CN106667970B - Flurbiprofen cataplasms - Google Patents
Flurbiprofen cataplasms Download PDFInfo
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- CN106667970B CN106667970B CN201611108639.7A CN201611108639A CN106667970B CN 106667970 B CN106667970 B CN 106667970B CN 201611108639 A CN201611108639 A CN 201611108639A CN 106667970 B CN106667970 B CN 106667970B
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- flurbiprofen
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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
- A61K31/185—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
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- 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
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- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/7061—Polyacrylates
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Flurbiprofen cataplasms are made of back sheet, drug-reservoir and protective layer, and the drug-reservoir consists of the following components in percentage by weight；Flurbiprofen 0.2%~0.5% as active constituent；Oil-phase component 5~10%, the oil-phase component are made of glycerol decanoate, oleic acid and the peregal A-20 that mass ratio is 1:0.2~0.3:0.2~0.3；Flurbiprofen is scattered in oil-phase component；Part as water-phase component neutralizes Sodium Polyacrylate 5-10%, moisturizer 20~40%, Carbopol 0.5%~1.5%, sodium carboxymethylcellulose (CMC-Na) 1.5~3%, Dihydroxyaluminium Aminoacetate 0.2%~0.4%, EDTA-2Na 0.1%~0.3% and Tween-80 0.5~0.7%；The water of filler 1~3% and surplus.
Description
Technical field
The present invention relates to a kind of external preparations of nonsteroidal anti-inflammatory drug, more particularly, to a kind of cataplasm.
Background technique
Flurbiprofen (CAS:51543-40-9, flurbiprofen) molecular formula is as follows:
Flurbiprofen is a kind of fluorine-containing non-steroidal anti-inflammatory drugs, be mainly used for treating rheumatoid arthritis, osteoarthritis,
Ankylosing spondylitis, trauma pain and other pain.Flurbiprofen by inhibit prostaglandin synthetase epoxidase activity from
And play the role of anti-inflammatory analgesic.Compared with oral administration, generated when the inflammation for injuring joint, soft tissue, muscle outside
When pain, the side effect of oral administration can be reduced using external preparation and accelerate drug effect speed.
Cataplasm (Cataplasm), which is meant, to be dissolved drug or is mixed in water-soluble high-molecular material matrix, is coated on
On lining material, a kind of New Percutaneous form of administration used is sticked for skin.Compared with common pharmaceutical preparation, cataplasm is made
For a kind of novel transdermal delivery system, have the advantage that 1) compliance is good；2) liver first-pass effect and stomach and intestine is avoided to inactivate,
To improve therapeutic effect；3) extend drug treating time, reduce times for spraying；4) it controls drug constant speed and enduringly enters people
Body circulation gives full play to drug effect, mitigates adverse drug reaction.Compared with other external patch paste, cataplasm has drugloading rate big,
It is stronger to the bearing capacity of water-soluble component and low ionic strength ingredient；Water content is higher, can strengthen the hydration in skin
Effect promotes drug percutaneous to penetrate, and to skin without allergic reaction and stimulation, without drawing pain and noresidue etc. is excellent when removing
Point.Chinese patent CN031164412 discloses a kind of flurbiprofen cataplasms, and discloses multiple prescriptions, through overtesting we
It was found that specific prescription disclosed in the document does not exist, person's Transdermal absorption speed is slow and the non-uniform defect of drug releasing rate,
It cannot repeat to play the advantage that cataplasm is rapid-action and drug treating time is long.Existing commercially available flurbiprofen cataplasms product,
The flurbiprofen cataplasms of the trade name " obtaining hundred peaces " produced such as Beijing Tide Pharmaceutical Co., Ltd., specification are
40mg/12g.According to pharmacokinetic data disclosed in the package insert, the cataplasm when being applied, onset time compared with
It is long, peak reaching time of blood concentration 13.8h.In conjunction with medication clinic need, provide one kind can quick acting, and realize hold
The flurbiprofen cataplasms of continuous long-time stable drug release become urgent problem to be solved in the prior art.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of flurbiprofen cataplasms, the flurbiprofen cataplasms
It is 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 constituent；
Oil-phase component 5~10%, the oil-phase component are the capric acid glycerol of 1:0.2~0.3:0.2~0.3 by mass ratio
Ester, oleic acid and peregal A-20 composition；Flurbiprofen is scattered in oil-phase component
Part as water-phase component neutralizes Sodium Polyacrylate 5-10%, moisturizer 20~40%, Carbopol 0.5%
~1.5%, sodium carboxymethylcellulose (CMC-Na) 1.5~3%, Dihydroxyaluminium Aminoacetate 0.2%~0.4%, EDTA-2Na 0.1%~
0.3% and Tween-80 0.5~0.7%；The water of filler 1~3% and surplus；Water-phase component and water form hydrogel, filler
For dispersed filler in hydrogel, oil-phase component emulsion dispersion forms drug-reservoir in hydrogel.
It is preferably NP700 that the part, which neutralizes Sodium Polyacrylate,；
The moisturizer is selected from polyethylene glycol, propylene glycol, glycerine, preferably glycerine；
The filler is selected from one or more of kaolin, zinc oxide, calcium carbonate, superfine silica gel powder, titanium dioxide, excellent
It is selected as kaolin.
Flurbiprofen is dissolved in oil and coordinated by flurbiprofen cataplasms provided by the invention on the basis of existing formula
It in point, and is emulsified to be scattered in hydrogel and forms drug-reservoir, under study for action it was found that when preferred oil-phase component
After forming and being separately added into oleic acid and Tween-80 in oil-phase component and water-phase component, improved cataplasm can be significantly improved
Active constituent Transdermal absorption speed, can be realized the quick and continual and steady release of effective component.And under study for action we into
The discovery of one step, the realization of the effect depend on the composition and ratio for depending on oil-phase component, three kinds of ingredients in oil-phase component
Essential and mutual cooperation, the rate of release of effective component can be significantly affected by changing ingredient and proportion, and in water-phase component
Tween-80 then can further improve the release curve of effective component, make it keep higher release fast in the drug release later period
Degree.
Specific 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, and Flurbiprofen micro mist, stirring point is added
It dissipates and obtains oil phase liquid (1)
2) water is dispersed by water-phase component and obtain hydrogel, stir after hydrogel is heated to 50~70 DEG C with uniform mixer
The oil phase liquid (1) that temperature is 50-70 DEG C is added while mixing, oil stirs evenly after adding filler after being added to；Through standing
Drug-reservoir paste is obtained after vacuum outgas；
3) drug-reservoir is coated on back sheet, and attaches protective layer in upper surface.Obtain flurbiprofen cataplasms.?
The specification of the flurbiprofen cataplasms arrived is 3g drug-reservoir/34cm2Back sheet
In all embodiments, it is NP700 (Showa Denko kk production), moisturizer that the part, which neutralizes Sodium Polyacrylate,
For glycerine, filler is 2% kaolin.
By being investigated to the cataplasm that Examples 1 to 6 obtains, 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 paddle dish method, for transdermal of third method in drug release determination method in 2010 editions second annex XD of Chinese Pharmacopoeia
Patch) in total method Ba Bu that embodiment 3,4 is obtained be adjacent to anxious drug release determination.The specific method is as follows
It tests using physiological saline as dissolution medium: dissolution medium is added in stripping rotor, pre-temperature to (32 ± 0.5 DEG C) generals
Cataplasm removes protective layer, is cut into 2.5cmx7.5cm size, lays flat into bag filter (molecular cut off 14,000), discharges
Up, it is placed between two layers of disk, so that disc edge is clamped bag filter both ends, then be fastened with rubber band, to fix disk.
6mL is sampled out of stripping rotor respectively in 10min, 20min, 30min, 45min, 60min, 90min, 2h, 2.5h, 3h and 4h, and
Isometric (32+0.5) DEG C fresh dissolution medium is supplemented, parallel test 6, is averaged calculating, and uses commercially available fluorine ratio simultaneously
Ibuprofen cataplasm (Japanese three large bamboo hat with a conical crown and broad brim Pharmaceutical Co., Ltd production, 40mg/12g, 10cm*13.6cm) is as control.Table after testing
Bright, the vitro release of the cataplasm in control group and the embodiment of the present application reaches 90% or more in 2h.
Pharmacological Examples 2, percutaneous penetration
Using improved Fontan, using in vitro 3 months old rats skin of abdomen as barrier, it is prepared into embodiment 3,4
To cataplasm and commercially available flurbiprofen cataplasms (as positive control) carry out carry out in vitro transdermal test.Specific experiment method
Are as follows:
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 cell after cleaning, the work release of pH7.4 phosphate buffer 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
Temperature is constant at (32 ± 0.5) DEG C, mixing speed 100rpm, is discharged respectively at absorption in 0,1h, 2h, 4h, 6h, 8h, 12h hours
Medium 4ml, while adding equivalent PBS liquid.Calculating accumulative absorption percentage, (the i.e. accumulative Flurbiprofen penetrated accounts in drug-reservoir
The fractions of Flurbiprofen total amount) result such as following table
The above results show flurbiprofen cataplasms provided by the invention, test Shi Yuxian carrying out Transdermal Absorption
The commercially available flurbiprofen cataplasms having are compared, and better percutaneous abilities are shown.Illustrate in the technical solution adopted by the present invention,
The Transdermal absorption performance of flurbiprofen cataplasms is significantly improved by the composition of preferred oil-phase component respectively and water-phase component.?
It was found that using the oil-phase component prescription based on glycerol decanoate in formulation optimization, especially preferred glycerol decanoate,
The proportion of peregal and oleic acid, and in water phase be added recipe quantity Tween-80, for improve Flurbiprofen percutaneous absorbability
Effect outstanding can be generated.And the effect and Flurbiprofen have certain relevance, when change prescription or use other
When active constituent, the Transdermal absorption effect of obtained cataplasm is not as good as flurbiprofen cataplasms provided by the invention.
Claims (1)
1. flurbiprofen cataplasms are made of back sheet, drug-reservoir and protective layer, it is characterized in that the drug-reservoir is by following
The group of weight percent is grouped as:
Flurbiprofen 0.2%~0.5% as active constituent；
Oil-phase component 5~10%, the oil-phase component are glycerol decanoate, the oil of 1:0.2~0.3:0.2~0.3 by mass ratio
Acid and peregal A-20 composition；Flurbiprofen is scattered in oil-phase component；
As water-phase component part neutralize Sodium Polyacrylate 5-10%, moisturizer 20~40%, Carbopol 0.5%~
1.5%, sodium carboxymethylcellulose (CMC-Na) 1.5~3%, Dihydroxyaluminium Aminoacetate 0.2%~0.4%, EDTA-2Na 0.1%~0.3%
With Tween-80 0.5~0.7%；The water of filler 1~3% and surplus；Water-phase component and water form hydrogel, filler dispersion
It is filled in hydrogel, oil-phase component emulsion dispersion forms drug-reservoir in hydrogel；
It is NP700 that the part, which neutralizes Sodium Polyacrylate, and the moisturizer is glycerine, and the filler is kaolin, oxidation
One or more of zinc, calcium carbonate, superfine silica gel powder, titanium dioxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611108639.7A CN106667970B (en) | 2016-12-06 | 2016-12-06 | Flurbiprofen cataplasms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611108639.7A CN106667970B (en) | 2016-12-06 | 2016-12-06 | Flurbiprofen cataplasms |
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| Publication Number | Publication Date |
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| CN106667970A CN106667970A (en) | 2017-05-17 |
| CN106667970B true CN106667970B (en) | 2019-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201611108639.7A Active CN106667970B (en) | 2016-12-06 | 2016-12-06 | Flurbiprofen cataplasms |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110787150A (en) * | 2017-11-21 | 2020-02-14 | 北京泰德制药股份有限公司 | A skin external preparation containing flurbiprofen |
| 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 |
| CN115969776B (en) * | 2023-02-06 | 2023-08-29 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel composition and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN101780169A (en) * | 2010-03-10 | 2010-07-21 | 广州白云山制药股份有限公司白云山何济公制药厂 | Traumatic injury analgesic cataplasm preparation and preparation method thereof |
| CN103040792A (en) * | 2013-01-08 | 2013-04-17 | 常熟雷允上制药有限公司 | Substrate of traditional Chinese medicine cataplasm |
| 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 |
| CN106074453A (en) * | 2016-06-14 | 2016-11-09 | 浙江中医药大学 | Lappaconitine Gel plaster and preparation method thereof |
-
2016
- 2016-12-06 CN CN201611108639.7A patent/CN106667970B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN101780169A (en) * | 2010-03-10 | 2010-07-21 | 广州白云山制药股份有限公司白云山何济公制药厂 | Traumatic injury analgesic cataplasm preparation and preparation method thereof |
| CN103040792A (en) * | 2013-01-08 | 2013-04-17 | 常熟雷允上制药有限公司 | Substrate of traditional Chinese medicine cataplasm |
| 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 |
| CN106074453A (en) * | 2016-06-14 | 2016-11-09 | 浙江中医药大学 | Lappaconitine Gel plaster and preparation method thereof |
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