CN102078619B - Transdermal therapeutic preparation - Google Patents
Transdermal therapeutic preparation Download PDFInfo
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- CN102078619B CN102078619B CN201010565511XA CN201010565511A CN102078619B CN 102078619 B CN102078619 B CN 102078619B CN 201010565511X A CN201010565511X A CN 201010565511XA CN 201010565511 A CN201010565511 A CN 201010565511A CN 102078619 B CN102078619 B CN 102078619B
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- ketotifen fumarate
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Abstract
The invention provides an application of tri(hydroxymethyl) methyl amine and a moisture absorbing packing material. In a patch of ketotifen fumarate provided with an adhering agent layer on a supporting body, the tri(hydroxymethyl) methyl amine and the moisture absorbing packing material are used for improving the content stability of the ketotifen fumarate and inhibiting the xanthochromia.
Description
The application is to be on April 20th, 2005 applying date, and application number is 200580049505.6, and denomination of invention is divided an application for the one Chinese patent application of " transdermal formulation ".
Technical field
The present invention relates to a kind of transdermal formulation, it contains ketotifen fumarate (Ketotifen fumarate) as effective ingredient, and the Percutaneously absorbable of effective ingredient is good, the medicament contg in the preparation through the time stable, and can suppress xanthochromia.Say in further detail; The present invention relates to a kind of transdermal formulation; Said transdermal formulation is on supporter, adhesive phase to be set and in the patch that forms; In this adhesive phase, except containing ketotifen fumarate, also contain specific alkaline matter, and this patch is packaged in the hygroscopicity packaging material and forms.
Background technology
4-(1-methyl-4-piperidylidene)-4H-benzo [4,5] cycloheptane [1,2-b] thiophene-10 (9H)-ketone (below, be called ketotifen.) and salt, anti-allergic effects and antihistamine effect with wide scope, known effective to tracheal branches asthma, allergic rhinitis, eczema, dermatitis, urticaria, skin pruritus, oculopathy etc.
In addition, contain the preparation of above-mentioned ketotifen, can use various doses of shapes such as tablet, capsule, syrup, unguentum, gel, eye drop as effective ingredient.Wherein, oral agents such as tablet, capsule, syrup, the drug effect persistence is excellent, but finds to exist the problem of side effect such as being prone to drowsiness, gastrointestinal disorders, liver obstacle.On the other hand,, be difficult to fixedly use amount and spreading area etc. about unguentum and gel, thus lack the required quantitative property of whole body therapeutic, in addition, exist coating part be clamminess, attached to the problem on the clothes.And then, about eye drop,, taken out of by tear easily though quick-acting is excellent, there is the problem that lacks the drug effect persistence.In contrast, patch can make a certain amount of medicament of skin absorbs, and be difficult to occur mistake and drink, forget the problem of taking medicine, and then, when finding side effect, as long as peel off, so be the high agent shape of serviceability at once.
Will be as the ketotifen fumarate of the salt of fumaric acid and ketotifen during through administration by percutaneous absorption, through adding alkaline matter, can make ketotifen free, improve skin permeability as free alkali.Yet, known as the ketotifen of free alkali though the skin permeability is good, in the time of in adding patch to, become dissolved state, through the time chemical content reduce, so lack stable content property, in addition, also find to occur xanthochromia.
In order to improve the stable content property of ketotifen fumarate; Known in the therapeutic agent in department of dermatologry fields such as dermatitis, eczema; Add bisulfites, sulphite, pyrosulfite, dibenzylatiooluene antioxidants such as (BHT) (for example, with reference to patent documentation 1.)。But, though find sodium sulfite to stable content property with to suppress xanthochromia effective, strong impulse property stink is arranged, and from BHT to skin irritant angle, have safety issue.
In addition, in order to make patch through also keeping stable status over a long time, the packaging material that form with the laminations such as aluminium foil of the moisture from the outside capable of blocking, oxygen, light etc. are usually packed.But for containing the patch of ketotifen fumarate, promptly use such packaging material to pack as effective ingredient, the ketotifen content stability that can not improve, and can not suppress xanthochromia.
Patent documentation 1: the spy opens flat 6-48935 communique
Summary of the invention
The present invention accomplishes under such situation, and its technical task that will solve is, to containing the patch of ketotifen fumarate as effective ingredient, improves the Percutaneously absorbable and the stable content property of medicament simultaneously, and suppresses its painted (xanthochromia).
The inventor etc. are in order to solve above-mentioned problem, have carried out various researchs to containing ketotifen fumarate as the patch of effective ingredient, and the result finds, through in adhesive phase, add three (methylol) aminomethane (below, note is made Tris.), and be packaged in the hygroscopicity packaging material, can improve the Percutaneously absorbable of medicament, chemical content become through the time stable, and can suppress xanthochromia.Find that in addition adding propyl gallate, using SIS is that binding agent base and rosin ester are to remove oxygen in fact tackifying resin and the atmosphere in packaging material, can further improve stable content property and suppress the xanthochromia effect, thereby accomplished the present invention.
Therefore, the present invention relates to
A kind of transdermal formulation is on supporter, adhesive phase to be set and the patch that forms, it is characterized in that this adhesive phase contains ketotifen fumarate and three (methylol) aminomethane, and patch is packaged in the hygroscopicity packaging material and forms.
Preferred version of the present invention is,
Above-mentioned transdermal formulation is characterized in that, above-mentioned adhesive phase further contains the propyl gallate of 0.01～10 weight %.
Above-mentioned transdermal formulation is characterized in that, above-mentioned adhesive phase is that binding agent base and rosin ester are that tackifying resin forms by SIS.
Above-mentioned transdermal formulation is characterized in that, above-mentioned adhesive phase is that binding agent base and rosin ester are that tackifying resin forms by SIS, and further contains the propyl gallate of 0.01～10 weight %.
And,
Above-mentioned transdermal formulation is characterized in that, above-mentioned packaging material have deoxygenation function, or above-mentioned packaging material be the non-permeability of oxygen and pack with deoxidizer, or inner with the above-mentioned packaging material of nitrogen replacement.
According to the present invention; To containing as effective ingredient in the patch of ketotifen fumarate; Special three (methylol) aminomethane of selecting adds from multiple alkaline matter; And then patch is packaged in the hygroscopicity packaging material, the Percutaneously absorbable and the stable content property of medicament can be improved simultaneously thus, and xanthochromia can be suppressed.And then, be that binding agent base and rosin ester are the adhesive phase that forms of tackifying resin and/or the atmosphere in the packaging material are waited with nitrogen replacement remove oxygen in fact through adding propyl gallate, using by SIS, can further improve above-mentioned effect.
The specific embodiment
Patch in the transdermal formulation of the present invention is provided with adhesive phase through binding agent and forms on supporter, this adhesive phase contains neccessary composition ketotifen fumarate and three (methylol) aminomethane, and other additives that add as required.In addition, use preceding purposes such as adhesive phase, can on adhesive phase, further be provided with and peel off surface layer from protection.
As above-mentioned binding agent, use under the room temperature to show the fusible binding agent of pressure-sensitive, for example can enumerate out, acrylic adhesive, rubber are binding agent and siloxane-based binding agent.Wherein, preferred acrylic adhesive and rubber are binding agent.Rubber is binding agent, owing to can freely select tackifying resin and other additives, so preferred especially.
As above-mentioned rubber is binding agent; For example can enumerate out; With natural rubber (suitable-1; The 4-isoprene), rubber-like elastic bodies such as synthetic rubber (anti--1,4-isoprene), SIS (SIS), polyisobutylene, polybutene, polyisoprene are as the binding agent of binding agent base.In these binding agent bases, add the tackifying resins such as petroleum line resin, alkyl-phenol resin, xylene resin of Colophonium, rosin derivative terpene resins such as rosin series resin, australene, nopinene such as (hydride, disproportionation thing, polymer, carboxylates etc.), terpene phenolic resin, fatty family, fragrant family, alicyclic ring family and copolymerization system, processing rubber is binding agent.Wherein, use SIS, and to use rosin ester be resin as the rubber of tackifying resin is binding agent as the binding agent base, from stable content property with suppress xanthochromic viewpoint, preferred especially.At this moment, rosin ester is the addition of tackifying resin, is that the binding agent base is a benchmark with styrene-isoprene-phenylethene, preferred 2～50 weight %.
In above-mentioned binding agent, as required, can add antioxidants such as filler, bisulfites, sulphite, pyrosulfite, propyl gallate such as liquid polybutene, liquid polyisobutylene, mineral wet goods softening agent, titanium oxide, zinc oxide etc.Wherein, the interpolation of propyl gallate, for improving stable content property and suppressing xanthochromia, particularly useful.The addition of propyl gallate if height goes beyond the scope, then brings bad influence to adhesive properties in the scope of 0.01～10 weight %, in addition, if be lower than this scope, it is low then to suppress the xanthochromia effect.
Transdermal formulation of the present invention contains the ketotifen fumarate as effective ingredient in above-mentioned adhesive phase.Its content is generally 0.1～30 weight %, is preferably 0.3～20 weight %.If content is higher than this scope, then ketotifen fumarate crystallization is sometimes separated out, and bonding force reduces, and in addition, if be lower than this scope, then is difficult to continue to obtain sufficient drug effect.
And then transdermal formulation of the present invention in above-mentioned adhesive phase, except containing ketotifen fumarate, also contains three (methylol) aminomethane (Tris).As alkaline matter that use always for the effective ingredient that makes the salt form in the preparation is free; Can enumerate out a lot of chemical compounds such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, sodium carbonate, sodium bicarbonate, phosphate, borate, acetate, ammonia, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine (DIPA).Yet wherein, sodium carbonate, sodium bicarbonate, phosphate etc. are insoluble in organic solvent, so be not suitable in the binding agent of solvent system, using.In addition, though potassium hydroxide and sodium hydroxide are solvable in alcohol, but add in the binding agent of solvent system, but because hygroscopy is high, and easy and carbon dioxide in air reaction, so be difficult to operation.And then, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine (DIPA) etc., sometimes after neutralization reaction because of oxygen, heat, light etc. can cause xanthochromia, promote the preparation xanthochromia sometimes.
In contrast, the Tris that uses among the present invention is the low crystal material of hygroscopicity, to light and thermally stable, so handle easily.When particularly adding in the adhesive phase, can improve the skin permeability of ketotifen fumarate with ketotifen fumarate, and remarkable inhibitory preparation xanthochromia.The addition of Tris is a benchmark with the ketotifen fumarate, is generally 20～100 weight %, is preferably 25～70 weight %.If addition is higher than this scope, then cause skin irritation sometimes, in addition,, then can not get the advantages of good skin permeability if be lower than this scope.Tris can directly add in the binding agent with crystallization or pulverulence, also can the Tris of crystallization or pulverulence be dissolved or be dispersed in the suitable organic solvent, then gained solution or dispersion liquid is added in the binding agent.
Transdermal formulation of the present invention for the percutaneous that promotes ketotifen fumarate absorbs, as required, can add transdermal absorption accelerator in above-mentioned adhesive phase.Among the present invention, transdermal absorption accelerator not only can promote the percutaneous of medicine to absorb, and can promote the skin of medicine to see through, and sees through promoter so be also referred to as skin sometimes.As this transdermal absorption accelerator; For example can enumerate out; Aliphatic alcohol, fatty acid, fatty acid ester, polyol alkyl ether, polyoxyethylene alkyl ether, glyceride (fatty acid ester of glycerol), polyhydric alcohol medium chain fatty acid ester, lactic acid alkyl ester, alkyl dicarboxylate, acylated amino, pyrrolidinone compounds etc., but do not limit these.These transdermal absorption accelerators can use separately, also can make up use more than 2 kinds.
As above-mentioned aliphatic alcohol, the saturated or unsaturated higher alcohol of carbon numbers 12 to 22 such as preferred oleyl alcohol, lauryl alcohol.
As above-mentioned fatty acid, can enumerate out linoleic acid, oleic acid, linolenic acid, stearic acid, isostearic acid and Palmic acid.
As above-mentioned fatty acid ester, can enumerate out isopropyl myristate, diisopropyl adipate and isopropyl palmitate.
As above-mentioned polyol alkyl ether; For example can enumerate out; The alkyl ether of polyhydric alcohol such as glycerol, ethylene glycol, propylene glycol, 1,3 butylene glycol, two glycerol, polyglycereol, diethylene glycol, Polyethylene Glycol, dipropylene glycol, polypropylene glycol, anhydrosorbitol, Sorbitol, methyl glucoside, oligosaccharide, reduction oligosaccharide.The carbon number of the moieties of the alkyl ether of polyhydric alcohol is preferably 6～20.
As above-mentioned polyoxyethylene alkyl ether, the carbon number of preferred alkyl part is 6～20, and the repetitive (O-CH of polyoxyethylene chain
2CH
2-) number be 1～9.Can enumerate out polyoxyethylene lauryl ether, Polyoxyethylene cetyl ether, polyoxyethylene stearyl base ether and polyoxyethylene oleyl ether particularly.
As above-mentioned glyceride, preferred carbon number is the glyceride of 6～18 fatty acid.Glyceride can be categorized into monoglyceride, diglyceride and triglyceride, but all can use according to its bonded fatty acid number, in addition, also can use their mixture, for example, and the mixture of monoglyceride and diglyceride.As the fatty acid that forms glyceride, can enumerate out sad, capric acid, dodecylic acid, tetradecanoic acid, hexadecanoic acid, octadecanoid acid (stearic acid) and oleic acid.
As other transdermal absorption accelerator, can enumerate out lactic acid, tartaric acid, 1,2,6-hexane triol, benzylalcohol and lanoline.
Wherein, polyoxyethylene alkyl ether and their mixture more than 2 kinds such as fatty acid ester, polyoxyethylene oleyl ether such as fatty acids such as aliphatic higher alcohol, isostearic acid, isopropyl myristate, Palmic acid isopropyl alcohol ester such as preferred lauryl alcohol.Transdermal absorption accelerator uses 1～50 weight % usually, preferably uses 2～40 weight %.
As above-mentioned supporter, preferably do not adsorb the medicament in the adhesive phase, and from supporting the not supporter of release medicine of side.For example can enumerate out particularly, non-woven fabrics, weave cotton cloth, thin film or sheet, porous plastid, foaming body, paper and the complex that forms by their laminations.
Material as above-mentioned non-woven fabrics; Can enumerate out polyester based resin, artificial silk, polyamide, polyester ether, polyurethane, polyacrylic resin, polyvinyl alcohol, styrene-isoprene-styrene copolymer-and styrene-ethylene-propylene-styrene copolymers such as the polyolefin-based resins of polyethylene, polypropylene etc., PETG, polybutylene terephthalate (PBT), PEN.
As above-mentioned material of weaving cotton cloth, can enumerate out cotton, artificial silk, polyacrylic resin, polyester based resin and polyvinyl alcohol.
Material as above-mentioned thin film or sheet; For example can enumerate out polyester based resin, cellophane, polyvinyl alcohol, ethylene-vinyl alcohol copolymer, polrvinyl chloride, polystyrene, polyurethane, polyacrylonitrile, fluororesin, styrene-isoprene-styrene copolymer-, SBR styrene butadiene rubbers, polybutadiene, vinyl-vinyl acetate copolymer, polyamide and polysulfones such as polyacrylic resin, PETG, polybutylene terephthalate (PBT), PEN such as polyolefin-based resins such as polyethylene, polypropylene, polymethyl methacrylate, polyethyl methacrylate.
As above-mentioned paper, for example can enumerate out impregnation paper, coated paper, fine paper, kraft paper and paper, cellophane and synthetic paper.
As above-mentioned complex, can enumerate out, at the complex of above-mentioned non-woven fabrics or above-mentioned thin film of the superimposed layer of weaving cotton cloth or sheet.
Patch in the transdermal formulation of the present invention can pass through rubbing method, hot melt, rolling process etc., the adhesive phase that is formed by above-mentioned binding agent is set on above-mentioned supporter prepares.
In the above-mentioned rubbing method, for example, the organic solution that will contain ketotifen fumarate, Tris and other additives and binding agent is coated on supporter or peels off on the surface layer, makes its drying, makes patch.As the solvent of this organic solution, can enumerate out toluene, ethyl acetate and hexane.
In above-mentioned hot melt, for example, with adhesive ingredients heated and stirred under nitrogen replacement; Fusion reduces temperature then, adds ketotifen fumarate, Tris and other additives afterwards; Carrying out homogeneous mixes; This mixture is being peeled off on the surface layer through the extension of heat seeling coating machine, and the lamination supporter prepares patch thus then.
In above-mentioned rolling process, for example, independent mixing binding agent base, temperature then descends; Add tackifying resin afterwards, and then carry out mixingly, temperature is descended, add softening agent then; Carry out mixingly, add ketotifen fumarate, Tris and other additives at last, carry out mixing; The mixture extension of gained is being peeled off on the surface layer, and the lamination supporter prepares patch thus then.
Temperature conditions in these method for preparinies and mixing time etc. can be according to the appropriate changes such as cooperation prescription of binding agent.In addition, the thickness of adhesive phase is generally 10～300 μ m.
Above-mentioned rubbing method when needs make ketotifen fumarate be soluble in the binding agent, can use the dissolving adjuvant as required.For example can enumerate out the fatty acid ester of crotonocyl toluidines (Crotamiton), ethanol, carbamide, propylene glycol, 1-menthol, Herba Menthae wet goods particularly.The dissolving adjuvant can use separately, or combination is used more than 2 kinds.In addition, dissolution aids uses 0～40 weight % usually, preferably uses the amount of 0～20 weight %.
In above-mentioned hot melt or above-mentioned rolling process, the mixture that will contain various compositions and binding agent usually extends and is peeling off on the surface layer, but also can this mixture be extended on supporter as required, peels off surface layer as the coating agent lamination.
That uses among the present invention has hygroscopic packaging material; For example can enumerate out; Contain the hygroscopicity packaging material of hygroscopic matter, in non-poisture-penetrability packaging material, taken in the packaging material of hygroscopic agent; But, preferably use the hygroscopicity packaging material owing to exist the volume that increases preparation to drink problems such as hygroscopic agent with mistake.In addition,, further preferably have the packaging material of light-proofness, in addition,, further preferably have the packaging material of heat sealability from the viewpoint of packaging operation from stable content property and the xanthochromic viewpoint of inhibition.
Above-mentioned packaging material for example can be enumerated out, the packaging material of heat sealability resin bed more than a kind that formed by polyethylene, polypropylene, polyethylene vinylacetate etc. at metal forming superimposed layers such as aluminum.In addition, in the outside of aluminium foil or other metal formings, further lamination polyester, cellophane, paper etc.
Transdermal formulation of the present invention is packed above-mentioned patch through above-mentioned hygroscopic agent packaging material and is formed, and preferably makes the inner atmosphere of packaging material after the packing not contain oxygen in fact.From this atmosphere, remove oxygen, can give packaging material self deoxidizing capacity, or in the packaging material of the non-permeability of oxygen, take in deoxidizer through for example, or carry out with the atmosphere in the nitrogen replacement packaging material.Thus, can further improve stable content property and suppress the xanthochromia effect.
Below, come to explain particularly the present invention based on embodiment, but the present invention does not receive any restriction of these embodiment.Below, short of special instruction, " % " refers to " quality % ".
Embodiment 1
In the composition shown in the table 1; With SIS is the binding agent base: Network イ Application タ Star Network 3570C (Japanese ゼ オ Application Co., Ltd. system); Rosin ester is a tackifying resin: パ イ Application Network リ ス タ Le KE311 (Arakawa Chemical Industries, Ltd.'s system) and isopropyl palmitate are dissolved in the toluene; In this solution, add ketotifen fumarate and Tris, obtain binding agent.Is that 40 μ m that kind are coated on the thick PET thin film of 75 μ m that silicon handled with this binding agent with its dried thickness, 110 ℃ dry 3 minutes down, adhesive phase is set.Then, at the thick PET thin film of adhesive phase superimposed layer 25 μ m.The patch that obtains like this is packaged in the hygroscopicity packaging material (ト one ヤ Le De ラ イ (trade name), Japan ア Le ミ ニ ウ system Co., Ltd. system), obtains transdermal formulation of the present invention.
Embodiment 2
Except with the atmosphere in nitrogen replacement (replacement rate is more than the 70%) packaging material, other and embodiment 1 operate equally, obtain transdermal formulation of the present invention.
Embodiment 3
Except in binding agent, further adding the solution (methanol/toluene=1/9) of 10% propyl gallate, other and embodiment 1 operate equally, obtain transdermal formulation of the present invention.
Embodiment 4
Except with the atmosphere in nitrogen replacement (replacement rate is more than the 70%) packaging material, other and embodiment 3 operate equally, obtain transdermal formulation of the present invention.
Comparative example 1
As alkaline matter, use monoethanolamine to replace Tris, add dibenzylatiooluene (BHT) as antioxidant, in addition, pack without the hygroscopicity packaging material, in addition, other and embodiment 1 operate equally, obtain the transdermal formulation of comparative example.
Comparative example 2
Except as tackifying resin, use the terpenic series tackifying resin: in addition, operate equally, obtains the transdermal formulation of comparative example by other and comparative example 1 for YS レ ジ Application PX-1150N (ヤ ス Ha ラ ケ ミ カ Le Co., Ltd. system).
Comparative example 3
Except as tackifying resin, using alicyclic oil is tackifying resin: ア Le コ Application P-100 (Arakawa Chemical Industries, Ltd.'s system) in addition, other and comparative example 1 are operated equally, obtain the transdermal formulation of comparative example.
Comparative example 4
In not being packaged in the hygroscopicity packaging material, other and embodiment 1 operate equally, obtain the transdermal formulation of comparative example.
Comparative example 5
In not being packaged in the hygroscopicity packaging material, other and embodiment 3 operate equally, obtain the transdermal formulation of comparative example.
Comparative example 6
As alkaline matter, use monoethanolamine to replace Tris, add dibenzylatiooluene as antioxidant, in addition, other and embodiment 2 operate equally, obtain the transdermal formulation of comparative example.
Table 1: the having or not of the composition of binding agent (weight %) and hygroscopicity packaging material and nitrogen replacement
Tackifying resin 1: パ イ Application Network リ ス タ Le KE311 (Arakawa Chemical Industries, Ltd.'s system)
Tackifying resin 2:YS レ ジ Application PX-1150N (ヤ ス Ha ラ ケ ミ カ Le Co., Ltd. system)
Tackifying resin 3: ア Le コ Application P-100 (Arakawa Chemical Industries, Ltd.'s system)
To each transdermal formulation of embodiment 1～4 and comparative example 1～6, estimate 40 ℃ with relative humidity 75% condition under after through 6 months stable content property with suppress xanthochromia.
Stable content property is the concentration through ketotifen fumarate in the liquid chromatogram measuring patch, with ratio (%) expression of the concentration (initial value) in the patch after intact with respect to firm manufacturing.Will be with respect to initial value, being assessed as of residual ketotifen fumarate more than 95% " zero " is more than 90% and less than 95% be assessed as " △ ", be evaluated as " * " less than 90%.
Suppress xanthochromia, can pass through the form and aspect that color computer (ス ガ testing machine Co., Ltd. system) is measured patch, with Δ YI value (through the time after YI value-firm manufacturing after the YI value) represent.Δ YI value is less than 30 be assessed as " zero ", being assessed as more than 30 " * ".
The result is shown in table 2.
Table 2: result of the test
Can know from the result of table 2, transdermal formulation of the present invention, through the time chemical content reduce and xanthochromia very little.Wherein, With the embodiment 2 of the atmosphere in the nitrogen replacement packaging material and the embodiment 3 that further adds propyl gallate; Stable content property and inhibition xanthochromia two Fang Jun carry out nitrogen replacement simultaneously and have shown best effect with the embodiment 4 that adds propyl gallate than embodiment 1 excellence.
Relative therewith, comparative example 1～3 owing to use monoethanolamine to replace Tris as alkaline matter, so lack stable content property, even it uses different tackifying resins, does not change yet.Yet if compare with the comparative example 3 of comparative example that uses the terpenic series tackifying resin 2 and alicyclic series tackifying resin, using rosin ester is the comparative example 1 stable content property excellence of tackifying resin.
In addition, do not use the comparative example 4 of hygroscopicity packaging material, though can fully suppress xanthochromia, stable content property existing problems even further add the comparative example 5 of propyl gallate, do not obtain satisfactory result yet.
And then, such shown in comparative example 6, promptly use hygroscopicity packaging material packing, and,, can not realize gratifying stable content property and suppress xanthochromia if do not use Tris as alkaline matter with the atmosphere in the nitrogen replacement packaging material.
Claims (5)
1. the application of (methylol) aminomethane and hygroscopicity packaging material; Be on supporter, to be provided with in the patch of ketotifen fumarate of adhesive phase; Stable content property and inhibition xanthochromia in order to improve ketotifen fumarate use three (methylol) aminomethanes and hygroscopicity packaging material.
2. application as claimed in claim 1 is characterized in that, above-mentioned hygroscopicity packaging material have deoxygenation function, or above-mentioned packaging material be the non-permeability of oxygen and pack with deoxidizer, or inner with the above-mentioned packaging material of nitrogen replacement.
3. application as claimed in claim 1 is characterized in that above-mentioned adhesive phase further contains the propyl gallate of 0.01～10 weight %.
4. application as claimed in claim 1 is characterized in that, above-mentioned adhesive phase is that binding agent base and rosin ester are that tackifying resin forms by SIS.
5. application as claimed in claim 1 is characterized in that, above-mentioned adhesive phase is that binding agent base and rosin ester are that tackifying resin forms by SIS, and further contains the propyl gallate of 0.01～10 weight %.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010565511XA CN102078619B (en) | 2005-04-20 | 2005-04-20 | Transdermal therapeutic preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010565511XA CN102078619B (en) | 2005-04-20 | 2005-04-20 | Transdermal therapeutic preparation |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005800495056A Division CN101166531A (en) | 2005-04-20 | 2005-04-20 | Medicinal preparation for percutaneous absorption |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102078619A CN102078619A (en) | 2011-06-01 |
| CN102078619B true CN102078619B (en) | 2012-11-14 |
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| CN201010565511XA Expired - Fee Related CN102078619B (en) | 2005-04-20 | 2005-04-20 | Transdermal therapeutic preparation |
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| CN106243096B (en) * | 2016-07-29 | 2019-11-29 | 上海璃道医药科技有限公司 | The new application of tricyclic drugs |
| CN116098877A (en) * | 2023-01-04 | 2023-05-12 | 新领医药技术(深圳)有限公司 | Stable rotigotine transdermal drug delivery kit, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1151863A (en) * | 1995-12-14 | 1997-06-18 | 姜钦治 | Mixed skin absorbent |
| EP1238664A1 (en) * | 1999-12-15 | 2002-09-11 | Hisamitsu Pharmaceutical Co. Inc. | Adhesive preparations |
-
2005
- 2005-04-20 CN CN201010565511XA patent/CN102078619B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1151863A (en) * | 1995-12-14 | 1997-06-18 | 姜钦治 | Mixed skin absorbent |
| EP1238664A1 (en) * | 1999-12-15 | 2002-09-11 | Hisamitsu Pharmaceutical Co. Inc. | Adhesive preparations |
Non-Patent Citations (3)
| Title |
|---|
| JP特开2004-175771A 2004.06.24 |
| JP特开平6-184000A 1994.07.05 |
| JP特开平8-143452A 1996.06.04 |
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