CN107951864A - Flurbiprofen cataplasms - Google Patents
Flurbiprofen cataplasms Download PDFInfo
- Publication number
- CN107951864A CN107951864A CN201711261980.0A CN201711261980A CN107951864A CN 107951864 A CN107951864 A CN 107951864A CN 201711261980 A CN201711261980 A CN 201711261980A CN 107951864 A CN107951864 A CN 107951864A
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- China
- Prior art keywords
- flurbiprofen
- phase component
- water
- oil
- drug
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- 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
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
Abstract
Flurbiprofen cataplasms, the cataplasm are made of back sheet, drug-reservoir and protective layer, it is characterized in that the drug-reservoir consists of the following components in percentage by weight：Flurbiprofen 0.2~0.5% as active component；Oil-phase component 5~10%, the oil-phase component is by 1:0.08~0.12 castor oil and phenmethylol composition, the Flurbiprofen are redispersed in castor oil after being first dissolved in phenmethylol；Part as water-phase component neutralizes Sodium Polyacrylate 5 10%, glycerine 15 20%, Dihydroxyaluminium Aminoacetate 0.2%~0.4%, mosatil 0.1%~0.3%, carbomer 934 1%~1.5%, hydroxypropyl methyl cellulose (HPMC) 1.5~3%, pH adjusting agent, gellan gum 0.05~0.1%, L glycine 1%~1.5%；The water of filler 1~3% and surplus, water-phase component form hydrogel with water, and for filler dispersed filler in hydrogel, oil-phase component emulsion dispersion forms drug-reservoir in hydrogel.
Description
Technical field
The present invention relates to flurbiprofen cataplasms.
Background technology
Flurbiprofen (CAS：51543-40-9, flurbiprofen) Flurbiprofen be it is a kind of be used for rheumatoid arthritis,
Osteoarthritis disorders treatment etc. fluorine-containing non-steroidal anti-inflammatory drugs.But traditional Oral administration is in the outer joint, soft of injuring for the treatment of
During the pain that tissue, the inflammation of muscle produce, because needing dosage larger, cause side effect larger, and be unable to control medicine and release
Put, it is difficult to persistently effective easing pain and diminishing inflammation effect is carried out to affected part.Although the pair of oral administration can be reduced using external preparation
Act on and accelerate drug effect speed.But traditional external application mode plays the technique effect of lasting dosed administration.With conventional external application system
Agent is compared, and cataplasm (Cataplasm) has drugloading rate big, promotes drug percutaneous to pass through, and to skin without allergic reaction and thorn
Effect is swashed, the advantages that during stripping without pain and noresidue is drawn.Existing commercially available flurbiprofen cataplasms product, such as Japanese three large bamboo hat with a conical crown and broad brim systems
The flurbiprofen cataplasms of medicine Co., Ltd. production, its specification is 40mg/12g.It is dynamic according to medicine generation disclosed in the package insert
Mechanical Data, for the cataplasm when being applied, onset time is longer, its peak reaching time of blood concentration is 13.8h.Chinese patent
Application CN2017103437803 discloses a kind of flurbiprofen cataplasms, and Flurbiprofen is dissolved in after oil-phase component and is emulsified again
It is scattered in hydrogel and forms drug-reservoir, can not only release the drug continuously and healthily, but also drug release rate can be controlled, so as to significantly improves
The active ingredient Transdermal absorption speed of cataplasm, can realize the quick and continual and steady release of active ingredient, but to its skill
It was found that although the program can improve the drug release situation of Flurbiprofen in the research of art scheme, its Release Performance with
The storage time change of preparation is very fast, causes that clinic can not be applied to, thus provide one kind can quick acting, and realize and continue
Long-time stable releases the drug and Release Performance can keep stable flurbiprofen cataplasms to become existing skill with storage time
Urgent problem to be solved in art.
The content of the invention
For solve aforementioned technical problem, the present invention provides a kind of flurbiprofen cataplasms, the cataplasm by back sheet,
Drug-reservoir and protective layer composition, it is characterized in that the drug-reservoir consists of the following components in percentage by weight：
Flurbiprofen 0.2~0.5% as active component；
Oil-phase component 5~10%, the oil-phase component is by 1:0.08~0.12 castor oil and phenmethylol composition, the fluorine
It is redispersed in after being first dissolved in phenmethylol than ibuprofen in castor oil；
As water-phase component part neutralize Sodium Polyacrylate 5-10%, glycerine 15-20%, Dihydroxyaluminium Aminoacetate 0.2%~
0.4%, mosatil 0.4%~0.6%, carbomer 934 1%~1.5%, hydroxypropyl methyl cellulose (HPMC) 1.5~
3%, pH adjusting agent, gellan gum 0.05~0.1%, L- glycine 1%~1.5%；The water of filler 1~3% and surplus, water
Phase constituent forms hydrogel with water, and in hydrogel, oil-phase component emulsion dispersion is formed filler dispersed filler in hydrogel
Drug-reservoir, the pH adjusting agent are sodium hydroxide and citric acid, and the Citric Acid Dosage is 0.5%~0.7%, the hydrogen-oxygen
Change sodium to adjust the pH of water-phase component to 5.5-6.0.
It is NP700 that the part, which neutralizes acid polyethylene sodium,.The filler is kaolin.
Find under study for action, on the basis of existing flurbiprofen cataplasms, by adjusting mosatil in prescription
Dosage, uses citric acid/sodium hydroxide instead as pH adjusting agent, and replaces sodium carboxymethylcellulose with hydroxypropyl methyl cellulose,
The drug release feature of the preparation that can significantly improve after storing, so as to avoid because under preparation Release Performance caused by storage
Drop, can also keep releasing the drug and controlling continuously and healthily drug release rate after long-term storage, it is saturating to significantly improve active ingredient
Skin infiltration rate, can realize the quick and continual and steady release of active ingredient.And it was found that individually in option screening
Change Calcium Disodium Versenate sodium dosage, using citric acid/sodium hydroxide as pH adjusting agent, to the rear Release Performance after Acceleration study without bright
Aobvious to improve, explanation is that the change of above three formula generates synergistic effect, improves the Release Performance after storage.
Embodiment
Flurbiprofen cataplasms in the embodiment of the present invention are prepared in accordance with the following methods
1) oil-phase component is prepared, and the raw material of oil-phase component is heated to 50-70 DEG C, adds Flurbiprofen micro mist, stirring point
Dissipate and obtain oil phase liquid (1)
2) water-phase component in addition to sodium hydroxide is dissipated in water, is adjusting pH to 5.5-6.0 with sodium hydroxide, obtaining water
Gel, hydrogel is heated to add the oil phase liquid that temperature is 50-70 DEG C after 50~70 DEG C while being stirred with uniform mixer
(1), oil phase stirs evenly after adding filler after adding；Pasta drug-reservoir is obtained after standing vacuum outgas；
3) drug-reservoir is coated on back sheet, and protective layer is attached in upper surface.Obtain flurbiprofen cataplasms.
The specification of the flurbiprofen cataplasms arrived is 3g drug-reservoirs/34cm2Back sheet
In all embodiments and reference examples, it is NP700 (Showa Denko kk productions) that part, which neutralizes Sodium Polyacrylate, hydroxyl
Propyl methocel (HPMC) addition is 2%, and filler is 2% kaolin,.
The citric acid adding amount is with monohydrate potassium (C6H8O7·H2O) count
The formula of embodiment 1~6 see the table below
The formula of the reference examples 1~6 obtained after constituent part in 1~6 prescription of embodiment is adjusted see the table below (with reality
Apply 1~6 identical entry of example not arrange)：
Compared with embodiment 1~6, reference examples 1~, 2 formula does not add citric acid, by Ca-EDTA in reference examples 3-4
The dosage of sodium is adjusted to 0.1%~0.3%, and HPMC is replaced with CMC-Na in reference examples 5-6
Investigated by the cataplasm obtained to embodiment 1~6, it is known that its flat appearance, uniform, drug-reservoir lotion
It is smooth；Mouldability, paste containing amount, initial bonding strength, adhesiveness and film residual quantity meet the requirements.
1 extracorporeal releasing experiment of Pharmacological Examples
According to the 3rd method (paddle dish method, for transdermal in drug release determination method in second annex XD of Chinese Pharmacopoeia 2010 edition
Patch) in the Ba Bu that is obtained to embodiment 1~6 of method that provides be adjacent to anxious drug release determination.Specific method is as follows
Experiment adds dissolution medium in stripping rotor using physiological saline as dissolution medium, pre-temperature to (32 ± 0.5 DEG C) generals bar
Cloth agent removes protective layer, is cut into 2.5cmx7.5cm sizes, keeps flat into bag filter (molecular cut off 14,000), emission surface
Upward, it is placed between two layers of disk, disc edge is clamped bag filter both ends, then be fastened with rubber band, fixes disk.In
10min, 20min, 30min, 45min, 60min, 90min, 2h, 2.5h, 3h and 4h sample 6mL out of stripping rotor respectively, and mend
Isometric (32+0.5) DEG C fresh dissolution medium is filled, parallel test 6, is averaged calculating.Show by detection, the application is real
The vitro release for applying the cataplasm in example reaches more than 90% in 2h.
Pharmacological Examples 2, percutaneous penetration
Using improved Fontan, using in vitro 3 months old rats skin of abdomen as barrier, with embodiment 1~6 and right
1~6 bar cloth patch being prepared carries out carry out permeation test in vitro as usual.Specific experiment method is：
After taking the anesthesia of 3 monthly age healthy rats to put to death, belly wool is eliminated with scissors, removes undamaged skin, is removed subcutaneous
Tissue, is individually fixed in the liberation port of Franz diffusion cells after cleaning, the work release of pH7.4 phosphate buffers is added in receiving chamber and is situated between
Matter, keeps endodermis and solution close contact.The cataplasm for throwing off protective layer is affixed on skin, adjusting water-bath makes outer layer jacket layer
For constant temperature in (32 ± 0.5) DEG C, mixing speed 100rpm, draws release when 0,1h, 2h, 4h, 6h, 8h, 12h are small
Medium 4ml, while add equivalent PBS liquid.Calculating accumulative absorption percentage, (the i.e. accumulative Flurbiprofen passed through is accounted in drug-reservoir
The fractions of Flurbiprofen total amount) result such as following table
The above results show, flurbiprofen cataplasms provided by the invention, when carrying out Transdermal Absorption experiment, 12h
Accumulative medicine transmitance be above 70%, and drug release rate gather way with the time it is more uniform.
Influence of the detection storage of Pharmacological Examples 3 to the release in vitro of medicine
Cataplasm is made in each group of embodiment and comparative example, the lucifuge under the conditions of 40 DEG C is packed and stores 3 months
Percutaneous penetration is carried out according to the method for Pharmacological Examples 2 afterwards, testing result is as follows
Test result indicates that 1~6 each group of embodiment, after 3 months Acceleration studies, its Release Performance maintains substantially
It is constant, but there is obvious decline in the cataplasm of reference examples 1~6 its overall Release Performance, illustrates provided by the invention bar of cloth
Agent prescription can significantly improve cataplasm in the Release Performance after 3 months Acceleration studies by adjusting constituent part.
Claims (2)
1. flurbiprofen cataplasms, the cataplasm is made of back sheet, drug-reservoir and protective layer, it is characterized in that the medicine
Bank consists of the following components in percentage by weight：Flurbiprofen 0.2~0.5% as active component；Oil-phase component 5~
10%, the oil-phase component is by 1:0.08~0.12 castor oil and phenmethylol composition, the Flurbiprofen are first dissolved in phenmethylol
After be redispersed in castor oil；Part as water-phase component neutralizes Sodium Polyacrylate 5-10%, glycerine 15-20%, sweet hydroxyl
Aluminium 0.2%~0.4%, mosatil 0.4%~0.6%, carbomer 934 1%~1.5%, hydroxypropyl methyl cellulose
1.5~3%, pH adjusting agent, gellan gum 0.05~0.1%, L- glycine 1%~1.5%；Filler 1~3% and surplus
Water, water-phase component form hydrogel with water, and filler dispersed filler is in hydrogel, and oil-phase component emulsion dispersion is in hydrogel
Drug-reservoir is formed, the pH adjusting agent is sodium hydroxide and citric acid, and the Citric Acid Dosage is 0.5%~0.7%, described
Sodium hydroxide adjusts the pH of water-phase component to 5.5-6.0.
2. flurbiprofen cataplasms as claimed in claim 1, it is characterized in that it is NP700 that part, which neutralizes acid polyethylene sodium, it is described
Filler is kaolin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711261980.0A CN107951864A (en) | 2017-12-04 | 2017-12-04 | Flurbiprofen cataplasms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711261980.0A CN107951864A (en) | 2017-12-04 | 2017-12-04 | Flurbiprofen cataplasms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107951864A true CN107951864A (en) | 2018-04-24 |
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ID=61963142
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711261980.0A Pending CN107951864A (en) | 2017-12-04 | 2017-12-04 | Flurbiprofen cataplasms |
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| Country | Link |
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| CN (1) | CN107951864A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041236A (en) * | 2021-03-23 | 2021-06-29 | 广州新济药业科技有限公司 | Flurbiprofen cataplasm and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385697A (en) * | 2008-10-30 | 2009-03-18 | 中国科学院上海药物研究所 | Flurbiprofen axetil eye nano-emulsion in-situ gel preparation and preparation method thereof |
| CN102920651A (en) * | 2012-07-23 | 2013-02-13 | 上海工程技术大学 | Flurbiprofen axetil micro-emulsion gel preparation and preparation method thereof |
| CN104546803A (en) * | 2013-10-24 | 2015-04-29 | 和心医药科技（上海）有限公司 | Flurbiprofen hydrogel plaster and composition thereof |
| CN106667970A (en) * | 2016-12-06 | 2017-05-17 | 北京茗泽中和药物研究有限公司 | Flurbiprofen cataplasm |
| CN106822065A (en) * | 2016-12-06 | 2017-06-13 | 北京茗泽中和药物研究有限公司 | A kind of flurbiprofen cataplasms |
| CN107157962A (en) * | 2017-05-16 | 2017-09-15 | 蔡志浩 | flurbiprofen cataplasms |
-
2017
- 2017-12-04 CN CN201711261980.0A patent/CN107951864A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101385697A (en) * | 2008-10-30 | 2009-03-18 | 中国科学院上海药物研究所 | Flurbiprofen axetil eye nano-emulsion in-situ gel preparation and preparation method thereof |
| CN102920651A (en) * | 2012-07-23 | 2013-02-13 | 上海工程技术大学 | Flurbiprofen axetil micro-emulsion gel preparation and preparation method thereof |
| CN104546803A (en) * | 2013-10-24 | 2015-04-29 | 和心医药科技（上海）有限公司 | Flurbiprofen hydrogel plaster and composition thereof |
| CN106667970A (en) * | 2016-12-06 | 2017-05-17 | 北京茗泽中和药物研究有限公司 | Flurbiprofen cataplasm |
| CN106822065A (en) * | 2016-12-06 | 2017-06-13 | 北京茗泽中和药物研究有限公司 | A kind of flurbiprofen cataplasms |
| CN107157962A (en) * | 2017-05-16 | 2017-09-15 | 蔡志浩 | flurbiprofen cataplasms |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041236A (en) * | 2021-03-23 | 2021-06-29 | 广州新济药业科技有限公司 | Flurbiprofen cataplasm and preparation method thereof |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180424 |