CN113350318A - Skeleton type transdermal patch containing rivastigmine and preparation method thereof - Google Patents

Skeleton type transdermal patch containing rivastigmine and preparation method thereof Download PDF

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CN113350318A
CN113350318A CN202110699680.0A CN202110699680A CN113350318A CN 113350318 A CN113350318 A CN 113350318A CN 202110699680 A CN202110699680 A CN 202110699680A CN 113350318 A CN113350318 A CN 113350318A
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matrix
sensitive adhesive
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medicine
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由春娜
李铭安
张策
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Yantai University
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • 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
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

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  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention belongs to the field of pharmaceutical preparations, and provides a skeleton type transdermal patch containing rivastigmine and a preparation method thereof, wherein the patch comprises: the drug-containing layer is positioned above the protective layer, and the protective layer is positioned above the back lining layer; the active ingredient of the drug-containing layer is rivastigmine free alkali or pharmaceutically acceptable salt thereof, the rivastigmine transdermal patch disclosed by the invention effectively avoids gastrointestinal adverse reactions, can be continuously applied for 7 days, has good safety and continuous and stable transdermal effect, and greatly improves the drug compliance and convenience of patients.

Description

Skeleton type transdermal patch containing rivastigmine and preparation method thereof
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a skeleton type transdermal patch containing rivastigmine and a preparation method thereof.
Background
Dementia (dementias)ia) is a syndrome that is centered on impairment of acquired cognitive function and leads to a marked decline in the patient's ability to live daily, to learn, to work and to social interaction. Impairment of cognitive function in a patient involves the ability to remember, learn, orient, understand, judge, calculate, speak, visuospatial function, analyze and solve problems, often accompanied by mental, behavioral and personality abnormalities at some stage of the course of the disease. Alzheimer Disease (AD) is an age-related degenerative disease of the nervous system, the most common form of dementia. It is pathologically characterized by senile plaques, neurofibrillary tangles, hippocampal pyramidal cell granule vacuolization and neuronal loss. Clinically, the disease is characterized by insidious attack, continuous progression of symptoms, progressive cognitive decline and personality change. The disease course is usually 5-10 years. According to the report of the international Alzheimer's disease society, about 5000 million AD patients exist in the world, and the number of AD patients is estimated to rise to 1.52 hundred million people by 2050[1]. The incidence rate of AD of people over 50 years old in China is about 4.4 percent[2]。
Rivastigmine/rivastigmine is a second-generation cholinesterase inhibitor with a chemical name of (S) -N-ethyl-3- [ l- (dimethylamino) ethyl]-phenyl N-methylcarbamate, a pseudoirreversible carbamate AChEI with selective effect on the Central Nervous System (CNS), slowing down the degradation of acetylcholine by inhibiting acetylcholinesterase (AChE). In addition, rivastigmine can also inhibit butyrylcholinesterase (BuChE), and research shows that BuChE plays an important role in the pathogenesis of AD, so that rivastigmine can obviously improve the cognitive function of AD patients as the only AChE and BuChE dual inhibitor at present[5]。
Rivastigmine was developed and marketed by original Minohua in various dosage forms, including rivastigmine bitartrate capsules (a) containing rivastigmine as an active ingredient
Figure BDA0003129766560000011
Hard capsule 1.5mg, 3mg, 4.5mg and 6mg), rivastigmine bitartrate oral liquid (
Figure BDA0003129766560000012
Oral solution 2mg/mL),and a rivastigmine transdermal patch (4.6mg/24 hours, 9.5mg/24 hours, and 13.3mg/24 hours, one patch per day). Wherein the hard capsule (Rivastigmine bitartrate capsule)
Figure BDA0003129766560000013
1.5mg, 3mg, 6mg) and transdermal patch (rivastigmine transdermal patch)
Figure BDA0003129766560000014
4.6mg/24 hours, 9.5mg/24 hours) were marketed in china in 2015 and 2017, respectively. The transdermal patch improves the medication compliance of patients, is convenient to interrupt administration at any time, can avoid the first pass effect of oral administration in liver and the degradation of the medicament in gastrointestinal tract, and reduces the individual difference of medication; can keep the blood concentration stable in the effective treatment concentration, avoid the peak valley phenomenon of the blood concentration caused by oral administration and the like, and reduce the toxic and side effect. The incidence of adverse events, particularly nausea and vomiting, reported with rivastigmine transdermal patches is significantly lower than with oral formulations[6]. However, at present, the once-a-day rivastigmine transdermal patch and the imitation drug thereof are only marketed in the world, the transdermal patch needs to be replaced every day, and if the rivastigmine transdermal patch with longer service cycle such as once-a-week period can be developed, the medication compliance and the medication convenience of patients can be greatly improved, and the care burden of caregivers can be reduced.
Disclosure of Invention
The invention provides a rivastigmine transdermal patch and a preparation method thereof, the patch can be continuously applied for 1-7 days, has continuous and stable transdermal effect and good safety, and effectively improves the medication compliance and the medication convenience of patients.
The technical scheme of the invention is as follows:
a matrix-type transdermal patch containing rivastigmine, the patch comprising: the drug-containing layer is positioned above the protective layer, and the protective layer is positioned above the back lining layer;
the active ingredient of the drug-containing layer is rivastigmine free base, or a pharmaceutically acceptable salt thereof;
the drug-containing layer is composed of one or more of polyvinyl alcohol, cellulose acetate, acrylate pressure-sensitive adhesive containing carboxyl groups, acrylate pressure-sensitive adhesive containing hydroxyl groups, acrylate pressure-sensitive adhesive containing no functional groups, polybutylene pressure-sensitive adhesive, polysiloxane pressure-sensitive adhesive and natural rubber;
the medicine-containing layer also contains an antioxidant, and the antioxidant consists of one or more of butyl anisole, propyl gallate, tocopherol and dibutyl hydroxy toluene;
the protective layer is one of polyethylene, polystyrene, polypropylene and release paper treated by paraffin or dimethyl silicone oil separant.
Preferably, the controlled release film also comprises an adhesive layer and a controlled release film; the sticking layer is positioned below the protective layer, and the controlled release film is positioned below the sticking layer;
wherein, the controlled release membrane is one of an ethylene-vinyl acetate copolymer membrane, a polysiloxane membrane, a polypropylene membrane and a cellulose acetate membrane;
the adhesive layer is one or more of polyvinyl alcohol, cellulose acetate, acrylate pressure-sensitive adhesive containing carboxyl groups, acrylate pressure-sensitive adhesive containing hydroxyl groups, acrylate pressure-sensitive adhesive containing no functional groups, polybutylene pressure-sensitive adhesive, polysiloxane pressure-sensitive adhesive and natural rubber.
Preferably, the method comprises the following steps:
firstly, preparing a medicine-containing layer matrix, and adding an antioxidant into the medicine-containing layer matrix after the matrix is uniformly mixed; dissolving active ingredients with solvent, and adding into drug-loaded matrix containing drug layer; coating the medicine carrying matrix on the protective layer, drying, compounding a backing film, and cutting into a proper size.
Preferably, the method comprises the following steps: firstly, preparing a medicine-containing layer matrix, and adding an antioxidant into the medicine-containing layer matrix after the matrix is uniformly mixed; dissolving active ingredients with solvent, and adding into drug-loaded matrix containing drug layer; coating the medicine-carrying matrix on the protective layer, and compounding a backing film after drying; preparing an adhesive layer, adding a solvent into the material of the adhesive layer, uniformly mixing, coating the mixture on the other side of the protective layer, drying at 40-80 ℃, compounding the controlled release film on the adhesive layer after drying, removing the protective layer, compounding the drug-containing layer and the adhesive layer, and cutting into a proper area to obtain the controlled release film.
Has the advantages that:
the rivastigmine transdermal patch disclosed by the invention effectively avoids gastrointestinal adverse reactions, can be continuously applied for 7 days, has good safety and continuous and stable transdermal effect, and greatly improves the medication compliance and convenience of patients.
Drawings
FIG. 1 shows examples (examples 1 to 3) of the present invention and commercially available products
Figure BDA0003129766560000031
In vitro transdermal flux comparison plots;
Detailed Description
The technical solutions disclosed in the present invention are further illustrated below with reference to examples, but the present invention is not limited thereto.
The backing layer of the present invention may be polyvinyl chloride, polyethylene, aluminum foil, polypropylene, polyester, polyethylene terephthalate, aluminum foil, non-woven fabric, etc.
Example 1
The transdermal patch described in this example consists of a backing layer, a protective layer, and a drug-containing layer.
Components Function of Dosage (g)
Rivastigmine API 8
Acrylate pressure-sensitive adhesive containing carboxyl group Adhesive agent 40
Acrylate pressure-sensitive adhesive Adhesive agent 18
Propyl gallate Antioxidant agent 0.1
Ethyl acetate Solvent(s) Proper amount of
Non-woven fabric Backing layer Proper amount of
Siliconized paper Protective layer Proper amount of
The preparation process comprises the following steps: taking the acrylic ester pressure-sensitive adhesive containing carboxyl groups and the acrylic ester pressure-sensitive adhesive according to the prescription amount, uniformly mixing the acrylic ester pressure-sensitive adhesive and the acrylic ester pressure-sensitive adhesive by using ethyl acetate, adding rivastigmine and tocopherol dissolved by the ethyl acetate, uniformly mixing the mixture, coating the mixture on a protective layer, controlling the thickness, drying the mixture at 40-60 ℃, compounding the mixture with a back lining layer, and cutting the mixture into a proper area to obtain the acrylic ester pressure-sensitive adhesive.
Example 2
The transdermal patch described in this example consists of a backing layer, a drug-containing layer, an adhesive layer, and a protective layer.
Components Function of Composition/amount (g)
Rivastigmine API 14
Silicone pressure sensitive adhesive Adhesive for drug-containing layer 29
Tocopherol Antioxidant agent 0.02
Polybutylene Adhesive layer 14
Ethyl acetate Solvent(s) Proper amount of
N-hexane Solvent(s) Proper amount of
Aluminum foil Backing layer Proper amount of
Polystyrene Protective layer Proper amount of
The preparation process comprises the following steps:
1. preparing a medicine-containing layer: taking silicone pressure-sensitive adhesive according to the prescription amount, adding rivastigmine and tocopherol dissolved by ethyl acetate, uniformly mixing, coating on the middle protective layer, controlling the thickness, and drying at 40-60 ℃.
2. Preparing an adhesive layer: and adding the polybutene pressure sensitive adhesive in the prescription amount into n-hexane, uniformly mixing, coating on the protective layer, and drying at 40-80 ℃.
3. Removing the middle protective layer of the medicated layer, compounding the medicated layer on the adhesive layer, and cutting into suitable area.
Example 3
The transdermal patch described in this example consists of a backing layer, a drug-containing layer, a controlled release membrane, an adhesive layer, and a protective layer.
Components Function of Composition/amount (g)
Rivastigmine API 11
Polysiloxane pressure-sensitive adhesive Adhesive agent 30
Butyl anisole Antioxidant agent 0.09
Polyacrylate pressure-sensitive adhesive Adhesive layer 24
Ethyl acetate Solvent(s) Proper amount of
Eucalyptol Solvent(s) Proper amount of
Ethylene-vinyl acetate copolymer film Controlled release film Proper amount of
Polyvinyl chloride Backing layer Proper amount of
Siliconized polystyrene Protective layer Proper amount of
The preparation process comprises the following steps:
1. preparing a medicine-containing layer: taking polysiloxane pressure-sensitive adhesive according to the prescription amount, adding rivastigmine and tocopherol dissolved by ethyl acetate, uniformly mixing, coating on the middle protective layer, controlling the thickness, and drying at 40-60 ℃.
2. Preparing an adhesive layer: and adding the polyacrylate pressure-sensitive adhesive in the prescription amount into the cineole, uniformly mixing, coating the mixture on the protective layer, drying at 40-80 ℃, and compounding the controlled release film on the adhesive layer after drying.
3. Removing the protective layer of the medicine-containing layer, compounding the medicine-containing layer and the adhesive layer, and cutting into appropriate area.
Test 1: skin irritation test
The method comprises the following steps of randomly dividing 6 rabbits into two groups (3 rabbits each), namely a complete skin group and a damaged skin group, carrying out local unhairing treatment on the back 24 hours before a test, and adopting a same-body self-contrast method, wherein the proximal end is a complete skin area and the proximal end is a damaged skin area. The test article (example 2) and the control blank patch were applied to the test area and the control area on the back of the rabbit, respectively, for 7 days each time for 14 days, the application site was cleaned with warm water after removal of the patch, and the patch was applied again after 1 h. Before the first administration, 1h after each cleaning and 24h, 48h and 72h after the last administration of the cleaning medicament, whether the applied part has erythema and edema and the recovery condition and time of the change are observed, and the stimulation evaluation intensity of the test object is evaluated according to the evaluation result.
Experiments show that the product has good general conditions and weight increase in administration process and observation period. The intact skin area, with no edema in the test and control areas, showed mild erythema in one animal on day 14 and resolved 24h after withdrawal, with the average scores in the test and control areas being 0 and 0.05, respectively, and evaluated as non-irritating according to the skin irritation intensity evaluation criteria. For the damaged skin area, the mild erythema appears after the first application of most animals in the test area and the control area, the natural performance of the damaged wound healing is probably realized, the damaged area is completely healed after 7 days of the test, the average score of the damaged skin test area and the average score of the damaged skin control area are both less than 0.35 in the administration process and the observation period, and the stimulation intensity is nonirritant. Therefore, the rivastigmine transdermal patch and the blank patch are continuously applied to the intact skin and the damaged skin of the rabbit for 14 days, and the skin irritation strength is nonirritant.
Test 2: skin allergy test
30 healthy guinea pigs were divided into 3 groups, and divided into a risperidone transdermal patch test group, a blank patch group, and a positive control group by a random equilibrium method, each group consisting of 10 positive patches, each of which was half male and female, the patch of example 2 (risperidone transdermal patch test group), the blank patch (blank patch group), and 0.2mL (positive control group) of 1% ethanol solution of 2, 4-dinitrochlorobenzene as a positive sensitizer were applied to the unhairing zone on the back side before administration, and the sensitization was performed 3 times on days 0, 7, and 14 as an induction period. Stopping the drug for 14 days after the last sensitization in the induction period, exciting the hair-removed area on the other side of the back of the animal on the 14 th day after the last sensitization, observing the skin and general reactions of each animal 1h, 24h, 48h and 72h after the excitation, grading, and evaluating the skin anaphylactic reaction degree, wherein the negative control group and the positive control group are the same as the test object group. The results of each animal were evaluated for allergic response and allergic intensity.
Tests show that no erythema, edema or other abnormal conditions are observed in the risperidone transdermal patch test group and the blank patch group during the administration process and the observation period. Skin allergic reactions such as erythema, edema and the like are not seen in the test group of the risperidone transdermal patch in the excitation stage and the blank patch group, and systemic allergic reactions such as asthma, unstable standing or shock and the like are not seen in animals of each group. Therefore, the skin allergic reaction is not generated after the skin allergic and excitation of the patch to the guinea pig, which indicates that the patch of the invention is safe and nontoxic to the skin.
Test 3: in vitro transdermal test
For examples 1 to 3 of the present invention and commercially available products
Figure BDA0003129766560000051
(batch ALT224260, expiration date 2021.10; Novartis) for comparison in vitro transdermal tests as follows:
using static diffusion cells
Figure BDA0003129766560000052
The sample was cut to an appropriate area, the protective layer was removed, and the sample was attached to the skin of a female hairless mouse and fixed in a diffusion cell. A magnetic stirrer is arranged in the receiving pool, a receiving medium is HEPES buffer solution with the pH value of 7.20, the water bath temperature of the system is set to be 32 ℃, and the full-automatic transdermal diffusion system is started. Sampling at 0, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h, performing liquid phase analysis, recording the accumulated release amount, and drawing a curve of the accumulated transdermal amount and the time.
In vitro skin penetration test knotFruit display product and commercial product
Figure BDA0003129766560000053
Compared with the traditional Chinese medicine preparation, the medicine transdermal release degree is consistent, and the controlled release effect is better.

Claims (4)

1. A matrix-type transdermal patch containing rivastigmine, wherein the patch comprises: a medicine-containing layer containing active ingredients,
The medicine-containing layer is positioned above the protective layer, and the protective layer is positioned above the back lining layer;
the active ingredient of the drug-containing layer is rivastigmine free base, or a pharmaceutically acceptable salt thereof;
the drug-containing layer is composed of one or more of polyvinyl alcohol, cellulose acetate, acrylate pressure-sensitive adhesive containing carboxyl groups, acrylate pressure-sensitive adhesive containing hydroxyl groups, acrylate pressure-sensitive adhesive containing no functional groups, polybutylene pressure-sensitive adhesive, polysiloxane pressure-sensitive adhesive and natural rubber;
the medicine-containing layer also contains an antioxidant, and the antioxidant consists of one or more of butyl anisole, propyl gallate, tocopherol and dibutyl hydroxy toluene;
the protective layer is one of polyethylene, polystyrene, polypropylene and release paper treated by paraffin or dimethyl silicone oil separant.
2. The matrix transdermal patch according to claim 1, further comprising an adhesive layer and a controlled release membrane; the sticking layer is positioned below the protective layer, and the controlled release film is positioned below the sticking layer;
wherein, the controlled release membrane is one of an ethylene-vinyl acetate copolymer membrane, a polysiloxane membrane, a polypropylene membrane and a cellulose acetate membrane;
the adhesive layer is one or more of polyvinyl alcohol, cellulose acetate, acrylate pressure-sensitive adhesive containing carboxyl groups, acrylate pressure-sensitive adhesive containing hydroxyl groups, acrylate pressure-sensitive adhesive containing no functional groups, polybutylene pressure-sensitive adhesive, polysiloxane pressure-sensitive adhesive and natural rubber.
3. A method of preparing a matrix-type transdermal patch containing rivastigmine according to claim 1, comprising the steps of:
firstly, preparing a medicine-containing layer matrix, and adding an antioxidant into the medicine-containing layer matrix after the matrix is uniformly mixed; dissolving active ingredients with solvent, and adding into drug-loaded matrix containing drug layer; coating the medicine carrying matrix on the protective layer, drying, compounding a backing film, and cutting into a proper size.
4. A method of preparing a matrix-type transdermal patch containing rivastigmine according to claim 2, comprising the steps of: firstly, preparing a medicine-containing layer matrix, and adding an antioxidant into the medicine-containing layer matrix after the matrix is uniformly mixed; dissolving active ingredients with solvent, and adding into drug-loaded matrix containing drug layer; coating the medicine-carrying matrix on the protective layer, and compounding a backing film after drying; preparing an adhesive layer, adding a solvent into the material of the adhesive layer, uniformly mixing, coating the mixture on the other side of the protective layer, drying at 40-80 ℃, compounding the controlled release film on the adhesive layer after drying, removing the protective layer, compounding the drug-containing layer and the adhesive layer, and cutting into a proper area to obtain the controlled release film.
CN202110699680.0A 2021-06-23 2021-06-23 Skeleton type transdermal patch containing rivastigmine and preparation method thereof Pending CN113350318A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1994290A (en) * 2006-01-04 2007-07-11 上海医药工业研究院 Transdermal plaster of rivastigmine and preparation process thereof
CN104523656A (en) * 2014-11-20 2015-04-22 美吉斯制药（厦门）有限公司 Rivastigmine sustained-release transdermal patch and preparation method thereof
CN107929267A (en) * 2017-12-01 2018-04-20 安徽安科余良卿药业有限公司 Transdermal plaster of rivastigmine and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1994290A (en) * 2006-01-04 2007-07-11 上海医药工业研究院 Transdermal plaster of rivastigmine and preparation process thereof
CN104523656A (en) * 2014-11-20 2015-04-22 美吉斯制药（厦门）有限公司 Rivastigmine sustained-release transdermal patch and preparation method thereof
CN107929267A (en) * 2017-12-01 2018-04-20 安徽安科余良卿药业有限公司 Transdermal plaster of rivastigmine and preparation method thereof

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Application publication date: 20210907