CN104840973B - Escitalopram transdermal skin patches and preparation method thereof - Google Patents
Escitalopram transdermal skin patches and preparation method thereof Download PDFInfo
- Publication number
- CN104840973B CN104840973B CN201510220730.7A CN201510220730A CN104840973B CN 104840973 B CN104840973 B CN 104840973B CN 201510220730 A CN201510220730 A CN 201510220730A CN 104840973 B CN104840973 B CN 104840973B
- Authority
- CN
- China
- Prior art keywords
- escitalopram
- sensitive adhesive
- ion
- acid
- skin patches
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The invention belongs to pharmaceutical technology field, is related to escitalopram transdermal skin patches and preparation method thereof.The escitalopram transdermal skin patches are carried medicine pressure-sensitive adhesive layer and adherent layer are formed by back sheet；Carrying medicine pressure-sensitive adhesive layer includes escitalopram free alkali or its organic acid ion to compound, pressure sensitive adhesive, transdermal absorption accelerator.Wherein escitalopram free alkali or its organic acid ion account for the total dose of compound 2.0 20wt% for carrying medicine pressure-sensitive adhesive layer gross weight, and pressure sensitive adhesive accounts for 77 97wt% of gross weight, and transdermal absorption accelerator dosage accounts for 0 6.8wt% of gross weight.The escitalopram organic acid ion is in compound, the ratio of escitalopram free alkali and different organic acids is 0.5:1‑2:1.Escitalopram organic acid ion provided by the invention is to compound percutaneous absorption patch compared with escitalopram free alkali percutaneous absorption patch, it is possible to provide up to the insoluble drug release of the approximately constant speed of 7 days, patient medication compliance is greatly improved.
Description
Technical field：
The invention belongs to pharmaceutical technology field, is related to escitalopram transdermal skin patches and preparation method thereof.
Background technology：
As rhythm of life is constantly accelerated, the stress of people also gradually increases, and depression is as modern society
Common disease, high morbidity, its incidence quickly rise, it is contemplated that to the year two thousand twenty, it, which is likely to become, is only second to cardiopathic second
Big disease.Depression is a kind of using affective disorders as main types of presentation, and low notable and lasting mental state is main
The syndrome of feature, is mainly shown as depressed, speech reduction, spirit, bradykinesia, or even the symptom such as suicide attempts.
Current antidepressant medicine is broadly divided into following several：Monoamine oxidase inhibitors, tricyclic antidepressant, 5-HT
Reuptaking inhibitor and norepinephrine reuptake inhibitors.Wherein first two due to side effect it is larger, using having been limited
System, and the clinical practice of 5-HT reuptaking inhibitors is most extensive.Common 5-HT reuptaking inhibitors have 5 kinds:Prozac, Paro
Xi Ting, Sertraline, Fluvoxamine, Citalopram, are called " Five Golden Flowers " of 5-HT reuptaking inhibitors.
Escitalopram is called " the 6th golden flower ", the U.S. FDA of in August, 2002 approval of 5-HT reuptaking inhibitors
Listing, is the levo-enantiomer of racemic Citalopram, and it acts as 100 times of the effect of Citalopram dextrorotatory antipode.Its is right
The selectivity of 5-HT is stronger, Small side effects, is the first-line drug of current treatment depression.The related physics and chemistry ginseng of escitalopram
Number is as follows：Relative molecular mass 324g/mol, Determination of oil-water partition coefficient 3.5, pKa 9.6.
Escitalopram is mainly clinically peroral dosage form, and the treatment of depression generally requires long-term administration, for a long time
Gastrointestinal reaction, such as Nausea and vomiting, loss of appetite occurs in oral escitalopram.Some patients are because side effect is tight
Treatment is interrupted again, has seriously affected the performance of drug effect.Therefore, exploitation one kind can maintain effective dose for a long time while can also
The escitalopram novel form for improving patient compliance is of great significance.
Korean Patent KR20120022368 discloses a kind of transdermal drug delivery system of escitalopram.It is described transdermal to give
Medicine system is that escitalopram is scattered in pressure sensitive adhesive, and attaching 24h can realize constant release on the skin for design.And
KR20100063320 disclose a kind of Citalopram transdermal administration plaster containing high molecular polymer delay Citalopram into
Enter systemic blood circulation and the skin plaster agent of 72h is made.
For the patient with depression, it is necessary to which blood concentration can be maintained 3 days cutaneous penetrations to a couple of days by design
System.Such transdermal drug delivery system requirement uses the medicine of high relative contents.But if in traditional transdermal drug delivery system
The middle content for improving escitalopram, the initial release rate of medicine can be very big, and because dosage exhaustion is through speed after long-time
Rate very little.In addition, purpose in order to control escitalopram rate of release and add high molecular polymer or using release-controlled film
Method, its production technology become complicated and difficult, cost higher, and phenomenon of burst release occurs in transdermal formulation.
The defects of in order to overcome the prior art, the present invention combine escitalopram physicochemical property, by its with pharmaceutically
Acceptable organic acid combines to form escitalopram organic acid ion to compound, using this compound as curative effect medicine
Obtained escitalopram transdermal patch, can provide the insoluble drug release up to the approximately constant speed of 7 days.
The content of the invention：
It is an object of the invention to provide simple in structure, irritation is small, curative effect it is persistently gentle contain escitalopram
Week effect patch and preparation method thereof.
The present invention is achieved through the following technical solutions：
Escitalopram and the ion-pair complexes of different organic acids are synthesized first, are dissociated with substituting escitalopram
Alkali, so as to control the percutaneous transmission rates of escitalopram, realizes the slow constant release of 7 days.Afterwards, using chemically assisting in
Agent increases the Percutaneous permeability of escitalopram.
Escitalopram transdermal skin patches of the present invention are carried medicine pressure-sensitive adhesive layer and adherent layer are formed by back sheet；Carry
Medicine pressure-sensitive adhesive layer includes escitalopram free alkali or its organic acid ion to compound, pressure sensitive adhesive, transdermal absorption accelerator.
Wherein escitalopram free alkali or its organic acid ion account for the total dose of compound the 2.0- for carrying medicine pressure-sensitive adhesive layer gross weight
20wt%, pressure sensitive adhesive account for the 77-97wt% of gross weight, and transdermal absorption accelerator dosage accounts for the 0-6.8wt% of gross weight, preferably 1.9-
4.6wt%.Wherein escitalopram organic acid ion in compound, escitalopram free alkali and different organic acids
Molar ratio is 0.5:1-2:1, preferred proportion 1:1.
The escitalopram organic acid ion is pharmaceutically acceptable organic for escitalopram to compound
Ion pair complex, be oxalic acid escitalopram ion-pair complexes, maleic acid escitalopram ion-pair complexes,
Fumaric acid escitalopram ion-pair complexes, adipic acid escitalopram ion-pair complexes, benzoic acid Ai Sixi phthaleins
Pulan ion-pair complexes, salicylic acid escitalopram ion-pair complexes, p-aminobenzoic acid escitalopram ion
To the one or more in compound, benzene sulfonic acid escitalopram ion-pair complexes, preferably salicylic acid escitalopram
Ion-pair complexes and p-aminobenzoic acid escitalopram ion-pair complexes.
In order to improve the Percutaneous permeability of medicine, the transdermal absorption accelerator of addition includes alcohols, sulfoxide type, surface-active
Agent class, terpenes, amine, amide-type, aliphatic acid and esters, amino acids and its esters or phospholipids compounds, such as sapn
80th, Tween 80, span 20, azone, oleic acid, menthol, 1-methyl-2-pyrrolidinone, isopropyl myristate, will select above-mentioned rush
Into the one or more in agent, wherein it is preferred that isopropyl myristate.
Escitalopram free alkali is prepared via a method which：Oxalic acid Ai Sixi phthaleins are titrated with sodium hydrate aqueous solution
The aqueous solution of Pulan, extracts it to there is no oily liquids generation, then with suitable single or mixed organic solvents, takes off
Evaporation of organic solvent is drying to obtain after water.Organic solvent used can be aliphatic alcohols, ethers, alkanes, alkyl halide hydro carbons and
Fatty acid ester.Wherein preferred alkanes, alkyl halide hydro carbons and fatty acid ester.Specifically, organic solvent can be：Just oneself
Alkane, petroleum ether, atoleine, chloroform, 1,2- dichloroethanes, normal heptane, ethyl acetate, three fourth Methyl ethers, isopropyl acetate,
Methyl ethyl ketone, dimethyl sulfoxide, methyl isopropyl ketone, methyltetrahydrofuran and propyl acetate.
The escitalopram organic acid ion synthesizes compound by the following method：
(1) escitalopram free alkali is dissolved in acetone；
(2) it is proportionally added into organic acid；
(3) after when room temperature uniform stirring 2 is small, solvent evaporated, obtains target product.
Host material selected by pressure sensitive adhesive is silicone, polyisobutene class, according to esters of acrylic acid or cellulose family and he
Derivative in one or more, wherein it is preferred that the pressure-sensitive acrylate of hydroxyl, its dosage are 77-97wt%.
Further, carrying can also add in inert filler, plasticizer, tackifier or antioxidant in medicine pressure-sensitive adhesive layer
One or more, every dosage is respectively 1-10wt%.
Material selected by back sheet is aluminumpolyethylene composite membrane, polyesters composite membrane, polyurethane film, polyethylene individual layer
Film, polyolefin single film, ethylene vinyl acetate films or elastic non-woven cloth.
Material selected by adherent layer is surface through silicone oil release treatment or fluorine-containing polyester film or paper, fluoropolymer coating
Polyester film release film and polyester fluoropolymer coating polyester film release film.
The preparation process of patch of the present invention is:The organic acid ion of escitalopram is dissolved in compound organic molten
In agent, transdermal enhancer is added after being completely dissolved, or adds suitable inert filler, tackifier and antioxidant etc. again, and
It is scattered in the pressure sensitive adhesive of certain mass, rear transfer coated is sufficiently stirred in adherent layer, through 40-80 DEG C of dry 5-20min, backing
Layer covering, be punched into a certain size, specification, that is, escitalopram percutaneous absorption patch is made.Carrying medicine pressure sensitive adhesive thickness can be with
For 30-100 μm.
The escitalopram transdermal patch of the present invention effectively have adjusted the warp of escitalopram using ion pair strategy
Skin transmission rates, escitalopram can be discharged in the time of 1 week with uniform speed, so that curative effect more long lasting and stable；
The preparation agent of this patch is technically simple, patch adhesiveness is good, easy to use.
Embodiment：
The present invention is explained by following example in more detail, it should be apparent that：The present invention is not limited to embodiment, or only
Show as embodiment.
The preparation of 1 escitalopram free alkali of embodiment
2g oxalic acid escitaloprams are dissolved in 20ml distilled water, 4% (W/V) sodium hydrate aqueous solution is added dropwise to not
There is oily liquids generation again.With 3 extractions of 240ml ethyl acetate point, combining extraction liquid, adds suitable anhydrous sodium sulfate and carries out
Dehydration, then rotary evaporation is drying to obtain escitalopram free alkali.
Embodiment 2
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol maleic acids under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to maleic acid escitalopram ion-pair complexes.
Embodiment 3
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol fumaric acid under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to fumaric acid escitalopram ion-pair complexes.
Embodiment 4
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol adipic acids under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to adipic acid escitalopram ion-pair complexes.
Embodiment 5
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol benzoic acid under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to benzoic acid escitalopram ion-pair complexes.
Embodiment 6
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol p-aminophenyls under agitation
Formic acid, continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to p-aminobenzoic acid escitalopram ion-pair complexes.
Embodiment 7
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol salicylic acids under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to salicylic acid escitalopram ion-pair complexes.
Embodiment 8
0.1mol escitalopram free alkalis are dissolved in 40ml acetone, add 0.1mol benzene sulfonic acids under agitation,
Continue stirring 2 it is small when, rotary evaporation volatilizes solvent up to benzene sulfonic acid escitalopram ion-pair complexes.
Embodiment 9
0.6mmol escitalopram free alkalis are scattered in 2g pressure-sensitive acrylates DT-4098 and are sufficiently mixed,
It is spread evenly across on adherent layer, by 50 DEG C of dry 15min, is then covered with the back lining materials for including PVC or non-woven fabrics, punching
Cut, the patch that thickness is 30 μm is made.
Embodiment 10
0.6mmol oxalic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-4098
In be sufficiently mixed, be spread evenly across on adherent layer, by 50 DEG C of dry 15min, then with the backing materials for including PVC or non-woven fabrics
Material covering, punching, is made the patch that thickness is 30 μm.
Embodiment 11
0.6mmol maleic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
Embodiment 12
0.6mmol fumaric acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
Embodiment 13
0.6mmol adipic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
Embodiment 14
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-4098, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
Embodiment 15
0.6mmol benzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
Embodiment 16
0.6mmol salicylic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
Embodiment 17
0.6mmol benzene sulfonic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates DT-
It is sufficiently mixed, is spread evenly across on adherent layer in 4098, by 50 DEG C of dry 15min, then with the back of the body for including PVC or non-woven fabrics
Lining material covers, punching, and the patch that thickness is 30 μm is made.
In-vitro percutaneous experiment：
20% (W/V) urethane of the male rabbit of 1.5Kg or so is anaesthetized, cuts off belly wool, then use electric shaver
Carefully remaining hair is shaved totally, auricular vein injects air and puts to death rabbit, peels off skin, removes subcutaneous fat, uses physiology salt
Water is rinsed well to be in store for after -70 DEG C.
Percutaneous absorbtion experiment is carried out using horizontal dual chamber diffusion cell, effective diffusion area is 0.95cm2, acceptance pool volume
3ml, acceptable solution are the phosphate buffer of pH7.4.Patch is pasted on keratoderma, is fixed in acceptance pool, fixed point takes
Sample 2ml, supplements 2ml blank acceptable solutions.Continuing magnetic force stirs during experiment, and mixing speed 600-800rpm, uses periphery
The temperature of circulator bath maintenance system is 32 DEG C.
1 organic acid of table to percutaneous drug absorption speed in escitalopram percutaneous absorption patch influence (Mean ±
S.D.) (n=4)
Conclusion：After escitalopram forms ion-pair complexes with organic acid, the warp of escitalopram can be regulated and controled
Skin transmission rates, its mesoxalic acid, fumaric acid, maleic acid, the binary ion pair complex of adipic acid and benzene sulfonic acid ion pair are answered
The percutaneous transmission rates of compound are too low, do not reach the effective blood drug concentration of escitalopram；Benzoate to compound and
Free alkali is the same with the extension of time, rate reduction；Salicylic acid and p-aminobenzoic acid ion-pair complexes can make Ai Si
The percutaneous transmission rates of Citalopram kept constant speed and suitable amount at 7 days.
Embodiment 18
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-9301, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
Embodiment 19
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-2287, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
Embodiment 20
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-2516, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
Embodiment 21
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-2677, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
Embodiment 22
0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes are scattered in 2g pressure-sensitive acrylates
It is sufficiently mixed, is spread evenly across on adherent layer in DT-2852, by 50 DEG C of dry 15min, then using includes PVC or non-woven fabrics
Back lining materials covering, punching, it is 30 μm of patch that thickness, which is made,.
2 p-aminobenzoic acid escitalopram ion-pair complexes of table, 7 days Percutaneous permeabilities in different pressure sensitive adhesives
(Mean ± S.D.) (n=4)
Conclusion：The Percutaneous permeability highest of pressure sensitive adhesive without functional group, is secondly the pressure sensitive adhesive of hydroxy functional groups, containing carboxylic
The pressure sensitive adhesive Percutaneous permeability of base functional group is minimum.Therefore the it is preferred that pressure sensitive adhesive without functional group.
Embodiment 23
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g azones, are scattered in 2g acrylic acid
It is sufficiently mixed, is spread evenly across on adherent layer in esters pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
Embodiment 24
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g oleic acid, is scattered in 2g acrylic acid
It is sufficiently mixed, is spread evenly across on adherent layer in esters pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
Embodiment 25
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g span 20s, are scattered in 2g propylene
It is sufficiently mixed, is spread evenly across on adherent layer in esters of gallic acid pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
Embodiment 26
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1gN- methyl pyrrolidones, disperse
It is sufficiently mixed, is spread evenly across on adherent layer in 2g pressure-sensitive acrylates DT-4098, by 50 DEG C of dry 15min, so
Covered afterwards with the back lining materials for including PVC or non-woven fabrics, punching, the patch that thickness is 30 μm is made.
Embodiment 27
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g sorbester p17s, are scattered in 2g propylene
It is sufficiently mixed, is spread evenly across on adherent layer in esters of gallic acid pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
Embodiment 28
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g Tween 80s, are scattered in 2g propylene
It is sufficiently mixed, is spread evenly across on adherent layer in esters of gallic acid pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
Embodiment 29
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g isopropyl myristates, disperse
It is sufficiently mixed, is spread evenly across on adherent layer in 2g pressure-sensitive acrylates DT-4098, by 50 DEG C of dry 15min, so
Covered afterwards with the back lining materials for including PVC or non-woven fabrics, punching, the patch that thickness is 30 μm is made.
Embodiment 30
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.1g menthols, are scattered in 2g propylene
It is sufficiently mixed, is spread evenly across on adherent layer in esters of gallic acid pressure sensitive adhesive DT-4098, by 50 DEG C of dry 15min, then with includes
The back lining materials of PVC or non-woven fabrics cover, punching, and the patch that thickness is 30 μm is made.
The different accelerating agents of table 3 accumulate medicine in p-aminobenzoic acid escitalopram ion-pair complexes patch for 7 days
The influence (Mean ± S.D.) (n=4) of transit dose
Conclusion：Compared with without accelerating agent group, accelerating agent oleic acid, 1-methyl-2-pyrrolidinone, sorbester p17, Tween 80, peppermint
Alcohol does not significantly improve Percutaneous permeability.Azone significantly improves transmission rates with span 20, makes medicine in patch several in 3d
Release.Only isopropyl myristate can improve the Percutaneous permeability of 7d and maintain constant release.
Embodiment 31
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.05g isopropyl myristates, divide
Dissipate and be sufficiently mixed in 2g pressure-sensitive acrylates DT-4098, is spread evenly across on adherent layer, by 50 DEG C of dry 15min,
Then covered with the back lining materials for including PVC or non-woven fabrics, punching, the patch that thickness is 30 μm is made.
Embodiment 32
By 0.6mmol p-aminobenzoic acid escitalopram ion-pair complexes, 0.15g isopropyl myristates, divide
Dissipate and be sufficiently mixed in 2g pressure-sensitive acrylates DT-4098, is spread evenly across on adherent layer, by 50 DEG C of dry 15min,
Then covered with the back lining materials for including PVC or non-woven fabrics, punching, the patch that thickness is 30 μm is made.
3 different content isopropyl myristate of table is in p-aminobenzoic acid escitalopram ion-pair complexes patch
The influence (Mean ± S.D.) (n=4) of 7 days Percutaneous permeabilities of medicine
Conclusion：The isopropyl myristate of 0.1g is remarkably improved escitalopram Percutaneous permeability, is further added by Pork and beans
It is constant that the amount of cool isopropyl propionate promotees saturating effect.Therefore the dosage of isopropyl myristate accounts for the 0-6.8wt% of total amount, preferably 1.9-
4.6wt%.
Claims (12)
1. escitalopram transdermal skin patches, are made of, it is characterised in that carry medicine back sheet, load medicine pressure-sensitive adhesive layer and adherent layer
Pressure-sensitive adhesive layer includes escitalopram free alkali or its organic acid ion to compound, pressure sensitive adhesive, transdermal absorption accelerator, its
Middle escitalopram free alkali or its organic acid ion account for the total dose of compound the 2.0- for carrying medicine pressure-sensitive adhesive layer gross weight
20wt%, pressure sensitive adhesive account for the 77-97wt% of gross weight, and transdermal absorption accelerator dosage accounts for the 0-6.8wt% of gross weight, the Chinese mugwort
This Citalopram organic acid ion is the pharmaceutically acceptable organic acid ion of escitalopram to compound to compound, choosing
From benzoic acid escitalopram ion-pair complexes, salicylic acid escitalopram ion-pair complexes, p-aminobenzoic acid
One or more in escitalopram ion-pair complexes, the pressure sensitive adhesive are third without carboxyl and hydroxy functional group
Olefin(e) acid esters pressure sensitive adhesive.
2. escitalopram transdermal skin patches according to claim 1, it is characterised in that：The escitalopram has
Machine ion pair complex is prepared for escitalopram free alkali and organic acid reaction, escitalopram free alkali with it is organic
The ratio of acid is 0.5:1-2:1.
3. escitalopram transdermal skin patches according to claim 2, it is characterised in that：Escitalopram free alkali with
The ratio of organic acid is 1:1.
4. according to the escitalopram transdermal skin patches described in claim 1-3 any one, it is characterised in that：Described is percutaneous
Sorbefacient includes alcohols, sulfoxide type, surfactant-based, terpenes, amine, amide-type, aliphatic acid and esters, amino acid
Class and its esters or phospholipids compounds, dosage 1.9-4.6wt%.
5. the escitalopram transdermal skin patches according to any one of right 1-3, it is characterised in that：The percutaneous suction
Receipts accelerating agent is isopropyl myristate.
6. the escitalopram transdermal skin patches according to right 4, it is characterised in that：The transdermal absorption accelerator is meat
Isopropyl myristate.
7. escitalopram transdermal skin patches according to claim 1, it is characterised in that the escitalopram trip
It is prepared via a method which from alkali：The aqueous solution of oxalic acid escitalopram is titrated with sodium hydrate aqueous solution, to there is no
Oily liquids produces, then it is extracted with suitable single or mixed organic solvents, and evaporation of organic solvent is dried after dehydration
To obtain the final product, the organic solvent is aliphatic alcohols, ethers, alkanes, alkyl halide hydro carbons and fatty acid ester.
8. escitalopram transdermal skin patches according to claim 7, it is characterised in that the organic solvent is alkane
Class, alkyl halide hydro carbons and fatty acid ester.
9. escitalopram transdermal skin patches according to claim 8, it is characterised in that the organic solvent is aliphatic acid
Esters.
10. escitalopram transdermal skin patches according to claim 1, it is characterised in that the escitalopram
Organic acid ion synthesizes compound by the following method：
(1) escitalopram free alkali is dissolved in acetone；
(2) it is proportionally added into organic acid；
(3) after when room temperature uniform stirring 2 is small, solvent evaporated, to obtain the final product.
11. escitalopram transdermal skin patches according to claim 1, it is characterised in that：The load medicine pressure-sensitive adhesive layer
In be additionally added one or more in inert filler, plasticizer, tackifier or antioxidant, every dosage is respectively 1-
10wt%.
12. the preparation method of escitalopram transdermal skin patches according to claim 1, it is characterised in that：By Ai Sixi
The organic acid ion of phthalein Pulan is dissolved in organic solvent compound, and transdermal absorption accelerator is added after being completely dissolved, or
Suitable inert filler, tackifier and antioxidant are added again, and is scattered in the pressure sensitive adhesive of certain mass, are turned after being sufficiently stirred
Shifting is coated on adherent layer, through 40-80 DEG C of dry 5-20min, back sheet covering, be punched into a certain size, specification, that is, Ai Si is made
Citalopram percutaneous absorption patch.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510220730.7A CN104840973B (en) | 2015-05-04 | 2015-05-04 | Escitalopram transdermal skin patches and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510220730.7A CN104840973B (en) | 2015-05-04 | 2015-05-04 | Escitalopram transdermal skin patches and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104840973A CN104840973A (en) | 2015-08-19 |
| CN104840973B true CN104840973B (en) | 2018-04-17 |
Family
ID=53841212
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510220730.7A Active CN104840973B (en) | 2015-05-04 | 2015-05-04 | Escitalopram transdermal skin patches and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104840973B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108498491A (en) * | 2018-06-26 | 2018-09-07 | 沈阳药科大学 | A kind of transdermal oxybutynin absorption patch and its preparation and application |
| CN110638792B (en) * | 2019-10-16 | 2022-04-19 | 沈阳药科大学 | Rotigotine percutaneous absorption patch and preparation and application thereof |
| CN113171359B (en) * | 2021-05-08 | 2022-11-01 | 沈阳药科大学 | Chuangbuterol transdermal patch and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006001877A2 (en) * | 2004-04-13 | 2006-01-05 | Myriad Genetics, Inc. | Combination treatment for neurodegenerative disorders comprising r-flurbiprofen |
| KR20120022368A (en) * | 2010-09-02 | 2012-03-12 | 대화제약 주식회사 | A transdermal composition of escitalopram |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050101666A1 (en) * | 2003-11-07 | 2005-05-12 | H. Lundbeck A/S | Method of treating premenstrual dysphoric disorder with escitalopram |
-
2015
- 2015-05-04 CN CN201510220730.7A patent/CN104840973B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006001877A2 (en) * | 2004-04-13 | 2006-01-05 | Myriad Genetics, Inc. | Combination treatment for neurodegenerative disorders comprising r-flurbiprofen |
| KR20120022368A (en) * | 2010-09-02 | 2012-03-12 | 대화제약 주식회사 | A transdermal composition of escitalopram |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104840973A (en) | 2015-08-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2242971C2 (en) | Percutaneous therapeutic system containing neutralized acrylate-based adhesive substances gluing at pressing | |
| EP1030660B1 (en) | A transdermal drug delivery system for anti-inflammatory analgesic agent comprising diclofenac diethylammonium salt, and the manufacturing method thereof | |
| CN1232389A (en) | Patch | |
| CN104840973B (en) | Escitalopram transdermal skin patches and preparation method thereof | |
| MX2012011355A (en) | Transdermal delivery patch. | |
| CN111615381B (en) | Pharmaceutical composition for transdermal administration in the form of a hydrogel patch | |
| CN102946873A (en) | Transdermal absorption preparation | |
| JP5702489B2 (en) | Water-containing patch | |
| CN102413821A (en) | Transdermal preparation | |
| CN106267218A (en) | 4 terpinol aliphatic ester derivatives and application thereof and preparation method | |
| WO1996011710A1 (en) | External preparation for nail ringworm | |
| CN102283820B (en) | Granisetron transdermal patch and preparation method thereof | |
| CN102048717A (en) | Stable rasagiline composition | |
| CN102526001B (en) | Indomethacin salt transdermal patch and preparation method thereof | |
| JP4705343B2 (en) | Base for percutaneous absorption preparation and skin patch preparation using the same | |
| CN105147642A (en) | Transdermal patch containing formoterol or fumarate thereof | |
| CN101612141A (en) | Buprenorphine patch | |
| WO2014104149A1 (en) | Preparation for application to skin | |
| CN104069505A (en) | Percutaneous-absorption palonosetron patch and preparation method thereof | |
| CN107311865A (en) | Eugenol aliphatic ester derivatives and its application and preparation method | |
| CN113181141A (en) | Flurbiprofen gel plaster and preparation method thereof | |
| CN113171359B (en) | Chuangbuterol transdermal patch and preparation method thereof | |
| WO2008045461A2 (en) | Transdermal diethylstilbestrol for treating prostate cancer | |
| CN102018671A (en) | Estradiol transdermal spray and preparation method thereof | |
| CN101199476B (en) | Pennogenyl Saponins percutaneous-absorping preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |