CN107823190A - A kind of loperamide hydrochloride patch - Google Patents
A kind of loperamide hydrochloride patch Download PDFInfo
- Publication number
- CN107823190A CN107823190A CN201711075240.8A CN201711075240A CN107823190A CN 107823190 A CN107823190 A CN 107823190A CN 201711075240 A CN201711075240 A CN 201711075240A CN 107823190 A CN107823190 A CN 107823190A
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- CN
- China
- Prior art keywords
- loperamide hydrochloride
- drug containing
- patch according
- loperamide
- polyisobutene
- 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.)
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Classifications
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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
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention is a kind of loperamide hydrochloride patch, belongs to preparation technique field.A kind of loperamide hydrochloride patch of the present invention, it is included successively：Back sheet；At least one drug containing adhesive layer, the drug containing adhesive layer include the loperamide hydrochloride and other pharmaceutically acceptable compositions of the matrix containing polyisobutene；With release liner layer；Wherein the amount of loperamide hydrochloride is 0.5 2.5% (w/w) that the drug containing bonds layer weight.The transdermal patch of the present invention shows the advantage of uniqueness to the percutaneous rate of loperamide hydrochloride, has performance that is more lasting, uniformly releasing the drug.
Description
Technical field
The present invention relates to preparation technique field, and in particular to a kind of loperamide hydrochloride patch.
Background technology
Loperamide, chemical name N, N- dimethyl-α, α-diphenyl -4- (rubigan) -4- hydroxyl -1- piperidines butyryl
Amine, molecular formula C29H33ClN2O2.Loperamide is opioid receptor agonist, passes through μ-opiate receptor of exciting intestinal wall and prevention
The release of acetylcholine and prostaglandin, antagonism smooth muscle contraction, enterocinesia and secretion are reduced so as to reach, extends intestinal contents
Holdup time purpose.
In recent years, research finds that loperamide hydrochloride has the (NK of neurokinin 22) and (NK of neurokinin 33) antagonist-like
Act on (Michael J Keiser, Bryan L Roth, Blaine N Armbruster, et al.Relating prote
In pharmacology by ligand chemistry, NATURE BIOTECHNOLOGY, 2007,25：197-206), may be used
For treating the pain as caused by inflammation or skin acute injury etc., and sunburn, skin are itched, and are disliked caused by seasick (car)
The heart and dizziness, improve the symptoms such as neuropathic pain.The loperamide hydrochloride formulation listed at present is oral formulations, is not suitable for
Clinical treatment for these symptoms；Loperamide hydrochloride percutaneous absorption preparation is compared with conventional oral formulation more suitable for these symptoms
Clinical treatment；Moreover, the property of loperamide hydrochloride is also suitable in preparing transdermal formulation, such as the oil of loperamide hydrochloride
Water partition coefficient (LogP) is 2~3, suitable size (Liang Bingwen, percutaneous drug administration preparation, Beijing：China Medical Science Press,
1992,84,252).
The mouthfeel extreme difference of Loperamide, bitter taste is heavier, therefore is covered using necessary method when being prepared into oral formulations
The firmly medicine caused bad sense of taste in the oral cavity, the compliance for increasing patient be prepare one that oral formulations must solve it is important
Problem.But in art of pharmacy, mainly by beta-cyclodextrin inclusion compound, solid dispersion technology, add flavouring, sugar coating
Or the means such as film coating reach the effect of medicine taste masking.But hidden using beta-cyclodextrin inclusion compound and solid dispersion technology
During taste, condition is difficult to control, and final products must be verified through any special measures, such as X- diffraction, differential thermal analysis (DSC), process
It is numerous and diverse.The method for adding flavouring in the composition is also only applicable no larger excitant and the lighter situation of bitter taste, for such as
The especially big or heavier bitter taste medicine of the excitants such as Loperamide, adds flavouring and not can effectively improve such as Orally dissolving system
The poor taste of agent, granule or supensoid agent.
Japan Patent JP5117149 discloses a kind of sugar coated tablet and thin membrane coated tablet comprising Loperamide and its salt, its
In comprising the Loperamide and its parts by weight of salt 0.1~5%, water-soluble saccharides or the parts by weight of starch 50~95%, cellulose 0~
30% parts by weight, a kind of native metal salt of water-insoluble or its parts by weight of acid 0.2~5%.Its mainly by sugar coating and
The mode of film coating carrys out taste masking, but for some special formulations, such as oral disnitegration tablet, buccal tablet, granule or supensoid agent
Deng the preparation directly contacted in oral cavity with gustatory receptor, it is impossible to carry out flavoring processing using the method for coating.
Publication No. CN1638748A patent discloses the film shape or wafer shape medicine system of a kind of Loperamide taste masking
Agent, it adds the material of at least one formation carbon dioxide in prescription, such as sodium acid carbonate, utilizes the aerogenesis of sodium acid carbonate
The stimulation to taste bud is acted on, so as to reduce the bitter taste of Loperamide.But the preparation prepared using the method is right in storage process
The requirement of environment and packaging material is higher, as air humidity it is larger when, the moisture in air can rise with the sodium acid carbonate in preparation
Reaction generation carbon dioxide, causes the stability of product to decline.
Develop and a kind of both bear the bitter taste of Loperamide active material without patient and drug safety can be improved simultaneously
Product can be that patient brings very big welfare.The especially old man of children or dysphagia, safety issue and drug compliance
Problem is even more important.
The content of the invention
The present invention provides a kind of Loperamide patch safe, bioavilability is high.
The technical scheme for realizing the object of the invention is：
A kind of loperamide hydrochloride patch, it is included successively：
Back sheet；
At least one drug containing adhesive layer, the loperamide hydrochloride of the drug containing adhesive layer including the matrix containing polyisobutene and
Other pharmaceutically acceptable compositions；
With release liner layer；
Wherein the amount of loperamide hydrochloride is the 0.5-2.5% (w/w) that the drug containing bonds layer weight.
The loperamide hydrochloride patch also includes the penetration enhancer less than 4%.
The penetration enhancer is caprolactam N- alkyl compounds, preferably azone, and the dosage of azone is small
In 0.4% (w/w) of drug containing bonding layer weight.
The polyisobutene matrix includes the mixture of polyisobutene or polyisobutene and other polymer, and its amount is preferably
The about 15-99% of the drug containing layer weight, wherein the polymer, which is selected to be formed to have, is no more than above-mentioned drug containing adhesive layer weight
The hydrocarbon polymer and its mixture of the drug containing nitride layer of 3% loperamide hydrochloride solubility of amount.
The drug containing adhesive layer can include hydrocarbon polymer as extra polymer, the hydrocarbon polymer be selected from polybutene,
Polyisoprene, polystyrene, styrene-isoprene-phenylethene block polymer, s-B-S block
Polymer and/or their mixture.The amount of the polyisobutene is the about 15-99% that the drug containing bonds layer weight.
The drug containing nitride layer has viscosity.Preferably, the polymer of the drug containing nitride layer have suitable adhesive property with
So that without other adhesives (sticky agent) such as tackifier (tackifier).No matter when think to need to improve drug containing
The bonding strength of nitride layer, then the layer further include tackifier.
The drug containing nitride layer includes rosin ester as tackifier.
The tackifier account for the 15-30% of drug containing adhesive layer gross weight.
Beneficial effects of the present invention：
Loperamide hydrochloride patch of the present invention shows the advantage of uniqueness to the percutaneous rate of Loperamide, has and more accommodates
Long, the performance uniformly to release the drug.
The present invention due to being that Transdermal absorption security is higher compared with other formulations, and be experimentally confirmed the present invention it is transdermal
Speed and more efficient, thus bioavilability is higher.
Brief description of the drawings
Fig. 1 is loperamide hydrochloride burst size result figure in patch.
Embodiment
Embodiment
Table 1
All embodiments, reference examples and comparative example include the loperamide hydrochloride of identical amount, with guarantee test can
Compare property.
Above-described embodiment, comparative example are prepared according to conventional patch preparation method.
Reference examples are prepared using CN101224206 prescription and method.
Experimental example：Loperamide hydrochloride burst size determines in patch
Above-mentioned patch according to《Percutaneous drug administration preparation》(Liang Bingwen, China Medical Science Press, in September, 1992 publishes 252
Page) introduce experimental method carry out percutaneous penetration.
Experimental facilities：FRANZ transdermal diffusion apparatus (model TK-60B, the triumphant scientific and technological trade Co., Ltd of the Shanghai iron of fine quality)
Experimental vehicle：Using the freshly prepared full thick skin of cavy ribbed back (preparation method reference《Percutaneous drug administration preparation》Beam
Text is grasped, China Medical Science Press, in September, 1992 is published, page 252)
Sample size：5 (each embodiments or the test article of comparative example patch is parallel select 5 samples)
Patch surface accumulates：10cm2
Dispersive medium：PH6.2 phosphate buffers
Assay method：High performance liquid chromatography (UV-detector, Waters companies, model 2487)
Measure embodiment 1, reference examples, comparative example 2-5 patch 1-72 hour loperamide hydrochlorides cumulative release amount (μ
g/cm2), as a result as shown in Figure 1.Cumulative release amount (the μ of the 0-12 hour rotigotines of embodiment 1-3 and comparative example 2-5 patches
g/cm2) as shown in table 1.
By Fig. 1 it can be seen that, meet the embodiment 1 of application claims have compared with the patch of reference examples and other comparative examples compared with
High transdermal release amount, and the characteristics of embody Zero order release；Importantly, it can be seen from Fig. 1 compared with reference examples
Compared with patch of the invention had the drug permeation amount significantly increased at initial 12 hours of dissipation period, that is, meaned to work more
It hurry up.It can be seen from Fig. 1 and table 1 compared with comparative example 2-5 patch, transdermal patch of the present invention is to loperamide hydrochloride
Percutaneous rate shows the advantage of uniqueness, has performance that is more lasting, uniformly releasing the drug.
Claims (10)
1. a kind of loperamide hydrochloride patch, it is included successively：
Back sheet；
At least one drug containing adhesive layer, the loperamide hydrochloride of the drug containing adhesive layer including the matrix containing polyisobutene and other
Pharmaceutically acceptable composition；
With release liner layer；
Wherein the amount of loperamide hydrochloride is the 0.5-2.5% (w/w) that the drug containing bonds layer weight.
A kind of 2. loperamide hydrochloride patch according to claim 1, it is characterised in that：The drug containing adhesive layer also includes
Penetration enhancer less than 4%.
A kind of 3. loperamide hydrochloride patch according to claim 2, it is characterised in that：The penetration enhancer is in oneself
Acid amides N- alkyl compounds.
A kind of 4. loperamide hydrochloride patch according to claim 3, it is characterised in that：The caprolactam N- hydrocarbylations
Compound is azone.
A kind of 5. loperamide hydrochloride patch according to claim 4, it is characterised in that：The amount of the azone is small
In drug containing bonding layer weight 0.5%w/w.
A kind of 6. loperamide hydrochloride patch according to claim 1 or 5, it is characterised in that：The polyisobutene matrix
Mixture comprising polyisobutene or polyisobutene and other polymer.
A kind of 7. loperamide hydrochloride patch according to claim 6, it is characterised in that：The amount of the polyisobutene is institute
State the about 15-99% of drug containing bonding layer weight.
A kind of 8. loperamide hydrochloride patch according to claim 7, it is characterised in that：The drug containing adhesive layer also includes
Tackifier.
A kind of 9. loperamide hydrochloride patch according to claim 8, it is characterised in that：The tackifier are rosin ester.
A kind of 10. loperamide hydrochloride patch according to claim 9, it is characterised in that：The tackifier account for drug containing and glued
Close the 15-30% of layer gross weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711075240.8A CN107823190A (en) | 2017-11-06 | 2017-11-06 | A kind of loperamide hydrochloride patch |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711075240.8A CN107823190A (en) | 2017-11-06 | 2017-11-06 | A kind of loperamide hydrochloride patch |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107823190A true CN107823190A (en) | 2018-03-23 |
Family
ID=61653734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711075240.8A Pending CN107823190A (en) | 2017-11-06 | 2017-11-06 | A kind of loperamide hydrochloride patch |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107823190A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101147739A (en) * | 2007-07-06 | 2008-03-26 | 北京康倍得医药技术开发有限公司 | Composition containing rotigotine and its use and transdermal patch containing the composition |
-
2017
- 2017-11-06 CN CN201711075240.8A patent/CN107823190A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101147739A (en) * | 2007-07-06 | 2008-03-26 | 北京康倍得医药技术开发有限公司 | Composition containing rotigotine and its use and transdermal patch containing the composition |
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Application publication date: 20180323 |
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