CN107157962A - flurbiprofen cataplasms - Google Patents
flurbiprofen cataplasms Download PDFInfo
- Publication number
- CN107157962A CN107157962A CN201710343780.3A CN201710343780A CN107157962A CN 107157962 A CN107157962 A CN 107157962A CN 201710343780 A CN201710343780 A CN 201710343780A CN 107157962 A CN107157962 A CN 107157962A
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- CN
- China
- Prior art keywords
- phase component
- flurbiprofen
- oil
- water
- 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
- A61K47/06—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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Abstract
A kind of flurbiprofen cataplasms, the cataplasm is made up of back sheet, drug-reservoir and protective layer, it is characterized in that the drug-reservoir is consisted of the following components in percentage by weight：It is used as the Flurbiprofen 0.2~0.5% of 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 is first dissolved in being redispersed in castor oil after phenmethylol；Sodium Polyacrylate 5 10% is neutralized as the part of water-phase component, glycerine 15 20%, Dihydroxyaluminium Aminoacetate 0.2%~0.4%, mosatil 0.1~0.3, % carbomer 934s 1%~1.5%, sodium carboxymethylcellulose (CMC Na) 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 and water formation hydrogel, filler dispersed filler is in hydrogel, and 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 NSAIDs.But traditional Oral administration treatment it is outer injure joint, it is soft
During the pain that tissue, the inflammation of muscle are produced, because needing dosage larger, cause side effect larger, and uncontrollable medicine is released
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, without drawing pain and the advantages of noresidue during stripping.Existing commercially available flurbiprofen cataplasms product, such as Japanese three large bamboo hat with a conical crown and broad brim system
The flurbiprofen cataplasms of medicine Co., Ltd. production, its specification is 40mg/12g.In medicine generation, is dynamic according to disclosed in the package insert
Mechanical Data, the cataplasm is when being applied, and onset time is longer, and its peak reaching time of blood concentration is 13.8h.With reference to medication
It is clinical need there is provided one kind can quick acting, and realize that the flurbiprofen cataplasms for stablizing drug release for a long time turn into
Urgent problem to be solved in the prior art.
The content of the invention
To solve aforementioned technical problem, the 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 is consisted of the following components in percentage by weight：
It is used as the Flurbiprofen 0.2~0.5% of 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 first dissolved in being redispersed in castor oil after phenmethylol than ibuprofen；
As water-phase component part neutralize Sodium Polyacrylate 5-10%, glycerine 15-20%, Dihydroxyaluminium Aminoacetate 0.2%~
0.4%, mosatil 0.1~0.3, % carbomer 934s 1%~1.5%, sodium carboxymethylcellulose (CMC-Na) 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 and water formation hydrogel, filler dispersed filler is in hydrogel, and oil-phase component emulsion dispersion is formed in hydrogel
Drug-reservoir.It is NP700 that the part, which neutralizes acid polyethylene sodium,.The pH adjusting agent is to adjust water-phase component pH to 5~6.5
Sodium hydroxide solution, the filler be kaolin.
Find under study for action, Flurbiprofen is dissolved in after oil-phase component again into emulsion dispersion forms medicine storage in hydrogel
Storehouse, can both be released the drug continuously and healthily, and drug release rate can be controlled again, so as to significantly improve the active component Transdermal absorption of cataplasm
Speed, can realize the quick of active ingredient and continual and steady release.And under study for action we have further found that, the effect rely on
Benzene in the composition and ratio and water-phase component of oil-phase component in the addition of special ratios gellan gum and glycine, oil-phase component
Methanol and castor oil screen for us in a variety of conventional greases and solvent to be obtained, and changing composition and proportioning can significantly affect
The rate of release of composition is imitated, and the gellan gum of the special ratios in water-phase component can then make the later stage keep higher with glycine
Rate of release.Three match, so as to get flurbiprofen cataplasms can take into account quickly with sustained release performance.In prescription screening
When we have further found that, selection and the ratio-dependent of gellan gum and L- glycine have specificity, either reduce and wherein appoint
A kind of what composition, or change its consumption, the Release Performance for the cataplasm that can significantly impact, and above-mentioned prescription only in activity
Effect substantially, changes cataplasm made from active component when composition is Flurbiprofen, and its Release Performance is carried significantly lower than the present invention
The flurbiprofen cataplasms of confession.
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 into 50-70 DEG C, adds Flurbiprofen micro mist, stirring point
Dissipate and obtain oil phase liquid (1)
2) water-phase component is dissipated and obtains hydrogel in water, hydrogel is heated to after 50~70 DEG C to be stirred with uniform mixer
The oil phase liquid (1) that temperature is 50-70 DEG C is added simultaneously, and oil phase is added after filler after adding and stirred；Through standing vacuum
The drug-reservoir of paste is obtained after degassing；
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), carboxylic that part, which neutralizes Sodium Polyacrylate,
Sodium carboxymethylcellulose pyce (CMC-Na) addition is 2%, and filler is 2% kaolin.
The formula of embodiment 1~6 see the table below
1~6 formula see the table below in reference examples
Compared with embodiment 1~6, in the formula of reference examples 1~6 part by castor oil replace with soybean oil (reference examples 3,
4) phenmethylol partly, is replaced with into propane diols (reference examples 3,5), changes gellan gum and glycine addition (reference examples 6), is only added
Gellan gum and one kind (reference examples 1,2) in glycine, or it is added without gellan gum and glycine addition (reference examples 6)
By being investigated to the cataplasm that embodiment 1~6 is obtained, 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.
The extracorporeal releasing experiment of Pharmacological Examples 1
According to the 3rd method (oar 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, and pre-temperature to (32 ± 0.5 DEG C) is by 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 two 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
Fill isometric (32+0.5) DEG C fresh dissolution medium, parallel test 6, calculating of averaging.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 prepared carries out carry out permeation test in vitro as usual.Specific experiment method is：
Take after the anesthesia execution of 3 monthly age healthy rats, eliminate belly wool with scissors, remove undamaged skin, remove subcutaneous
Tissue, is individually fixed in addition pH7.4 phosphate buffers work release in the liberation port of Franz diffusion cells, receiving chamber and is situated between after cleaning
Matter, keeps endodermis and solution close contact.The cataplasm for throwing off protective layer is affixed on skin, regulation water-bath makes outer layer jacket layer
Temperature is constant at (32 ± 0.5) DEG C, and mixing speed is 100rpm, and release was drawn respectively at 0,1h, 2h, 4h, 6h, 8h, 12h hours
Medium 4ml, while adding equivalent PBS liquid.Calculating accumulative absorption percentage, (Flurbiprofen for adding up to pass through is accounted in drug-reservoir
The fractions of Flurbiprofen total amount) result such as following table
The above results show, the flurbiprofen cataplasms that the present invention is provided, when carrying out Transdermal Absorption experiment, 12h
Accumulative medicine transmitance be above 70%, and drug release rate is used with time more uniform, the explanation present invention that gathers way
Technical scheme in, by the composition of preferred oil-phase component and water-phase component respectively, both improved the saturating of flurbiprofen cataplasms
Skin infiltration rate, can control medicine more uniform release within the entirely application period again, realize the flat of two kinds of characteristics
Weighing apparatus.In prescription screening we have found that the combination of the preferred castor oil of oil-phase component and phenmethylol, the preferred gellan gum of water-phase component with
The combination of L- glycine, is only provided simultaneously with the mentioned component in the range of prescription, could realize that Flurbiprofen Quick uniform discharges
Effect.By being shown with the control experiment of comparative example, carried out using other conventional oil components such as soybean oils, propane diols simple
Replace (comparative example 3-5), either only add matching somebody with somebody for gellan gum and one kind in glycine or change gellan gum and glycine
Than, the Flurbiprofen releasing effect that can influence, and it was also found that the accessory formula and Flurbiprofen in further experiment
Relevant property, when changing active component, even if using same accessory formula, can not also produce the fluorine that the present invention is provided
The Quick uniform drug release effect having than ibuprofen cataplasm.
Claims (2)
1. a kind of flurbiprofen cataplasms, the cataplasm is made up of back sheet, drug-reservoir and protective layer, it is characterized in that described
Drug-reservoir is consisted of the following components in percentage by weight：It is used as the Flurbiprofen 0.2~0.5% of 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 is first dissolved in benzene first
It is redispersed in after alcohol in castor oil；Sodium Polyacrylate 5-10%, glycerine 15-20% are neutralized as the part of water-phase component, it is sweet
Hydroxyl aluminium 0.2%~0.4%, mosatil 0.1~0.3, % carbomer 934s 1%~1.5%, sodium carboxymethylcellulose
(CMC-Na) 1.5~3%, pH adjusting agent, gellan gum 0.05~0.1%, L- glycine 1%~1.5%；Filler 1~3% with
And the water of surplus, water-phase component and water formation hydrogel, filler dispersed filler in hydrogel, oil-phase component emulsion dispersion in
Drug-reservoir is formed in hydrogel.
2. a kind of flurbiprofen cataplasms as claimed in claim 1, it is characterized in that it is NP700 that part, which neutralizes acid polyethylene sodium,.Institute
It is to adjust water-phase component pH to 5~6.5 sodium hydroxide solution to state pH adjusting agent, and the filler is kaolin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710343780.3A CN107157962A (en) | 2017-05-16 | 2017-05-16 | flurbiprofen cataplasms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710343780.3A CN107157962A (en) | 2017-05-16 | 2017-05-16 | flurbiprofen cataplasms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107157962A true CN107157962A (en) | 2017-09-15 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710343780.3A Pending CN107157962A (en) | 2017-05-16 | 2017-05-16 | flurbiprofen cataplasms |
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| Country | Link |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951864A (en) * | 2017-12-04 | 2018-04-24 | 北京茗泽中和药物研究有限公司 | Flurbiprofen cataplasms |
| CN108096228A (en) * | 2018-01-31 | 2018-06-01 | 北京茗泽中和药物研究有限公司 | Loxoprofen sodium cataplasm |
| CN109172546A (en) * | 2018-09-26 | 2019-01-11 | 北京茗泽中和药物研究有限公司 | Lidocaine gel emplastrum |
| CN109200033A (en) * | 2018-09-26 | 2019-01-15 | 北京茗泽中和药物研究有限公司 | A kind of lidocaine gel emplastrum |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010038861A1 (en) * | 1999-12-16 | 2001-11-08 | Tsung-Min Hsu | Transdermal administration of nonsteroidal anti-inflammatory drugs using hydroxide-releasing agents as permeation enhancers |
| CN1443532A (en) * | 2003-04-17 | 2003-09-24 | 中国人民解放军第二军医大学 | Flurbiprofenbab preparation and its preparation method |
| 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 |
| CN105287361A (en) * | 2015-11-13 | 2016-02-03 | 北京泰德制药股份有限公司 | External preparation containing non-steroid anti-inflammatory drug microemulsion and used for skin |
-
2017
- 2017-05-16 CN CN201710343780.3A patent/CN107157962A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010038861A1 (en) * | 1999-12-16 | 2001-11-08 | Tsung-Min Hsu | Transdermal administration of nonsteroidal anti-inflammatory drugs using hydroxide-releasing agents as permeation enhancers |
| CN1443532A (en) * | 2003-04-17 | 2003-09-24 | 中国人民解放军第二军医大学 | Flurbiprofenbab preparation and its preparation method |
| 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 |
| CN105287361A (en) * | 2015-11-13 | 2016-02-03 | 北京泰德制药股份有限公司 | External preparation containing non-steroid anti-inflammatory drug microemulsion and used for skin |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951864A (en) * | 2017-12-04 | 2018-04-24 | 北京茗泽中和药物研究有限公司 | Flurbiprofen cataplasms |
| CN108096228A (en) * | 2018-01-31 | 2018-06-01 | 北京茗泽中和药物研究有限公司 | Loxoprofen sodium cataplasm |
| CN109172546A (en) * | 2018-09-26 | 2019-01-11 | 北京茗泽中和药物研究有限公司 | Lidocaine gel emplastrum |
| CN109200033A (en) * | 2018-09-26 | 2019-01-15 | 北京茗泽中和药物研究有限公司 | A kind of lidocaine gel emplastrum |
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| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20190515 Address after: 102629 Second Floor and Third Floor of Building 12, No. 50 Huatuo Road, Daxing Biomedical Base, Beijing (Liandong U Valley Biomedical Science and Technology Park) Applicant after: BEIJING MINGZE ZHONGHE MEDICAMENT RESEARCH CO., LTD. Address before: 528139 No. 20, Dushugang New Village Team, Lubao Town, Sanshui District, Foshan City, Guangdong Province Applicant before: Cai Zhihao |
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Application publication date: 20170915 |