CN1813769A - Ciclesonide oral ulcer paster and its preparing method - Google Patents
Ciclesonide oral ulcer paster and its preparing method Download PDFInfo
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- CN1813769A CN1813769A CN 200510057406 CN200510057406A CN1813769A CN 1813769 A CN1813769 A CN 1813769A CN 200510057406 CN200510057406 CN 200510057406 CN 200510057406 A CN200510057406 A CN 200510057406A CN 1813769 A CN1813769 A CN 1813769A
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- ciclesonide
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Abstract
The present invention relates to a sticking tablet for curing stomatocace. Its adhesive layer contains 0.01-2mg of cyclosonide. Said oral sticking tablet can be general single-layer tablet, also can be double-layer tablet including medicine adhesive layer and water-proof protective layer, its adhesive material mainly is selected from hydroxypropyl methyl cellulose, carbopul, carboxymethylcellulose sodium, hydroxypropyl cellulose and polyvinylpyrrolidone.
Description
Technical field
The present invention relates to a kind of Oralease thing, be specifically related to contain the mouth paster and the preparation method of ciclesonide.
Background technology
Oral ulcer is exactly " aphtha " that is commonly called as, and is one of commonly encountered diseases, frequently-occurring disease, and wherein recurrent oral ulceration is the most common, and its sickness rate is more than 20%, and wherein recurrent accounts for 10%.Oral ulcer is to be the oral mucosa limitation infringement of characteristics with intermittence, the special oral mucosa of attacking, usually appear at positions such as maxillary, throat, gingiva, tongue, weight person can be involved pharyngeal and mucosa, the prolongation that has along with the time, and the ulcer area increases, number increases, ulcer surface has violent burn feeling, and pain is made troubles to live and work unbearably.Generation mouth-the eye that has-genitals triad (behcets disease), threat to life.Therefore, to this type of disease, need clinically a kind of easy to use, eutherapeutic pharmaceutical dosage form.
There are sitoesterol film, rifamoin membrane, clotrimazole film etc. in the domestic local application that is used for oral ulcer of having gone on the market at present.These membrane are the monofilm of film material with polyvinyl alcohol or sodium carboxymethyl cellulose generally, and the holdup time in the oral cavity generally is no more than 30 minutes, and is prone to two-way adherent problem, cause medicine can not bring into play long drug effect at the pathological change of oral cavity position.The dexamethasone acetate oral cavity sticking tablet that has gone on the market is double-layer tablet, and medicated layer is that mainly to adopt carbopol be adjuvant to adhered layer.This paster is because the side effect of the easy generation in dexamethasone acetate absorption back glucocorticoids is its shortcoming.
Pharm.Int.1985,6:196 has reported the double-deck oral cavity sticking tablet of the triamcinolone acetonide that Japan produced in 80 years, commodity are called AFTACH.Pastille bed thickness 0.4mm is an alite paste with carbopol and hydroxypropyl emthylcellulose, and the thick 0.7mm of anti-sticking layer (backing) can stick in the oral cavity long period, but easily absorbs, and causes the side effect of general hormones.
The chemical name of ciclesonide: [11 β, 16 α (R)] 16,17-[(cyclohexyl methylene) two (oxygen)]-11-hydroxyl-21-2-methyl isophthalic acid-carboxyl propoxyl group pregnant steroid-1,4-diene-3,20-diketone.Its feature is that antiinflammatory action is strong, and dosage is low, and is long-acting, and only use once every day.Because ciclesonide is extremely sensitive to the oxidase of liver, medicine arrives liver in case absorb the back circulation, eliminates soon, so systemic side effects is little.Ciclesonide is a prodrug, self non-activity, and the lipase by cell is converted into active metabolite, thereby directly brings into play anti-inflammatory activity and analgesic activity at lesions position.
Because these characteristics of ciclesonide, ciclesonide is used for the treatment of the asthma except the aerosol that has gone on the market abroad, it is being developed to the nasal mucosa medicine administration preparation at present abroad, is used for the treatment of rhinitis, and three phases of carrying out are clinical.
Find after deliberation: ciclesonide is made oral cavity sticking tablet, the principal agent ciclesonide is contacted with oral ulcer surface effectively, high molecular bioadhesive prolong drug significantly improves the therapeutic effect of ciclesonide to oral ulcer in the holdup time in affected part.
Summary of the invention
The purpose of this invention is to provide a kind of mouth paster that contains the treatment oral ulcer of ciclesonide, its adhesion layer contains principal agent ciclesonide 0.01-2mg in wherein every single dose paster, and preferred content is 0.05-1mg, more preferably 0.1-0.6mg.
The said ciclesonide mouth paster of the present invention can be single-layer sheet or double-layer tablet, and the single-layer sheet here is common single-layer sheet, only contains the tablet of the adhesion layer of principal agent ciclesonide.
The preferred double-layer tablet of the said mouth paster of the present invention is characterized in that comprising the adhesion layer and the water-fast protective layer that contain the principal agent ciclesonide.
Ciclesonide mouth paster of the present invention, its adhesion material are selected from following one or more materials: hydroxypropyl emthylcellulose, carbopol, sodium carboxymethyl cellulose, hyprolose, polyvinylpyrrolidone, starch, dextrin; In each paster, the gross weight of said adhesion material is 10-60mg.
Ciclesonide mouth paster of the present invention, also comprise pharmaceutically acceptable filler, fluidizer or lubricant, wherein, filler is selected from, a kind of in the middle of the starch, dextrin, mannitol, xylitol, lactose or several, preferred dextrin, lactose, microcrystalline Cellulose; Fluidizer is selected from Pulvis Talci and micropowder silica gel or their compositions, preferably talc powder; Lubricant is selected from Pulvis Talci and magnesium stearate, preferred magnesium stearate.Also further comprise cosolvent in case of necessity, cosolvent is selected from following one or more materials: sodium lauryl sulphate, dodecyl sodium sulfate and tween 80.
Ciclesonide mouth paster of the present invention, said water-fast protective layer are that film former (in case of necessity) is equipped with the fish tail and waterproof layer of the solution spraying of an amount of medicinal plasticizer and filler formation in a surface formation of pastille adhesion layer with acroleic acid resin or ethyl cellulose mainly.Plasticizer is selected from: dibutyl phthalate, diethyl phthalate, dioctyl phthalate, Oleum Ricini; Filler is a titanium dioxide, can add an amount of food coloring as required.
Mouth paster of the present invention is mainly realized by following proposal
A kind of mouth ulcer paster, it by the pastille adhesion layer, protective layer is two-layer forms.
The preparation of adhesion layer tablet: binding agent such as polyvinylpyrrolidone are dissolved in the ethanol, and adding medicine ciclesonide dissolving back is standby; After adhesion material such as hyprolose, carbopol and dextrin mixing, add above-mentioned solution, stir, soft material to be crossed 30 mesh sieves make soft material, after the wet grain oven dry, 30 mesh sieve granulate add the magnesium stearate mixing, tabletting.
With the one side of above-mentioned slice, thin piece of pressing mixed ethanol solution spraying with ethyl cellulose, yellow aluminum color lake, magnesium stearate and dibutyl phthalate; form fish tail and waterproof layer, dry up protective layer then and promptly adhere to and obtain the ciclesonide oral cavity sticking tablet on the medicated layer.
Also can adopt following proposal to realize
A kind of mouth ulcer paster, it by the pastille adhesion layer, protective layer is two-layer forms.Binding agent such as polyvinylpyrrolidone are dissolved in the ethanol, and adding medicine ciclesonide dissolving back is standby; Its medicine adhesion layer is after mixing with adhesion material such as hyprolose, carbopol and dextrin, to add above-mentioned solution, stirs, and soft material is crossed 30 mesh sieves make soft material, and after the wet grain oven dry, 30 sieve granulate add the magnesium stearate mixing and make the adhesion layer granule.
Ethyl cellulose or propanoic acid resin are dissolved in ethanol, make 3% solution for standby.Ethyl cellulose, yellow aluminum color lake and after titanium dioxide mixes add above-mentioned ethyl cellulose or propanoic acid resin solution is made soft material in right amount, soft material is crossed 40 mesh sieves make wet grain, will wet after 60 ℃ of oven dry, add behind the magnesium stearate mixing standby.
Above-mentioned two kinds of material are pressed into double-layer tablet on bi-layer tablet press.
The adhesion material that uses has hydroxypropyl emthylcellulose, carbopol, sodium carboxymethylcellulose pyce, sodium carboxymethyl cellulose, starch, dextrin, polyvinylpyrrolidone, starch, dextrin.In some prescription, can use one or more adhesion materials of different proportion to make good adhesive property through the oral cavity sticking tablet.These adhesion materials delay the effect that the principal agent ciclesonide discharges in addition except having adhesion property, make the medicine long action time.
The protective layer of double layer design is selected ethyl cellulose, acrylic resin for use, and titanium dioxide and magnesium stearate be insoluble macromolecular material under oral conditions, has reduced dissolving and tablet the two-way adhesion oral cavity between of medicine to the oral mucosa offside.In addition, protective layer can adopt spraying method, also can adopt with medicated layer and be pressed into double-layer tablet on the double-layer tablet tablet machine.
Because ciclesonide belongs to steroidal compounds, the water solublity extreme difference, its curative effect of the particle size influences of ciclesonide, in the preparation it is dissolved in the polyvinylpyrrolidone alcoholic solution, by be mixed together the preparation soft material with adjuvant, sieve and make wet grain, wet how strop wherein becomes the very little unformed powder of granularity after drying, improves curative effect.
For the drug release rate of regulating principal agent in the medicated layer and the mouldability of tabletting, sometimes will add excipient in the slice, thin piece prescription, these excipient comprise lactose, xylitol, sorbitol, mannitol, dextrin, starch, micropowder silica gel and magnesium stearate, sodium lauryl sulphate, dodecyl sodium sulfate, tween 80.
The present invention will be further described below in conjunction with embodiment, but not as limitation of the present invention.
Embodiment 1
Medicated layer:
Ciclesonide 0.1g
Hydroxypropyl emthylcellulose 20g
Carbopol 5g
Dextrin 25g
12% polyvinylpyrrolidonesolution solution 9-13ml
Magnesium stearate 0.5g
Make 1000
Method for making: ciclesonide is dissolved in 12% the polyvinylpyrrolidone alcoholic solution.After in addition hydroxypropyl emthylcellulose, carbopol being crossed 80 mesh sieves; mix with dextrin; add the above-mentioned polyvinylpyrrolidonesolution solution system soft material that is dissolved with the medicine ciclesonide; stir; cross and make wet grain behind 35 mesh sieves, the grain that will wet gets dry granular at about 50 ℃ of airpillow-dry, and other goes into tabletting behind the magnesium stearate mixing; the one side of the slice, thin piece of the being pressed ethanol liquid with ethyl cellulose, yellow aluminum color lake and magnesium stearate is coated with, dries up protective layer and promptly adhere to and promptly get the ciclesonide oral cavity sticking tablet on the medicated layer.
Embodiment 2
The present invention will be further described below in conjunction with embodiment, but not as limitation of the present invention.
The medicated layer granule:
Ciclesonide 0.1g
Hydroxypropyl emthylcellulose 20g
Carbopol 5g
Dextrin 25g
12% polyvinylpyrrolidonesolution solution 9-13ml
Magnesium stearate 0.5g
Make 1000
The protective layer granule:
Ethyl cellulose 5g
Titanium dioxide 15g
Yellow aluminum color lake 1.5mg
3% ethyl cellulose alcoholic solution is an amount of
Magnesium stearate 0.01g
Make 1000
Preparation process:
Medicated layer granule method for making: ciclesonide is deeper than in 12% the polyvinylpyrrolidone alcoholic solution.After in addition hydroxypropyl emthylcellulose, carbopol being crossed 80 mesh sieves, mix with dextrin, add the above-mentioned polyvinylpyrrolidonesolution solution system soft material that is dissolved with the medicine ciclesonide, stir, make wet grain after crossing 35 mesh sieves, the grain that will wet gets dry granular at about 50 ℃ of airpillow-dry, and other goes into behind the magnesium stearate mixing standby.
A protective layer material method for making: ethyl cellulose is dissolved in ethanol, makes 3% solution for standby.Ethyl cellulose, yellow aluminum color lake and after titanium dioxide mixes add above-mentioned ethyl cellulose solution and make soft material in right amount, soft material is crossed 40 mesh sieves make wet grain, will wet after 60 ℃ of oven dry, add behind the magnesium stearate mixing standby.
Above-mentioned two kinds of material are pressed into double-layer tablet on bi-layer tablet press.
Embodiment 3
Medicated layer:
Ciclesonide 0.6g
Hydroxypropyl emthylcellulose 20g
Carbopol 5g
Dextrin 25g
12% polyvinylpyrrolidonesolution solution 9-13ml
Magnesium stearate 0.5g
Make 1000
Method for making: just ciclesonide is deeper than in 12% the polyvinylpyrrolidone alcoholic solution.After in addition hydroxypropyl emthylcellulose, carbopol being crossed 80 mesh sieves; mix with dextrin; add the above-mentioned polyvinylpyrrolidonesolution solution system soft material that is dissolved with the medicine ciclesonide; stir; make wet grain after crossing 35 mesh sieves; the grain that will wet gets dry granular at about 50 ℃ of airpillow-dry; other goes into tabletting behind the magnesium stearate mixing; the one side of the slice, thin piece of the being pressed ethanol liquid with ethyl cellulose, magnesium stearate and dibutyl phthalate (6%) is coated with, dries up protective layer and promptly adhere to and promptly get the ciclesonide oral cavity sticking tablet on the medicated layer.
Embodiment 4
The present invention will be further described below in conjunction with embodiment, but not as limitation of the present invention.
Ciclesonide 0.6g
Hydroxypropyl emthylcellulose 20g
Carbopol 5g
Dextrin 25g
12% polyvinylpyrrolidonesolution solution 9-13ml
Magnesium stearate 0.5g
Make 1000
Protective layer:
Ethyl cellulose 5g
Titanium dioxide 15g
3% ethyl cellulose alcoholic solution is an amount of
Yellow aluminum color lake 1.5mg
Magnesium stearate 0.01g
Make 1000
Preparation process
Medicated layer granule method for making: ciclesonide is deeper than in 12% the polyvinylpyrrolidone alcoholic solution.After in addition hydroxypropyl emthylcellulose, carbopol being crossed 80 mesh sieves, mix with dextrin, add the above-mentioned polyvinylpyrrolidonesolution solution system soft material that is dissolved with the medicine ciclesonide, stir, make wet grain after crossing 35 mesh sieves, the grain that will wet gets dry granular at about 50 ℃ of airpillow-dry, and other goes into behind the magnesium stearate mixing standby.
A protective layer material method for making: ethyl cellulose is dissolved in ethanol, makes 3% solution for standby.Ethyl cellulose adds above-mentioned ethyl cellulose solution and makes soft material in right amount with after titanium dioxide is mixed, and soft material is crossed 40 mesh sieves make wet grain, will wet after 60 ℃ of oven dry, adds behind the magnesium stearate mixing standby.
Above-mentioned two kinds of material are pressed into double-layer tablet on bi-layer tablet press.
Product of the present invention is by illumination (2500Lux), high temperature (40 ℃, 60 ℃), 10 days influence factor of placement experiment, quicken the study on the stability that (40 ℃, relative humidity 75%) kept sample 24 months with room temperature in three months, its tablet appearance character, related substance, content etc. have no significant change, and illustrate that the product stability that the present invention makes is good.
The product of the present invention that single dose is contained 0.1mg, 0.6mg ciclesonide is pasted on two groups of oral ulcer rat oral ulcer places, 2 times/day respectively; While also is oral ulcer with other one group but makes comparisons for the rat (matched group) of any processing.Experimental result shows that ulcer area the 2nd, 4,6,8 day of administration two groups of rats of using product of the present invention is all less than matched group (P＜0.05); The average healing rate of group of products of the present invention is faster than matched group (P＜0.05); The congested degree of the edema at the ulcer place of group of products of the present invention is significantly better than matched group; The inflammatory cell quantity at the ulcer place of group of products of the present invention all is less than matched group (P＜0.05) at each time point; The quantity fibroblast of group of products of the present invention is higher than matched group (P＜0.05).And use the intensity of variation of the above index of group of products of the present invention to be dose dependent.Above presentation of results product of the present invention can obviously promote experimental oral ulcer healing containing under the situation of ciclesonide that single dose is 0.1-1mg.
Oral ulcer patient's administration every day 1 time or 2 times.Each a slice is affixed on the affected part.
Claims (11)
1. a Ciclesonide oral ulcer paster is characterized in that its adhesion layer contains principal agent ciclesonide 0.01-1mg in the single dose paster.
2. according to the described ciclesonide mouth paster of claim 1, wherein the content of ciclesonide is preferably 0.1-0.6mg.
3. according to claim 1 or 2 described ciclesonide mouth pasters, it is characterized in that said paster is single-layer sheet or double-layer tablet.
4. according to the described ciclesonide mouth paster of claim 3, wherein said double-layer tablet is characterized in that comprising the adhesion layer and the water-fast protective layer that contain the principal agent ciclesonide.
5. according to claim 1 or 2 described ciclesonide mouth pasters, it is characterized in that adhesion material is selected from following one or more materials: hydroxypropyl emthylcellulose, carbopol, sodium carboxymethyl cellulose, hyprolose, polyvinylpyrrolidone, starch, dextrin.
6. according to the described ciclesonide mouth paster of claim 5, the weight of said adhesion material is 10-60mg.
7. ciclesonide oral cavity sticking tablet according to claim 1 and 2 is characterized in that: also comprise pharmaceutically acceptable filler, fluidizer or lubricant.
8. ciclesonide mouth paster according to claim 7, its filler are selected from a kind of in the middle of the microcrystalline Cellulose, starch, dextrin, mannitol, xylitol, lactose or several; Fluidizer is selected from Pulvis Talci and micropowder silica gel or their compositions; Lubricant is selected from Pulvis Talci and magnesium stearate.
9. according to the described ciclesonide mouth paster of claim 7, it is characterized in that: also further comprise the cosolvent that is selected from following one or more materials: sodium lauryl sulphate, dodecyl sodium sulfate and tween 80.
10. ciclesonide mouth paster according to claim 4; it is characterized in that: said water-fast protective layer is a film former with acroleic acid resin or ethyl cellulose mainly, or is equipped with the fish tail and waterproof layer of the solution spraying of an amount of medicinal plasticizer or filler formation in a surface formation of pastille adhesion layer.
11, a kind of method for preparing the ciclesonide mouth paster is characterized in that: comprise following process:
1) preparation of pastille adhesion layer:
Adhesion material such as polyvinylpyrrolidone are dissolved in the ethanol, standby behind the adding medicine dissolution, after will mixing with adhesion material such as hyprolose, carbopol and dextrin, add above-mentioned solution, stir; Soft material is crossed 30 mesh sieves make soft material, after the wet grain oven dry, 30 mesh sieve granulate add the magnesium stearate mixing and make the adhesion layer granule;
2) preparation of fish tail and waterproof layer:
Ethyl cellulose or acroleic acid resin are dissolved in ethanol, make 3% solution for standby, with adhesion material such as ethyl cellulose, food coloring such as yellow aluminum color lake with after filler such as titanium dioxide mix, add above-mentioned ethyl cellulose or acroleic acid resin solution is made soft material in right amount, soft material is crossed 40 mesh sieves make wet grain, after the grain that will wet is dried, standby behind the adding magnesium stearate mixing;
3) with 1) and 2) two kinds of material making are pressed into double-layer tablet and promptly get mouth paster on bi-layer tablet press.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510057406 CN1813769A (en) | 2005-11-29 | 2005-11-29 | Ciclesonide oral ulcer paster and its preparing method |
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|---|---|---|---|
| CN 200510057406 CN1813769A (en) | 2005-11-29 | 2005-11-29 | Ciclesonide oral ulcer paster and its preparing method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104856979A (en) * | 2015-06-05 | 2015-08-26 | 黄焱 | Carbenoxolone sodium oral patch, and preparation and application thereof |
| CN105193768A (en) * | 2015-08-27 | 2015-12-30 | 武汉武药科技有限公司 | Triamcinolone acetonide oral sticking tablet and preparation process thereof |
| CN107106512A (en) * | 2015-11-25 | 2017-08-29 | 缇碧艾姆株式会社 | Stop blooding and Wound protection film in oral cavity |
| CN107281261A (en) * | 2017-06-25 | 2017-10-24 | 长沙善道新材料科技有限公司 | A kind of mouth ulcer paster easily absorbed and preparation method thereof |
-
2005
- 2005-11-29 CN CN 200510057406 patent/CN1813769A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104856979A (en) * | 2015-06-05 | 2015-08-26 | 黄焱 | Carbenoxolone sodium oral patch, and preparation and application thereof |
| CN105193768A (en) * | 2015-08-27 | 2015-12-30 | 武汉武药科技有限公司 | Triamcinolone acetonide oral sticking tablet and preparation process thereof |
| CN107106512A (en) * | 2015-11-25 | 2017-08-29 | 缇碧艾姆株式会社 | Stop blooding and Wound protection film in oral cavity |
| CN107281261A (en) * | 2017-06-25 | 2017-10-24 | 长沙善道新材料科技有限公司 | A kind of mouth ulcer paster easily absorbed and preparation method thereof |
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