CN107929267A - Transdermal plaster of rivastigmine and preparation method thereof - Google Patents
Transdermal plaster of rivastigmine and preparation method thereof Download PDFInfo
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- CN107929267A CN107929267A CN201711249217.6A CN201711249217A CN107929267A CN 107929267 A CN107929267 A CN 107929267A CN 201711249217 A CN201711249217 A CN 201711249217A CN 107929267 A CN107929267 A CN 107929267A
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- sensitive adhesive
- pressure
- rivastigmine
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- transdermal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Emergency Medicine (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to pharmacy technical field, and in particular to a kind of transdermal plaster of rivastigmine and preparation method thereof；It is equipped between backing film and adherent layer and carries medicine pressure-sensitive adhesive layer, the load medicine pressure-sensitive adhesive layer includes active constituents of medicine and pressure sensitive adhesive matrix, and the part by weight of active constituents of medicine and pressure sensitive adhesive matrix is 2~4:5~7；The pressure sensitive adhesive matrix is any two kinds in the acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group and the acrylate pressure-sensitive adhesive without functional group according to 33:67~67:33 part by weight compounds to obtain；Transdermal plaster of rivastigmine stability provided by the invention is good, irritation is weak, transdermal release performance is good.
Description
Technical field
The invention belongs to pharmacy technical field, and in particular to a kind of transdermal plaster of rivastigmine and preparation method thereof.
Background technology
Alzheimer's disease (Alzheimer disease, AD) is commonly called as senile dementia, is a kind of serious central nervous system
System degenerative disorders.Its pathogenesis is probably the water of the hippocampus of patient, neopallium cholinacetyltranslase and acetylcholine
It is flat to substantially reduce, cortex cholinergic neuron mediator dysfunction.Its clinical manifestation mainly has memory disorders, cognitive disorder and essence
Refreshing behavior disorder.With the arrival of Chinese society's aging, elderly population number is increasing, and the old man for suffering from senile dementia is also increasingly
It is more.A variety of symptoms such as memory loss, retardation of thinking, behavior disorder have seriously affected the work of Alzheimer's
Work, family and social relationships.At present, Rivastigmine is the active drug for treating alzheimer's disease.
Rivastigmine, also known as profit cut down the bright of this, are a kind of carbamic acid class brain selectivity acetylcholinesteraseinhibitors inhibitors, its
The mechanism of action is by delaying degraded of the cholinergic neuron to acetylcholine to promote cholinergic nerve to conduct.At present, it is related
The formulation of Rivastigmine has capsule and transdermal patch, and due to Rivastigmine capsule, there are larger first pass effect and some stomaches
Enteron aisle adverse reaction, and be administered orally and patients of senile dementia is inconvenient, therefore transdermal patch is become as clinical practice
It is preferred.In the prior art, the wide variety of Rivastigmine patch, but all there are cold flow in varying degrees, production process
The shortcomings of complexity, skin permeation rates are low, and irritation is strong, and mechanics of system evaluation is not known and stability is poor.
The content of the invention
The primary and foremost purpose of the present invention is that providing the kappa that a kind of stability is good, irritation is weak, transdermal release performance is good draws
Spit of fland transdermal patch.
To achieve the above object, the technical solution adopted by the present invention is：
A kind of transdermal plaster of rivastigmine, is equipped between backing film and adherent layer and carries medicine pressure-sensitive adhesive layer, and the load medicine is pressure-sensitive
Glue-line includes active constituents of medicine and pressure sensitive adhesive matrix, and the part by weight of active constituents of medicine and pressure sensitive adhesive matrix is 2~4:5~
7；The pressure sensitive adhesive matrix for the acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group and
Any two kinds in acrylate pressure-sensitive adhesive without functional group are according to 33:67~67:33 part by weight compounds to obtain.
Experiment finds that Rivastigmine has preferable release property in the pressure-sensitive acrylate containing hydroxyl group
Can, but stability is poor；There is excellent release performance and stability in the pressure-sensitive acrylate containing carboxylic group,
But cohesive force is poor；Release performance and stability are poor in the pressure-sensitive acrylate without functional group.
The present invention mixes two kinds containing not isoplastic acrylate pressure-sensitive adhesive, and comprehensive respective advantage, Rivastigmine exists
There is the solubility more than 30%wt in obtained pressure sensitive adhesive matrix；Kappa required when percutaneously effectively treatment 24 is small can be carried
Draw spit of fland dosage, realize 24 it is small when effectively, stablize, be administered continuously；Found using transdermal test in vitro release experiment, continued through rat skin
24 accumulate infiltration capacity up to 2607 μ g/cm when small2, the transdermal penetration rates height of medicine；Obtained transdermal plaster of rivastigmine is 6
List is miscellaneous in a month accelerated stability test is below 0.20%, always miscellaneous to be less than 1%；Patch can keep good after sticking skin
Gas permeability and penetrability, therefore can effectively reduce the side effects such as the irritation of skin；Without cold flow during use, and patch mechanics
Performance is also preferable.
It is another object of the present invention to provide the low transdermal plaster of rivastigmine of a kind of simple production process, cost
Preparation method, includes the following steps：
(1) pressure sensitive adhesive matrix is prepared：Acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate containing hydroxyl group
Pressure sensitive adhesive, the acrylate pressure-sensitive adhesive without functional group are uniformly mixed；
(2) prepare and carry medicine pressure sensitive adhesive：Antioxidant is added into pressure sensitive adhesive matrix；Active constituents of medicine is dissolved with solvent, then
Add in pressure sensitive adhesive matrix；
(3) medicine pressure sensitive adhesive will be carried to be applied on adherent layer, it is 10-20 minutes dry at 65-75 DEG C；Then composite back lining form,
Suitable dimension is cut into, up to transdermal plaster of rivastigmine.
Rivastigmine first passes through solvent dissolving in advance, adds in pressure sensitive adhesive matrix, can so improve kappa in patch and draw
The uniformity in spit of fland, and be conducive to dissolving and release of the Rivastigmine in pressure sensitive adhesive matrix.
Brief description of the drawings
Fig. 1 is the In-vitro release curves figure of embodiment 1-8 and comparative example 1；
Fig. 2 is the transdermal test in vitro curve map of embodiment 1-8 and comparative example 1.
Embodiment
1-8 is further described technical solution disclosed by the invention with reference to embodiments.
Embodiment 1：The preparation of transdermal plaster of rivastigmine
(1) weighing the acrylate pressure-sensitive adhesive containing carboxylic group, (trade name is：Acrylate pressure-sensitive adhesive 235A)
5.26g, (trade name is the acrylate pressure-sensitive adhesive containing hydroxyl group：Acrylate pressure-sensitive adhesive 2510) 4.77g, mixing stirs
Mix uniformly, obtain pressure sensitive adhesive matrix；
(2) the vitamin E solution 2ml of 3mg/ml is added into pressure sensitive adhesive matrix, is stirred evenly；Weigh Rivastigmine
18mg, after being dissolved with solvent ethyl acetate, adds in pressure sensitive adhesive matrix, when stirring 2 is small, obtains carrying medicine pressure sensitive adhesive, when standing 1 is small
Remove bubble；
(3) medicine pressure sensitive adhesive will be carried to be applied on adherent layer, the thickness of the load medicine pressure-sensitive adhesive layer of formation is micro- for 25 micron -40
Rice, is administered area≤10 square centimeter；It is 10-20 minutes dry at 65-75 DEG C；Then composite back lining form, is cut into suitable dimension, i.e.,
Obtain transdermal plaster of rivastigmine.
Embodiment 2：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 1, unlike, the dosage of acrylate pressure-sensitive adhesive 235A is 3.51g, third
The dosage of olefin(e) acid ester pressure-sensitive 2510 is 6.91g, and the dosage of Rivastigmine is 19mg.
Embodiment 3：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 1, unlike, the dosage of acrylate pressure-sensitive adhesive 235A is 7.01g, third
The dosage of olefin(e) acid ester pressure-sensitive 2510 is 3.18g, and the dosage of Rivastigmine is 20mg.
Embodiment 4：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 1, unlike, pressure sensitive adhesive matrix is contained the third of carboxylic group by 5.26g
(trade name is olefin(e) acid ester pressure-sensitive：Acrylate pressure-sensitive adhesive 235A) and Acrylate pressure sensitives of the 5.18g without functional group
(trade name is glue：Acrylate pressure-sensitive adhesive 4098) mix.
Embodiment 5：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 4, unlike, the dosage of acrylate pressure-sensitive adhesive 235A is 3.51g, third
The dosage of olefin(e) acid ester pressure-sensitive 4098 is 6.91g；The dosage of Rivastigmine is 19mg.
Embodiment 6：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 4, unlike, the dosage of acrylate pressure-sensitive adhesive 235A is 7.01g, third
The dosage of olefin(e) acid ester pressure-sensitive 4098 is 3.45g；The dosage of Rivastigmine is 20mg.
Embodiment 7：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 1, unlike, pressure sensitive adhesive matrix is contained the third of hydroxyl group by 3.18g
(trade name is olefin(e) acid ester pressure-sensitive：Acrylate pressure-sensitive adhesive 2510) and Acrylate pressure sensitives of the 6.91g without functional group
(trade name is glue：Acrylate pressure-sensitive adhesive 4098) mix；The dosage of Rivastigmine is 19mg, in addition, it is dense to use 4ml instead
The dibutyl hydroxy toluene solution for 3mg/ml is spent as antioxidant.
Embodiment 8：The preparation of transdermal plaster of rivastigmine
Prepared using the method for embodiment 7, unlike, the dosage of acrylate pressure-sensitive adhesive 2510 is 6.36g, third
The dosage of olefin(e) acid ester pressure-sensitive 4098 is 3.45g；The dosage of Rivastigmine is 20mg.
It should be noted that during actually patch is prepared, it is solvent to select propane diols or n-butanol, selects butyl
Anisole or propylgallate can also obtain the same or similar technique effect for antioxidant, and the present invention is succinct event,
This is not enumerated.
Comparative example 1：Choose commercially available Rivastigmine transdermal patch is as comparative example, the trade name of the commercial product
EXELON, article No. 4546B, EXP JUL 2018, specification 9mg/5cm2And 18mg/10cm2。
Performance test：
First, stability test
Percutaneous plaster in embodiment 1-8 and comparative example 1 is put into temperature as 40 DEG C, relative humidity is 75% stability
In chamber, checked for impurities content, the results are shown in Table 1 after 6 months.
Table 1：Transdermal patch accelerates 6 months impurity contents
As shown in Table 1, obtained Rivastigmine patch is respectively provided with higher stability in embodiment 1-8.This explanation：Kappa
La Ting in the acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group, do not contain functional group
Any two kinds in the acrylate pressure-sensitive adhesive of group are respectively provided with higher stabilization in mixed pressure sensitive adhesive matrix in varing proportions
Property, meet national regulations.
2nd, mechanics evaluation is tested
(1) peeling force is tested：By the transdermal patch in embodiment 1-8 and comparative example 1,50mm × 100mm sizes are cut into,
It is attached at respectively on the clean stainless steel plate placed vertically, is rolled 3 times with the roller of 2kg is round-trip on each patch, after twenty minutes will
Patch upper end doubling, and hang 200g counterweights, inverts by gravity and peels off patch, when record patch is completely exfoliated required
Between, it the results are shown in Table 2.
(2) holding power is tested：By the transdermal patch in embodiment 1-8 and comparative example 1,50mm × 100mm sizes are cut into,
It is attached at respectively on the clean stainless steel plate placed vertically, is first rolled 3 times with the roller of 2kg is round-trip on each patch, then will
200g counterweights are hung on below patch, and lead is parallel with gravity direction, and record patch completely falls off the required time, as a result
It is shown in Table 2.
Table 2：Patch mechanics evaluation
| Patch | Holding power/min | Peeling force/s |
| Comparative example 1 | 43 | 98 |
| Embodiment 1 | 57 | 92 |
| Embodiment 2 | 72 | 88 |
| Embodiment 3 | 64 | 90 |
| Embodiment 4 | 87 | 128 |
| Embodiment 5 | 112 | 96 |
| Embodiment 6 | 67 | 87 |
| Embodiment 7 | 66 | 112 |
| Embodiment 8 | 62 | 96 |
As shown in Table 2：Obtained Rivastigmine patch is respectively provided with preferable mechanical property in embodiment 1-8.This explanation：Card
Ba Lating in the acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group, do not contain function
Any two kinds in the acrylate pressure-sensitive adhesive of group are respectively provided with preferable power in mixed pressure sensitive adhesive matrix in varing proportions
Performance is learned, specifically, holding power is superior to the patch in comparative example 1, the peeling force of patch is also excellent made from section Example
Patch in comparative example 1.
3rd, vitro release is tested
1st, instrument and reagent
Instrument：TK-12A percutaneous dispersion test instrument；2695/2998 high performance liquid chromatographs of Waterse.
Reagent：Physiological saline；Methanol (chromatographic grade, SIGAMA)；Disodium hydrogen phosphate, triethylamine (analysis is pure)；Liquor epinephrinae bitartratis ophthalmicus
Rivastigmine reference substance；(An Keyuliang minister in ancient times pharmaceutcal corporation, Ltd, lot number are respectively transdermal plaster of rivastigmine：20171001、
20171002、20171003、20171004、20171005、20171101、20171102、20171103)；Rivastigmine is transdermal
Patch (Novartis Co., Ltd, trade name EXELON, article No. 4546B, EXP JUL 2018).
2nd, method and result
The foundation of 2.1 vitro release experimental methods
Experimental provision uses improved Franz diffusing cells method, which is involuted by upper and lower two tubular glass tubes, folder
Dialysis membrane therebetween is divided into two Room by upper and lower, and upper chamber is diffuser casing, and lower room is receiving chamber, is connected with the side of receiving chamber
For sample introduction, sampling and the probe tube for excluding bubble.Diffusion cell volume is 6.5ml, and effective diffusion area is 2.2cm2.Take respectively
Patch in embodiment 1-8 and comparative example 1, is attached on dialysis membrane；Physiological saline is filled into receiving chamber, excludes bubble, water-bath
Temperature is 32 ± 0.2 DEG C, adds stirrer constant temperature to stir, rotating speed 300r/min.0.5,1,2,4,8 after experiment starts,
12,24h microsyringes sample 200 μ l from receiving chamber, while respectively add the physiological saline of 32 ± 0.2 DEG C of preheatings of same volume,
Physiological saline filtering in advance and ultrasonic degassing bubble.
Samples taken is respectively placed in 5ml volumetric flasks, adds methanol -0.05M disodium hydrogen phosphates-triethylamine (50：50：
0.02) scale is settled to, is shaken up, filters, takes subsequent filtrate as assay test solution.
Precision weighs liquor epinephrinae bitartratis ophthalmicus Rivastigmine reference substance 6.34mg, is placed in 10ml volumetric flasks, with methanol -0.05M phosphorus
Sour disodium hydrogen-triethylamine (50：50：0.02) scale is settled to, up to reference substance solution.
The foundation of Rivastigmine analysis method in 2.2 release in vitro liquid
Using Thermo ODSHYPERSIL chromatographic columns (5 μm of particle diameter, 4 × 250mm of size), with methanol -0.05M phosphoric acid hydrogen
Disodium-triethylamine (50：50：0.02) it is mobile phase；Detection wavelength is 214nm, and column temperature is room temperature (21~26 DEG C), and flow velocity is
1ml/min.Precision draws test solution and each 10 μ l of reference substance solution, is injected separately into high performance liquid chromatograph, measures, and
Calculate preparation (%).Mapped with preparation (%) to release time (t), draw In-vitro release curves, as a result such as
Shown in Fig. 1.
4th, Ligustrazine hydrochloride is tested
1st, instrument and reagent
Instrument：TK-12A type percutaneous dispersion test instrument；2695/2998 high performance liquid chromatographs of Waterse.
Reagent：Physiological saline；Methanol (chromatographic grade, SIGAMA)；Disodium hydrogen phosphate, triethylamine (analysis is pure)；Liquor epinephrinae bitartratis ophthalmicus
Rivastigmine reference substance；(An Keyuliang minister in ancient times pharmaceutcal corporation, Ltd, lot number are respectively transdermal plaster of rivastigmine：20171001、
20171002、20171003、20171004、20171005、20171101、20171102、20171103)；Rivastigmine is transdermal
Patch (Novartis Co., Ltd, trade name EXELON, article No. 4546B, EXP JUL 2018).
2nd, method and result
The foundation of 2.1 transdermal permeation in vitro methods
Experimental provision uses improved Franz diffusing cells method, which is involuted by upper and lower two tubular glass tubes, folder
Mouse skin therebetween is divided into two Room by upper and lower, and upper chamber is diffuser casing, and lower room is receiving chamber, mouse skin stratum corneum side towards diffuser casing,
It is connected with the side of receiving chamber for sample introduction, sampling and the probe tube for excluding bubble.Diffusion cell volume is 6.5ml, is effectively expanded
It is 2.2cm2 to dissipate area.Distinguish patch in Example 1-8 and comparative example 1, be attached in mouse skin stratum corneum side；Into receiving chamber
Physiological saline is filled, excludes bubble, bath temperature is 32 ± 0.2 DEG C, adds stirrer constant temperature to stir, rotating speed 300r/min.Point
0.5,1,2,4,8,12,24h microsyringe does not sample 200 μ l from receiving chamber after experiment starts, while respectively adds consubstantiality
The physiological saline of 32 ± 0.2 DEG C of preheatings of product, physiological saline filters in advance and ultrasonic degassing steeps.
Samples taken is respectively placed in 5ml volumetric flasks, adds methanol -0.05M disodium hydrogen phosphates-triethylamine (50：50：
0.02) scale is settled to, is shaken up, filters, takes subsequent filtrate as assay test solution.
Precision weighs liquor epinephrinae bitartratis ophthalmicus Rivastigmine reference substance 6.34mg, is placed in 10ml volumetric flasks, with methanol -0.05M phosphorus
Sour disodium hydrogen-triethylamine (50：50：0.02) scale is settled to, up to reference substance solution.
The foundation of Rivastigmine analysis method in 2.2 Cutaneous permeation liquid
Using Thermo ODSHYPERSIL chromatographic columns (5 μm of particle diameter, 4 × 250mm of size), with methanol -0.05M phosphoric acid hydrogen
Disodium-triethylamine (50：50：0.02) it is mobile phase；Detection wavelength is 214nm, and column temperature is room temperature (21~26 DEG C), and flow velocity is
1ml/min.Precision draws test solution and each 10 μ l of reference substance solution, is injected separately into high performance liquid chromatograph, measures, and
Calculate preparation (%).Mapped with preparation (%) to release time (t), draw transdermal test in vitro curve, as a result such as
Shown in Fig. 2.
From Fig. 1-2：Obtained Rivastigmine patch is respectively provided with good percutaneous release performance in embodiment 1-8.This
Explanation：Rivastigmine in the acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group, be free of
Have any two kinds in the acrylate pressure-sensitive adhesive of functional group be respectively provided with varing proportions in mixed pressure sensitive adhesive matrix it is good
Good percutaneous release performance.
5th, resistance to cold-flow test
Patch in Example 1-8 and comparative example 1, is attached separately in PET bags, and 40 DEG C of constant temperature preserve.Experiment starts 3 latter
At the time point of the moon and 6 months, take out the situation for visually confirming pressure sensitive adhesive matrix layer.
The result shows that：Flow deformation does not occur for the pressure sensitive adhesive matrix layer of patch in embodiment 1-8, does not observe that cold flow shows
As；And in contrast, the pressure sensitive adhesive matrix layer segment of patch is spilled over to the outside of patch in comparative example 1, bond, go out with packaging bag
Existing cold flow.
Claims (9)
1. a kind of transdermal plaster of rivastigmine, is equipped between backing film and adherent layer and carries medicine pressure-sensitive adhesive layer, the load medicine pressure sensitive adhesive
Layer includes active constituents of medicine and pressure sensitive adhesive matrix, and active constituents of medicine is Rivastigmine or its pharmaceutically acceptable salt, its
It is characterized in that：The part by weight of active constituents of medicine and pressure sensitive adhesive matrix is 2~4:5~7；The pressure sensitive adhesive matrix is to contain carboxylic
The acrylate pressure-sensitive adhesive of base group, the acrylate pressure-sensitive adhesive containing hydroxyl group, the acrylate pressure without functional group
Any two kinds in quick glue are according to 33:67~67:33 part by weight compounds to obtain.
2. transdermal plaster of rivastigmine according to claim 1, it is characterised in that：The acrylic acid containing carboxylic group
Ester pressure-sensitive is87-2074、87-235A、87-2353、87-2852、87-2051、87-2052、
87-2054、87-2194、87-2196、One in 87-2677
Kind or numerous compositions.
3. transdermal plaster of rivastigmine according to claim 1, it is characterised in that：The acrylic acid containing hydroxyl group
Ester pressure-sensitive is87-2510、87-2287、87-2516、87-2525、One or more compositions in 87-4287.
4. transdermal plaster of rivastigmine according to claim 1, it is characterised in that：The acrylic acid without functional group
Ester pressure-sensitive is87-9301、87-4098、87-6908、
GELVAOne or more compositions in 3083.
A kind of 5. preparation method of transdermal plaster of rivastigmine according to any one of claim 1-4, it is characterised in that
Include the following steps：
(1) acrylate pressure-sensitive adhesive containing carboxylic group, the acrylate pressure-sensitive adhesive containing hydroxyl group, without functional group
Acrylate pressure-sensitive adhesive be uniformly mixed, obtain pressure sensitive adhesive matrix；
(2) antioxidant is added into pressure sensitive adhesive matrix；Active constituents of medicine is dissolved with solvent, is added in pressure sensitive adhesive matrix, is obtained
To load medicine pressure sensitive adhesive；
(3) medicine pressure sensitive adhesive will be carried to be applied on adherent layer, it is 10-20 minutes dry at 65-75 DEG C；Then composite back lining form, is cut into
Suitable dimension, up to transdermal plaster of rivastigmine.
6. the preparation method of transdermal plaster of rivastigmine according to claim 5, it is characterised in that：The transdermal patch bag
Include the raw material of following weight fraction：Pressure sensitive adhesive matrix 50%-70%, active constituents of medicine 20%-40%, antioxidant 0.01-
0.1%th, the sum of solvent 5-25%, the percentage by weight of above raw material is 100%.
7. the preparation method of the transdermal plaster of rivastigmine according to claim 5 or 6, it is characterised in that：The solvent is
One or more compositions in ethyl acetate, propane diols, n-butanol.
8. the preparation method of the transdermal plaster of rivastigmine according to claim 5 or 6, it is characterised in that：The antioxidant
One or more compositions in butyl anisole, dibutyl hydroxy toluene, propylgallate, vitamin E etc..
9. the preparation method of transdermal plaster of rivastigmine according to claim 5, it is characterised in that：The Rivastigmine is saturating
The dosage of skin patch is 10-20mg；The thickness of the load medicine pressure-sensitive adhesive layer of formation is 30 microns -80 microns, and administration area≤10 are flat
Square centimetre.
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| CN201711249217.6A CN107929267A (en) | 2017-12-01 | 2017-12-01 | Transdermal plaster of rivastigmine and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926549A (en) * | 2018-09-27 | 2018-12-04 | 安徽安科余良卿药业有限公司 | Rivastigmine gel emplastrum and preparation method thereof |
| CN111195243A (en) * | 2018-11-16 | 2020-05-26 | 北京泰德制药股份有限公司 | Transdermal patch containing rivastigmine |
| CN113350318A (en) * | 2021-06-23 | 2021-09-07 | 烟台大学 | Skeleton type transdermal patch containing rivastigmine and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011118683A1 (en) * | 2010-03-25 | 2011-09-29 | 東洋化学株式会社 | Patch for medical use |
| CN104136025A (en) * | 2012-02-28 | 2014-11-05 | 日绊株式会社 | Adhesive skin patch |
| CN105997951A (en) * | 2016-06-12 | 2016-10-12 | 润和生物医药科技(汕头)有限公司 | Cutaneous penetration system containing rivastigmine and preparation method |
-
2017
- 2017-12-01 CN CN201711249217.6A patent/CN107929267A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011118683A1 (en) * | 2010-03-25 | 2011-09-29 | 東洋化学株式会社 | Patch for medical use |
| CN104136025A (en) * | 2012-02-28 | 2014-11-05 | 日绊株式会社 | Adhesive skin patch |
| CN105997951A (en) * | 2016-06-12 | 2016-10-12 | 润和生物医药科技(汕头)有限公司 | Cutaneous penetration system containing rivastigmine and preparation method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926549A (en) * | 2018-09-27 | 2018-12-04 | 安徽安科余良卿药业有限公司 | Rivastigmine gel emplastrum and preparation method thereof |
| CN111195243A (en) * | 2018-11-16 | 2020-05-26 | 北京泰德制药股份有限公司 | Transdermal patch containing rivastigmine |
| CN113350318A (en) * | 2021-06-23 | 2021-09-07 | 烟台大学 | Skeleton type transdermal patch containing rivastigmine and preparation method thereof |
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