; Put to death rat, get brain cortex and Hippocampus fast, press the apoptosis situ end labeling and detect neuronal apoptosis.Microscopically observation of cell apoptosis situation.With BJ University of Aeronautics ﹠ Astronautics's pathological image analytical system, quantitative analysis Neuron Apoptosis number (every high power field, amplification 72.5) and apoptosis integration; Bax, Bc1-2 gene protein detect with immunohistochemical method, the apoptosis integration (optical density * area) of quantitative analysis apoptosis cell, cell.All the other cerebral tissue measured moisture contents [weighed after three days by 85 ℃ of oven dry; Brain water content (%)=(wet brain heavy-dried brain is heavy)/wet brain heavy * 100%].
The influence of table 3 pair rat brain electrograph (x ± s)
| Group | Before folder closes | Perfusion again after folder closed during folder closed | |||
| Frequency Hz | Wave amplitude uv | Frequency Hz | Wave amplitude uv frequency Hz | Wave amplitude uv | |
| 10g/L beta-Asarone 20g/L beta-Asarone 40g/L beta-Asarone positive controls model control group | 14.80±2.68 14.20±2.55 15.06±2.56 14.00±2.70 15.10±2.38 | 9.15±2.12 ***ΔΔΔ 8.70±220 ***ΔΔΔ 8.96±2.50 *** ΔΔΔ 10.68± 2.90 *** 7.20±1.49 | 14.2±216 ΔΔΔ13.9±1.97 ΔΔΔ14.9±2.08 ΔΔΔ17.00± 1.95 ***14.15±2.03 | 5.82±1.41 ***ΔΔΔ 1425±3.85 ** 5.78±1.19 ***ΔΔΔ 14.45±3.03 ** 6.15±1.25 ***ΔΔΔ 14.33±2.91 ** 10.35±1.98 *** 14.55± 2.11 *** 4.55±0.78 17.35±2.16 | 5.12±1.01 ***ΔΔΔ 4.98±1.44/ ***ΔΔΔ 538±1.25 ***ΔΔΔ 9.32±2.26 9.10±1.94 |
Annotate: compare: * P＜0.05, * * P＜0.01, * * * P＜0.001 (down together) with model control group
Compare with positive controls: Δ Δ Δ P＜0.001
The influence of table 4 pair rat brain neuronal apoptosis (x ± s, n=10)
| Group | Cortex | Hippocampus | ||
| Apoptosis cell | The apoptosis integration | Apoptosis cell | The apoptosis integration | |
| 10g/L beta-Asarone 20g/L beta-Asarone 40g/L beta-Asarone positive controls model control group | 51.9±36.1 *** 49.5±25.4 *** 48.8±42.2 *** 42.5±38.2 *** 107.8±22.9 | 716.1±255.1 625.0±289.9 664.0±312.5 615.8±303.6 842.8±151.2 | 0.78±0.52 *** 0.81±0.42 *** 0.88±0.54 *** 0.85±0.58 *** 6.32±2.23 | 52.9±20.3 *** 48.0±16.9 *** 49.1±21.4 *** 51.1±18.3 *** 118.3±34.9 |
The influence of table 5 pair BAX gene expression (x ± s, n=10)
| Group | The cortex integration | The Hippocampus integration |
| 10g/L beta-Asarone 20g/L beta-Asarone 40g/L beta-Asarone positive controls model control group | 501.1±185.6 * 491.2±206.0 * 481.9±224.3 ** 475.6±216.5 *** 835.6±330.9 | 522.6±199.8 511.4±239.7 506.4±215.3 ** 509.1±203.8 ** 961.5±363.5 |
The influence of table 6 pair BCL-2 gene expression (x ± s, n=10)
| Group | The cortex integration | The Hippocampus integration |
| 10g/L beta-Asarone 20g/L beta-Asarone 40g/L beta-Asarone positive controls model control group | 140.7±45.6 * 141.8±33.7 * 143.9±35.8 ** 142.5±51.1 * 99.9±25.9 | 68.5±15.5 67.5±17.7 66.8±20.1 65.9±27.6 70.0±23.6 |
3) blood brain permeability test: 50 of healthy mices, body weight 18-22g, male and female half and half, the grouping administration is the same.Behind the last administration 1h, the blue 0.4ml/20g of intravenous injection 1% Evans, sacrificed by decapitation behind the 20min, get brain immediately, with 5ml NS-acetone solution (3: 7) homogenate, placed centrifugal 3000rpm30min 24 hours, supernatant is surveyed oD value (get the normal mouse cerebral tissue and handle equally, be used for school zero) in the 610nm place.
The influence of the normal blood brain of table 10 pair mice permeability (x ± s)
| Group | Number of animals n | The OD value |
| 10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls negative control group | 11 11 11 11 11 | 0.1076±0.0165 * 0.1095±0.0131 ** 0.1212±0.0226 *** 0.1102±0.0252 ** 0.0823±0.0241 |
4) sedation test (sleep experiments)
Get beta-Asarone, add and an amount of pharmaceutically can accept solvent, compound concentration is respectively the solvent of 10g/L, 100g/L, 300g/L, measures drug effect.
Get 50 of healthy mices, male, be divided into high dose group, middle dosage group, low dose group, positive controls, negative control group, the group administration is the same.Behind the last administration 30min, the lumbar injection pentobarbital sodium (0.3%, 55mg/kg), sleep time of occurrence and persistent period (is the sleep index with the animal righting reflex loss) respectively by record.
Table 7 sedation result of the test (x ± s) (min)
| Group | Number of animals (only) | Time for falling asleep | Sleep time |
| 10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls negative control group | 10 10 10 10 10 | 3.18±1.08 *** 3.92±1.44 * 3.83±1.11 ** 3.33±2.81 * 5.58±1.38 | 105.36±14.24 ** 101.33±14.78 ** 70.75±25.29 65.17±20.59 71.42±27.16 |
Annotate: with the negative control group ratio
*P＜0.05
*P＜0.01
* *P＜0.001 (down together)
5) central excitation experiment one (the excited experiment of strychnine):
Get 50 of healthy mices, male, the grouping administration is the same, and behind the last administration 30min, lumbar injection strychnine 1.2mg/kg observes and record convulsions tic number of times, mortality rate and death time.
Table 8 central excitation experiment one (the excited experiment of strychnine) (x ± s)
| Group | Number of animals (only) | The tic number of times | Death toll | Death time (branch) |
| 10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls negative control group | 10 10 10 10 10 | 6.0±2.6 * 7.1±3.6 * 7.9±5.5 ** 6.9±5.0 ** 4.1±3.3 | 8/10 10/10 9/10 8/10 8/10 | 7.6±2.1 ** 6.4±2.6 *** 5.2±3.3 *** 6.2±3.6 ** 11.6±2.4 |
6) central excitation experiment two (the excited experiment of picrotoxin):
50 of female mices, male, the grouping administration is the same, and behind the last administration 30min, lumbar injection picrotoxin 6mg/kg observes and record convulsions tic number of times, mortality rate and death time.
Table 9 central excitation experiment one (the excited experiment of picrotoxin) (x ± s)
| Group | Number of animals (only) | The tic number of times | Death toll | Death time (min) |
| 10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls negative control group | 10 10 10 10 10 | 2.6±0.6 * 2.1±0.6 * 1.9±1.5 ** 2.2±0.5 * 4.2±2.3 | 5/10 2/10 4/10 2/10 4/10 | 15.6±2.1 * 16.4±2.6 * 15.2±3.3 ** 15.5±3.1 * 21.6±5.4 |
7) blood brain permeability test: 50 of healthy mices, body weight 18-22g, male and female half and half, the grouping administration is the same.Behind the last administration 1h, the blue 0.4ml/20g of intravenous injection 1%Evans, sacrificed by decapitation behind the 20min, get brain immediately, with 5ml NS-acetone solution (3: 7) homogenate, placed centrifugal 3000rpm30min 24 hours, supernatant is surveyed OD value (get the normal mouse cerebral tissue and handle equally, be used for school zero) in the 610nm place.
The influence of the normal blood brain of table 10 pair mice permeability (x ± s)
| Group | Number of animals n | The OD value |
| 10g/L beta-Asarone group 20g/L beta-Asarone group 40g/L beta-Asarone group positive controls negative control group | 11 11 11 11 11 | 0.1076±0.0165 * 0.1095±0.0131 ** 0.1212±0.0226 *** 0.1102±0.0252 ** 0.0823±0.0241 |
Above serial experiment result shows:
1. beta-Asarone can improve body's hypoxia tolerance, improves the blood coefficient of oxygen utilization of body, reduces the body oxygen consumption.
2. beta-Asarone can improve blood brain permeability. and medicine can enter cerebral tissue and act on encephalopathy damage position.
3. beta-Asarone can shorten the incubation period of sleeping, and prolongs the length of one's sleep, and sedation is arranged.
4. beta-Asarone can work in coordination with the strychnine innervation, the nerve excitability of picrotoxin is had inhibitory action.
5. beta-Asarone has the effect that alleviates the rat brain edema, can alleviate the cerebral lesion degree, and brain tissue impairment is had the certain protection effect.
6. beta-Asarone has the effect that suppresses brain wave frequency, and the effect of tranquillizing and allaying excitement is arranged.
7. beta-Asarone can alleviate rat brain cortex and hippocampal neurons apoptosis, shows as apoptosis cell minimizing, the reduction of apoptosis integration, alleviates the degree of necrosis of brain cell, thus the protection cerebral tissue.
8. beta-Asarone can suppress rat brain cortex and hippocampal neurons BAX expression of gene, can strengthen the BCL-2 expression of gene, alleviates the generation of apoptosis amount, and brain cell is had the certain protection effect, and then the protection cerebral tissue.
The specific embodiment
Below be specific embodiments of the invention, but be not limited to described embodiment.
Embodiment 1
Aqueous matrix prescription and method for making: polyvinyl alcohol-124 (PVA-124) 1.5g, ethanol 20mL, 1g beta-Asarone, heating in water bath mix homogeneously.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.Complete non-woven fabrics on special mould, coat EUDRAGIT (You Teqi) E100, become backing layer, the flake substrate that will contain beta-Asarone is layered on the backing layer, covers aluminum plastic film again and makes protective layer, and sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 2
Aqueous matrix prescription and method for making: polyvinylpyrrolidone (PVP) 1.0g, isopropyl alcohol 8mL, heating in water bath makes molten, and the 0.0001g beta-Asarone is dissolved in 0.2mL 95% ethanol, joins mixing in the substrate, and adding distil water is made into 10mL.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.Complete polyethylene film on special mould, coat EUDRAGIT (You Teqi) E12.5, become backing layer, the flake substrate that will contain beta-Asarone is layered on the backing layer, covers aluminum plastic film again and makes protective layer, and sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 3
Aqueous matrix prescription and method for making: methylcellulose (MC-Na) 0.7g, sodium carboxymethyl cellulose (CMC-Na) 0.5g, arabic gum 0.5g, water 10mL, oleic acid 0.5mL, azone 1mL, sodium alginate 1.0g, add and contain 0.2% benzoic distilled water immersion certain hour, heating in water bath makes molten, and the 0.2g beta-Asarone is dissolved in 1mL 95% ethanol, join mixing in the substrate, adding distil water is made into 20mL.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.On mould, complete elastic plastic cloth,, coat EUDRAGIT (You Teqi) E100 as backing layer; become backing layer, the flake substrate that will contain beta-Asarone is layered on the backing layer, covers aluminum plastic film again and makes protective layer; sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 4
Aqueous matrix prescription and method for making: polyvinyl alcohol-124 (PVA-124) 0.7g, sodium carboxymethyl cellulose (CMC-Na) 0.7g, isopropyl alcohol 5mL, propylene glycol 5mL, tween 80 0.5mL, azone 1mL, tragakanta 1.2g adds the distilled water immersion certain hour that contains 0.3% ethyl hydroxybenzoate, heating in water bath makes molten, the 0.2g beta-Asarone is dissolved in 1mL 95% ethanol, joins mixing in the substrate, adding distil water is made into 20mL.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.Complete polypropylene screen on mould, coat EUDRAGIT (You Teqi) E12.5, become backing layer, the flake substrate that will contain beta-Asarone is layered on the backing layer, covers aluminum plastic film again and makes protective layer, and sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 5
Aqueous matrix prescription and method for making: polyvinyl alcohol-124 (PVA-124) 0.7g, sodium carboxymethyl cellulose (CMC-Na) 0.7g, ethanol 2mL, dimethyl sulfoxide 8, Tween-60 0.5mL, azone 1mL, tragakanta 1.2g adds the distilled water immersion certain hour that contains 0.1% ethyl hydroxybenzoate, 0.1% sodium benzoate, heating in water bath makes molten, the 0.2g beta-Asarone is dissolved in 1mL 95% ethanol, joins mixing in the substrate, adding distil water is made into 20mL.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.Complete polychloroethylene film on mould, coat polyacrylate pressure-sensitive, become backing layer, the flake substrate that will contain beta-Asarone is layered on the backing layer, covers aluminum plastic film again and makes protective layer, and sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 6
Aqueous matrix prescription and method for making: polyvinyl alcohol-124 (PVA-124) 0.7g, EUDRAGIT (You Teqi) E12.50.7g, propylene glycol 5mL, glycerol 5mL, poloxamer 0.5mL, ammonia ketone 1mL, menthol 0.2mL, Pseudobulbus Bletillae (Rhizoma Bletillae) glue 1.2g add the distilled water immersion certain hour that contains 0.1% ethyl hydroxybenzoate, 0.1% methyl hydroxybenzoate, heating in water bath makes molten, the 0.2g beta-Asarone is dissolved in 1mL 95% ethanol, joins mixing in the substrate, adding distil water is made into 20mL.The stand is applied in the culture dish, places and makes solidification forming, promptly gets the flaky beta-Asarone substrate that contains.On mould, complete aluminum plastic film, coat polyacrylate pressure-sensitive and polyisobutylene class pressure sensitive adhesive, become backing layer; the flake substrate that will contain beta-Asarone is layered on the backing layer; cover aluminum plastic film again and make protective layer, sealing promptly gets beta-Asarone aqueous percutaneous administration patch.
Embodiment 7
Oleaginous base basic recipe and method for making: ethyl cellulose (EC) 10g is dissolved in the 10mL acetone, add 3.3g beta-Asarone mix homogeneously, pour in the mould of completing aluminium foil, evenly coating, volatilize solvent, the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 8
Oleaginous base basic recipe and method for making: carboxy-propyl cellulose (HPC) 10g is dissolved in the 10mL dimethyl sulfoxide, add beta-Asarone 0.53g, mix homogeneously, pour in the mould of completing the aluminium foil that scribbles layer of silicone, evenly coating, volatilize solvent, the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 9
Oleaginous base basic recipe and method for making: EUDRAGIT (You Teqi) E10010g, beta-Asarone 2g, Kaolin 5g, succinic acid 1g, azone 1g.EUDRAGIT E100 and succinic acid, azone are dissolved in ethanol, the isopropyl alcohol mixed solvent, add beta-Asarone and make dissolving, add the Kaolin mix homogeneously, pour in the mould of completing the aluminium foil that scribbles silicone, evenly coating, volatilize solvent, the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 10
Oleaginous base basic recipe and method for making: EUDRAGIT (You Teqi) E1005g, ethyl cellulose (EC) 5g, beta-Asarone 2.5g, kieselguhr 5g, succinic acid 1g, dimethyl sulfoxide 1.2g.
EUDRAGIT E100, ethyl cellulose (EC), succinic acid, dimethyl sulfoxide are dissolved in ethanol, the isopropyl alcohol mixed solvent, add beta-Asarone, make dissolving, add the kieselguhr mix homogeneously, pour in the mould of completing the aluminium foil that scribbles polyester and silicone, evenly coating volatilizes solvent, and the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 11
Oleaginous base basic recipe and method for making: carboxy-propyl cellulose (HPC) 4g, ethyl cellulose (EC) 6g, beta-Asarone 1.5g, succinic acid 1g, menthol 1.5g.
Carboxy-propyl cellulose (HPC), ethyl cellulose (EC), succinic acid, menthol are dissolved in ethanol, the acetone mixed solvent, add beta-Asarone, make dissolving, pour in the mould of completing aluminium foil, evenly coating volatilizes solvent, and the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 12
Oleaginous base basic recipe and method for making: EUDRAGIT (You Teqi) E1005g, ethyl cellulose (EC) 5g, beta-Asarone 2.0g, Pulvis Talci 5g, enuatrol 1g, dimethyl sulfoxide 1.2g.
EUDRAGIT E100, ethyl cellulose (EC), enuatrol are dissolved in ethanol, the mixed with propylene glycol solvent, add beta-Asarone, make dissolving, add the Pulvis Talci mix homogeneously, pour in the mould of completing aluminium foil, evenly coating volatilizes solvent, and the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 13
Oleaginous base basic recipe and method for making: carboxy-propyl cellulose (HPC) 4g, ethyl cellulose (EC) 6g, beta-Asarone 1.5g, Kaolin 2g, Pulvis Talci 3g, phosphatidase 11 g, glycerol 2mL.
Carboxy-propyl cellulose (HPC), ethyl cellulose (EC), phospholipid are dissolved in the mixed solvent of glycerol and isopropyl alcohol, add beta-Asarone, make dissolving, add Pulvis Talci, Kaolin mix homogeneously, pour in the mould of completing aluminium foil, evenly coating volatilizes solvent, and the stripping and slicing encapsulation promptly gets beta-Asarone oiliness percutaneous administration patch.
Embodiment 14
Reservoir devices prescription and method for making: card uncle ripple 974P NF 10g, beta-Asarone 2g, menthol 0.5g, azone 1g, glycerol 5mL.To block uncle's ripple 974P NF and be dissolved in the 30mL water, fully swelling adds glycerol, stirs, and gets substrate; With beta-Asarone, menthol, azone mix homogeneously, be added in the substrate, fully mix, add in the ready made drug depot, one side ethene-vinyl acetate (EVA) the film sealing by fusing of storage storehouse opening, another side is attached on the elastic force adhesive plaster that scribbles acrylate pressure sensitive adhesive, covers separate paper again, sealing promptly gets the reservoir devices patch.
Embodiment 15
Multilamellar film controlling type patch prescription and method for making: beta-Asarone 2g, PVA1788 20g, water-borne acrylic type pressure sensitive adhesive 5g, tween 80 0.5mL places an amount of 70% (V/V) ethanol, reflux makes dissolving, in mould middle berth film, lyophilization, demoulding, use the curtain coating technology pressure-sensitive adhesive coating, with the non-woven fabric compounded beta-Asarone TDD that gets product.Wherein TDD1 is PVA rete (containing the recipe quantity penetration enhancer), spreads pastille pressure-sensitive adhesive layer (containing the recipe quantity penetrating agent) outward; TDD2 only is the PVA rete; The blank pressure sensitive adhesive in the outer shop of the PVA film of TDD3; TDD4 only is the pastille pressure-sensitive adhesive layer.
Embodiment 16
Porous skeleton type beta-Asarone transdermal plaster prescription and method for making:
Beta-Asarone 0.5g, be dissolved in the 2g acetone, fine strip shape Triafol T 10g be impregnated in the acetone soln that contains beta-Asarone, after Triafol T fully absorbs medicinal liquid, pick up the Triafol T bar, volatilize solvent, cut into definite shape, be tiled in the aluminium foil backing layer central authorities that scribble Polyisobutylene PSA, stick separate paper again, with the aluminium foil bag encapsulation, promptly.
Embodiment 17
Porous skeleton type beta-Asarone transdermal plaster prescription and method for making:
Beta-Asarone 1g, be dissolved in the 5g acetone, fine strip shape Triafol T 15g be impregnated in the acetone soln that contains beta-Asarone, after Triafol T fully absorbs medicinal liquid, pick up the Triafol T bar, volatilize solvent, cut into definite shape, be tiled in the aluminium foil backing layer central authorities that scribble the silicone rubber pressure sensitive adhesive, stick separate paper again, with the aluminium foil bag encapsulation, promptly.
Embodiment 18
Porous skeleton type beta-Asarone transdermal plaster prescription and method for making:
Beta-Asarone 0.7g, be dissolved in the 4g acetone, fine strip shape Triafol T 103g be impregnated in the acetone soln that contains beta-Asarone, after Triafol T fully absorbs medicinal liquid, pick up the Triafol T bar, volatilize solvent, cut into definite shape, be tiled in the aluminium foil backing layer central authorities that scribble Polyisobutylene PSA and silicone rubber pressure sensitive adhesive, stick separate paper again, with the aluminium foil bag encapsulation, promptly.
Embodiment 19
Porous skeleton type beta-Asarone transdermal plaster prescription and method for making:
Beta-Asarone 00.8g, be dissolved in the 3g acetone, fine strip shape Triafol T 11 be impregnated in the acetone soln that contains beta-Asarone, after Triafol T fully absorbs medicinal liquid, pick up the Triafol T bar, volatilize solvent, cut into definite shape, be tiled in the aluminium foil backing layer central authorities that scribble Polyisobutylene PSA, stick separate paper again, with the aluminium foil bag encapsulation, promptly.
Embodiment 20
Polymer backbone type beta-Asarone transdermal plaster prescription and method for making:
Prescription: beta-Asarone 1.0g, EUDRAGIT E100 1.6g, glyceryl monolaurate 1.9g, isopropyl myristate 0.57g, succinic acid 0.13g.
Precision takes by weighing recipe quantity EUDRAGIT E100, glyceryl monolaurate, isopropyl myristate, add an amount of solvent [acetone-isopropyl alcohol-ethanol (21.0: 2.3: 11.7, w/w)], ultrasonic dissolution, add the recipe quantity succinic acid, add beta-Asarone behind the ultrasonic dissolution, mixing behind the ultrasonic dissolution.Adopt on the aluminium foil backing layer of certain area of the slow impouring of curtain coating technology and horizontal positioned, volatilize solvent naturally, solidify 10min in 60 ℃ of baking ovens, separate paper promptly on the cooling bonnet.
Embodiment 21
Polymer backbone type beta-Asarone transdermal plaster prescription and method for making:
Prescription: beta-Asarone 2.0g, EUDRAGIT E1006.5g, glyceryl monolaurate 20.45g, isopropyl myristate 1.5g, succinic acid 1.0g, oleic acid 0.5g.
Precision takes by weighing recipe quantity EUDRAGIT E100, glyceryl monolaurate, isopropyl myristate, add an amount of solvent [acetone-isopropyl alcohol-ethanol (21.0: 2.3: 11.7, w/w)], ultrasonic dissolution, add the recipe quantity succinic acid, add beta-Asarone behind the ultrasonic dissolution, and penetrating agent oleic acid 0.6g (perhaps non-refuelling acid), mixing behind the ultrasonic dissolution.Adopt on the aluminium foil backing layer that scribbles silicone of certain area of the slow impouring of curtain coating technology and horizontal positioned, volatilize solvent naturally, solidify 10min in 60 ℃ of baking ovens, separate paper promptly on the cooling bonnet.
Embodiment 22
Polymer backbone type beta-Asarone transdermal plaster prescription and method for making:
Prescription: beta-Asarone 1..5g, EUDRAGIT E1005g, oleic acid 0.6g.
Precision takes by weighing recipe quantity EUDRAGIT E100, add an amount of solvent [acetone-isopropyl alcohol-ethanol (21.0: 2.3: 11.7, w/w)], ultrasonic dissolution adds beta-Asarone, and behind the penetrating agent oleic acid mixing, adopt on the aluminium foil backing layer of certain area of the slow impouring of curtain coating technology and horizontal positioned, naturally volatilize solvent, solidify 10min in 60 ℃ of baking ovens, separate paper promptly on the cooling bonnet.
Claims (10)
1. beta-Asarone transdermal plaster by comprising that bin-storing layer, backing layer, adhesive layer and protective layer form, is characterized in that bin-storing layer contains the beta-Asarone of 0.1%～40% (mass percent) and acceptable substrate pharmaceutically.
2. the described beta-Asarone transdermal plaster of claim 1 is characterized in that bin-storing layer is the viscose decentralized.
3. claim 1 or 2 described beta-Asarone transdermal plasters is characterized in that beta-Asarone content is 5～25% (mass percents) in the bin-storing layer.
4. claim 1 or 2 described beta-Asarone transdermal plasters is characterized in that the bin-storing layer mesostroma is one or more the mixture among methylcellulose (MC-Na), sodium carboxymethyl cellulose (CMC-Na), polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, tragakanta, EUDRAGIT (You Teqi) E12.5.
5. claim 1 or 2 described beta-Asarone transdermal plasters is characterized in that the bin-storing layer mesostroma is one or more the mixture among ethyl cellulose (EC), carboxy-propyl cellulose (HPC), EUDRAGIT (You Teqi) E100.
6. claim 1 or 2 described beta-Asarone transdermal plasters is characterized in that bin-storing layer contains antiseptic, and antiseptic is wherein one or more mixture of benzoic acid, sodium benzoate, parabens, and consumption is 0.01%～0.3%.
7. claim 1 or 2 described beta-Asarone transdermal plasters, it is characterized in that bin-storing layer contains Percutaneous absorption enhancer, Percutaneous absorption enhancer is wherein one or more mixture of azone, menthol, Tweens, dimethyl sulfoxide, succinic acid, and consumption is 0.015%～5%.
8. claim 1 or 2 described beta-Asarone transdermal plasters, wherein adhesive is wherein one or more mixture of polyisobutylene class pressure sensitive adhesive, acrylic compounds pressure sensitive adhesive, silicone rubber pressure sensitive adhesive, EUDRAGIT (You Teqi) E12.5, EUDRAGIT (You Teqi) E100.
9. claim 1 or 2 described beta-Asarone transdermal plasters, wherein the adhesive layer contains plasticizer, and plasticizer is wherein one or more mixture of kieselguhr, Kaolin, Pulvis Talci, zinc oxide.
10. claim 1 or 2 described beta-Asarone transdermal plasters, wherein backing layer be non-woven fabrics, elastic force adhesive plaster, polyethylene film, polypropylene screen, polychloroethylene film, aluminum plastic film, aluminium foil, scribble layer of silicone aluminium foil, scribble silicone aluminium foil, scribble polyester and silicone aluminium foil wherein a kind of.
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| CNB2005100350805A CN100336504C (en) | 2005-06-13 | 2005-06-13 | Beta-Asarone transdermal plaster |
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| CNB2005100350805A CN100336504C (en) | 2005-06-13 | 2005-06-13 | Beta-Asarone transdermal plaster |
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| CN1720908A true CN1720908A (en) | 2006-01-18 |
| CN100336504C CN100336504C (en) | 2007-09-12 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849927A (en) * | 2010-06-13 | 2010-10-06 | 浙江大学 | Hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone and preparation method thereof |
| CN106074459A (en) * | 2016-07-11 | 2016-11-09 | 雷春生 | A kind of lasting water-retaining type hydrogel plaster supports the preparation method of layer material |
| CN113504158A (en) * | 2021-07-14 | 2021-10-15 | 山东诺明康药物研究院有限公司 | In-vitro transdermal test method for medicament containing boron dermatitis |
| CN117064866A (en) * | 2023-07-10 | 2023-11-17 | 北京丰科睿泰医药科技有限公司 | Burisperidone long-acting transdermal patch and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1067264C (en) * | 1998-04-10 | 2001-06-20 | 段玉新 | Medicinal patch for treatment of cough and asthma |
| CN1337222A (en) * | 2000-08-07 | 2002-02-27 | 雷学军 | Tooth-whitening tooth powder containing natural medicine |
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2005
- 2005-06-13 CN CNB2005100350805A patent/CN100336504C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849927A (en) * | 2010-06-13 | 2010-10-06 | 浙江大学 | Hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone and preparation method thereof |
| CN101849927B (en) * | 2010-06-13 | 2012-03-28 | 浙江大学 | Hot-melt pressure-sensitive adhesive transdermal patch containing alpha-asarone and preparation method thereof |
| CN106074459A (en) * | 2016-07-11 | 2016-11-09 | 雷春生 | A kind of lasting water-retaining type hydrogel plaster supports the preparation method of layer material |
| CN113504158A (en) * | 2021-07-14 | 2021-10-15 | 山东诺明康药物研究院有限公司 | In-vitro transdermal test method for medicament containing boron dermatitis |
| CN117064866A (en) * | 2023-07-10 | 2023-11-17 | 北京丰科睿泰医药科技有限公司 | Burisperidone long-acting transdermal patch and preparation method thereof |
| CN117064866B (en) * | 2023-07-10 | 2024-04-19 | 北京丰科睿泰医药科技有限公司 | Burisperidone long-acting transdermal patch and preparation method thereof |
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| CN100336504C (en) | 2007-09-12 |
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