CN101138541B - Amlexanox partial film forming gel composition and uses thereof - Google Patents
Amlexanox partial film forming gel composition and uses thereof Download PDFInfo
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- CN101138541B CN101138541B CN2006100308535A CN200610030853A CN101138541B CN 101138541 B CN101138541 B CN 101138541B CN 2006100308535 A CN2006100308535 A CN 2006100308535A CN 200610030853 A CN200610030853 A CN 200610030853A CN 101138541 B CN101138541 B CN 101138541B
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Abstract
The present invention discloses a compound of an Amlexanox local membrane forming gel, which comprises the components of the following weight percentages comprising 0.5 percentage to 7 percentage alkyl cellulose , 1 percentage to 10 percentage of etherifying agent , 0.5 percentage to 5 percentage of cross linking agent , 75 percentage to 90 percentage of dissolvent , 1 percentage to 10 percentageof Amlexanox. The cross linking agent is the saturated fat or the alcoholic acid, the chemical general formula of which is C<SUB>n</SUB>H<SUB>2n+2-m-l</SUB>(OH)<SUB>m</SUB>(COOH)<SUB>l</SUB>. Among the formula, m or n or 1 is the integer and the n is no less than m, which is no less than 2. 1 is no less than 0 and the result of m plus 1 is 4 to 8. The result of n plus 1 is 4 to 8. In the present invention, the compound of the Amlexanox local membrane forming gel is applied in the treatment of the dental ulcer. A water drain protective membrane with smooth property, firm property, wear-resisting property and duration property is formed on the surface of the ulcer when the present invention is applied. The Amlexanox can be released on the surface of the ulcer after membrane penetration in order to promote the ulcer healing. The membrane can shield the stimulus from the outer world; therefore the pain is greatly reduced.
Description
Technical field
The present invention relates to a kind of amlexanox partial film forming gel composition and the application in the treatment oral ulcer thereof.
Background technology
Stomatocace is the commonly encountered diseases of often meeting in people's daily life.The topical pharmaceutical formulations that is used for the treatment of the disease of cari oris mucosa clinically is generally ointment, ointment, gel, tincture, paste, gargarism etc., often contains various active constituents of medicine, as amlexanox (amlexanox).Amlexanox is as anti-allergic drug at first, has the fat of inhibition hydrido enzyme, suppressing histamine release and leukotriene generates, and the effects such as smooth muscle contraction that cause of antagonism leukotriene, quicken the effect of aphtha healing simultaneously in addition, be one of effective, the most the most frequently used medicine of treatment oral ulcer, now there is the amlexanox paste part of list marketing with the commodity of amlexanox.Because mostly being water-soluble base greatly, the prescription of amlexanox paste forms; when being coated on oral mucosa; can be by the normal activity of therapentic part and surrounding tissue; as friction; the secretion of saliva and flushing make the dissolved and/or corrosion of these medicaments; be shifted, come off, medicament and therapentic part retention time are shorter, make curative effect obviously reduce.
People have studied some can be at skin or moist mucomembranous surface, and the partial film forming gel composition (film-forming gel agent) as oral mucosa surface formation one deck adhesion film can claim again that usually this gellike compositions is the bioadhesive film forming gel composition.The partial film forming gel composition of this class medicine carrying attaches to the body part with the form of film, and a kind of carrier of lasting release medicine can be provided, thereby improves curative effect.About the example of these film-forming compositions open by Rencher (USP5192802,5314915), Tinnell (USP4381296 and 4285934), Promerantz (USP5081158), Epstein (USP5906814), Tapolsky (USP6103266).
Wherein a class partial film forming compositions is normally used water-soluble material, make as Calculus Bovis from Northwest of China Millefolium carboxylic, arabic gum, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, carbomer etc., for example the disclosed adhesion compositions of USP5192802 is made up of sodium carboxymethyl cellulose, xanthan gum, sodium alginate etc.But the adhesion material that this preparation adopted mostly is water-soluble substances greatly, and its holdup time in the affected part is very short, is easy to be eluted from medicine-feeding part by saliva or body fluid.
Another kind of partial film forming gel composition normally forms the hydroxy alkyl cellulose ester with hydroxy alkyl cellulose and esterifying agent reaction, and is crosslinked by cross-linking agent again, is prepared into partial film forming gel.Because the structure of the cross-linking agent that adopts and character is different, this class film forming gel composition forms physical property such as pliability, the adhesion of sticking film, resistance to wear and film widely different holding time of affected part.USP 5081158 disclosed partial film forming gel compositions are composed of the following components: 1) hydroxypropyl cellulose; 2) nontoxic easy volatile solvent is as ethanol; 3) esterifying agent is as salicylic acid and tannic acid (claiming tannin, tannic acid again); 4) cross-linking agent is as boric acid; 5) medicine.Salicylic acid and tannic acid can form the hydroxypropyl cellulose ester with the hydroxyl generation esterification on the hydroxypropyl cellulose as esterifying agent, can produce following effect after hydroxypropyl cellulose ester and boric acid are crosslinked:, this two tunic can be combined after having added cross-linking agent 1. if do not add cross-linking agent and can not form two tunics; 2. can form comparatively tough and tensile, blocky film after crosslinked.According to the report of USP 5906814 and the inventor research to this patent working example, it is thicker and fragile that discovery is made the formed film of cross-linking agent with boric acid, after being applied to the affected part,, have only 4～5 hours as its holdup time on oral mucosa easily by body fluid or saliva corrosion and cause film rupture, come off.USP 5906814 thinks that the reason that causes this phenomenon may be relevant with the structural property of boric acid, three hydroxyls on the boric acid can be crosslinked with three sites on the hydroxypropyl cellulose ester, because three hydroxyl spacings on the boric acid are very near, three crosslinked sites just separated by the space of boron atom, the result causes the product after crosslinked to be strapped in tightly together, formed rigidity, fragile opaque coating.And boric acid has zest to the skin and the mucosa of a lot of individualities.
USP 5906814 discloses another kind of partial film forming gel composition, is with lauric acid monoglyceride substituted boracic acid that with the difference of USP 5081158 as cross-linking agent, other component remains unchanged substantially.Behind hydroxypropyl cellulose and esterifying agent reaction formation hydroxypropyl cellulose ester, can form comparatively flexible film after the usefulness glycerol monolaurate is crosslinked, can improve the fragility of USP5081158 film.But we find the partial film forming gel composition made as cross-linking agent with the lauric acid monoglyceride, though the pliability of its film strengthens to some extent, but the time that is attached on body tissue or the mucosa is then shorter, as the film that on oral mucosa, forms easily by body fluid or saliva corrosion/dissolving, make film break prematurely, come off, so that disappear, its effective holdup time on oral mucosa has only 3～4 hours.
Therefore, as adopt the technology of above-mentioned existing film forming gel composition to prepare the amlexanox partial film forming gel composition, then medicament wherein and affected part retention time shorter, affect the treatment.
Summary of the invention
Purpose of the present invention is intended to solve above-mentioned the problems of the prior art, and a kind of pliability, adhesion, abrasion resistance better and action time of longer amlexanox partial film forming gel composition is provided.
Above-mentioned purpose of the present invention realizes by following technical proposal: amlexanox partial film forming gel composition of the present invention comprises hydroxy alkyl cellulose, esterifying agent, cross-linking agent, solvent, amlexanox; Wherein, this cross-linking agent is saturated fatty polyol or alkyd, and the chemical general formula of this saturated fatty polyol or alkyd is C
nH
2n+2-m-1(OH)
m(COOH)
1, this n, m, 1 are integer, n 〉=m 〉=2,1 〉=0, and m+1 is 4～8, n+1 is 4～8.
Each adjuvant components contents all can be with reference to prior art in the amlexanox partial film forming gel composition of the present invention, and as above-mentioned U.S. Pat P5081158 and the disclosed constituent content of USP5906814, content of medicines system adopts clinical dose therapeutically effective.But amlexanox partial film forming gel composition of the present invention can preferably be selected the content of following percentage by weight for use: hydroxy alkyl cellulose is preferred 0.5%～7%, more preferably 2%～5%; Esterifying agent is preferred 1%～10%, and more preferably 3%～8%; Cross-linking agent is preferred 0.5%～5%, and more preferably 1%～3%; And the treatment effective dose of amlexanox should determine according to concrete feelings to be cured the disease, the patient's that receives treatment age and physiological situation, the degree that is in a bad way, course of treatment factor such as length and medicinal part, and the present invention is preferred 1%～10%, more preferably 3%～7%; And solvent can be 75%～90%, and solvent complements to 100% and gets final product during practical operation, is generally 80%～90%.
Wherein, amlexanox partial film forming gel composition of the present invention can also contain the reinforcing agent below 5%, preferably is 0.5～5%, more preferably is 2%～3%.
In the chemical formula of a preferred embodiment of the present invention, n+1 preferably is no more than 6, and correspondingly m+1 also is no more than 6 usually, promptly can be C
4～C
6Saturated fatty polyol is as daily some used sugar alcohols; Or contain two above hydroxyls, and hydroxyl and carboxyl number are 4～6 C
4～C
6Saturated fat alkyd.
As n=2, m=2,1=2 in the following formula, as tartaric acid, its structural formula is as follows:
Tartaric acid C
4H
6O
6Molecular weight is 150.09
N=m is 5～6 in the molecular formula of another preferred embodiment of the present invention, and as xylitol, mannitol or sorbitol, its structural formula is as follows:
Mannitol C
6H
14O
6Molecular weight is 182.17
Sorbitol C
6H
14O
6Molecular weight is 182.17
Xylitol C
5H
12O
5Molecular weight is 152.15
The molecular weight of saturated fatty polyol of the present invention or alkyd is preferably 122～250, more preferably between 150～183.
Hydroxy alkyl cellulose of the present invention is meant the cellulose that contains 1 above hydroxyl on the side chain at least, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose etc., the preferred hydroxypropyl cellulose of the present invention.
Described esterifying agent is the material that can generate ester with the hydroxyl generation esterification on the hydroxy alkyl cellulose side chain, and as organic carboxylic acid, preferred salicylic acid, tannin or their mixture are the mixture of salicylic acid and tannin best.Salicylic acid and tannin can both be individually and hydroxypropyl cellulose generation esterification, wherein salicylic acid except can with hydroxy alkyl cellulose generation esterification, the hydroxyl on the salicylic acid also can be crosslinked with the form of hydrogen bond with the hydroxyl on the cross-linking agent.
The said reinforcing agent of the present invention is meant hydrophobicity, the wearability that can increase film and/or sticks persistent material.The insoluble alkylcellulose of preferred water of the present invention is as ethyl cellulose, cellulose acetate or their mixture etc.
Described solvent is meant the solvent of various components in the solubilized film forming gel composition and esterification products and cross-linking products.The used solvent of the present invention can be the volatilizable alcoholic solvent that falls, as ethanol, isopropyl alcohol any or its mixture; Or alcoholic solvent and water; It not only can dissolve and carry said components and help gel combination using the position to form film.
Certainly, as required, also can in gel combination, add various additives, as penetration enhancer: laurocapram (Azone), menthol, isopropyl myristate etc.; As antioxidant: vitamin E, vitamin C, sodium sulfite, sodium thiosulfate, butylated hydroxyarisol etc.; Chelating agen: disodium EDTA, EDTA calcium complex disodium salt etc.; Antibacterial: sorbic acid and salt thereof, benzoic acid and salt thereof, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, chlorobutanol etc.; Pigment: solatene, lemon yellow, light blue, sunset yellow, beet red etc.
In a word, except that cross-linking agent by saturated fatty polyol of the present invention or alkyd or its mixture replacing, remaining each component of amlexanox partial film forming gel composition of the present invention: concrete composition or content as hydroxy alkyl cellulose, esterifying agent and solvent etc. all can be with reference to prior aries.
The present invention adopt saturated fatty polyol or alkyd or its mixture in film forming gel composition as cross-linking agent, advantage with following uniqueness: the used cross-linker molecules amount of (1) the present invention is less, preferably as: xylitol, mannitol, sorbitol, tartaric molecular weight are between 150～183, for containing the C that hydroxyl or hydroxyl and carboxyl add up to 4～8
4～C
8Carbon alkane, because that the crosslinkable hydroxyl of cross-linking agent or carboxyl do not have substantially is sterically hindered, its hydrogen bond with the crosslinked back formation of hydroxy alkyl cellulose ester is keeping suitable spacing, makes the film of formation have pliability preferably.(2) the used cross-linking agent of the present invention is the saturated fatty polyol that contains at least 4 hydroxyls, or contain at least 2 hydroxyls, and hydroxyl and carboxyl sum are at least 4 saturated fat alkyd, contain two hydroxyls and two carboxyls as tartaric acid, sorbitol, mannitol and xylitol all contain 5～6 hydroxyls, because these cross-linking agent have more crosslinkable groups can be crosslinked together effectively with a plurality of hydroxy alkyl cellulose ester molecules, it is stronger to form internal bond strength, the network-like complex that quality is bigger, make whole product after crosslinked keep stable, thereby avoided effectively with boric acid or lauric acid monoglyceride as above-mentioned defective that cross-linking agent produced.(3) the present invention selects saturated fatty polyol or the alkyd as cross-linking agent for use, is pharmaceutic adjuvant or food additive as tartaric acid, sorbitol, mannitol and xylitol etc., good biocompatibility, and raw material is easy to get.
The preparation method of film-forming gel agent of the present invention is: add the solvent of an amount of (can dissolve wherein solute) in a container that agitating device is housed, stir down and add amlexanox, esterifying agent successively, make it dissolving; Slowly add hydroxypropyl cellulose, make fully to continue to stir after the dissolving/swelling to make into the even gel shape; Add cross-linking agent (can add reinforcing agent and additive etc. when needing) then successively, continue stirring and make gel even fully, bright; Additional solvent makes and reaches recipe quantity, stirs, and the degassing, promptly.
Amlexanox partial film forming gel composition of the present invention contains the C that hydroxyl or hydroxyl and carboxyl add up to 4～8 owing to having adopted on the chain
4～C
8Carbon alkane is as cross-linking agent, and also the insoluble alkylcellulose of available water is as reinforcing agent, and the film that makes its formation has better tenacity, wearability, persistency and hydrophobicity than other known partial film forming compositions, and its effective holdup time in the affected part is longer.The amlexanox partial film forming gel composition is after the surface, affected part forms film; amlexanox is by discharging to the affected part in the film; make the part, affected part keep the long period, higher concentration; thereby acquisition better therapeutic; in addition; because the barrier protection effect of film can be avoided the stimulation and the infection of outer bound pair wound surface, as drink water, have a meal, extraneous factor stimulation ulcer such as talk or damaged wound and having an intense pain of causing.
Another object of the present invention provides amlexanox partial film forming gel composition of the present invention and is used for the treatment of application in the stomatocace medicine in preparation.
Compositions of the present invention can adopt cotton to wipe away or directly with clean finger gel is coated in the oral mucosa affected part, treat can form in the affected part after the solvent volatilization one deck smooth, tough and tensile, wear-resisting, stick persistent hydrophobic membrane, compare with amlexanox paste of the prior art, amlexanox partial film forming gel composition of the present invention has long action time (about more than 5 hours), film does not have foreign body sensation in the oral cavity, be difficult for being dissolved and/or corrosion, and stick persistent characteristics by saliva of buccal cavity.Amlexanox can see through film and be discharged into the ulcer surface, promotes the ulcer recovery from illness; Formed film can shield the stimulation of outer bound pair ulcer, eases the pain, and improves patient's quality of life greatly.And amlexanox partial film forming gel composition of the present invention is used local non-stimulated to it, safety is good.
The specific embodiment
Following examples are used to describe the present invention, but not as limitation of the present invention.
Various component raw material in the following example are conventional commercially available prod.Wherein the percentage ratio of specified otherwise all is not weight percentage.
Embodiment 1～14 and comparative examples
Respectively with the amlexanox (not adding in the comparative examples) of each consumption and esterifying agent stirring and dissolving in embodiment 1-14 and the comparative examples in the table 1 (with the embodiment of " * " expression) in the solvent of solubilized amount, stir and slowly add hydroxypropyl cellulose down, after making fully dissolving/swelling, continue to stir to make and form the even gel shape; Add cross-linking agent (can add reinforcing agent when needing) then, continue stirring and make fully evenly; Replenish the solvent of surplus, make to reach recipe quantity, stir, the degassing, the partial film forming gel composition that promptly gets amlexanox of the present invention and blank respectively 100 restrains.
Table 1
Experimental result shows that amlexanox partial film forming gel composition outward appearance is bright yellowish-brown, can form on oral mucosa surface one deck smooth, tough and tensile, wear-resisting, stick persistent hydrophobic membrane.
Experimental example 1
Influence factor and study on the stability are carried out in amlexanox partial film forming gel agent to embodiment 1, the result shows this product each influence factor test of 10 days, accelerated test (30 ℃, RH75%) 6 months and room temperature under illumination (4500Lux), high temperature (40 ℃) condition (25 ℃, RH60%) 6 months the study on the stability that keeps sample, its character, uniformity, medicament contg, related substance etc. relatively have no significant change with initial data, the results are shown in Table 2.
Table 2
Experimental example 2
Get the amlexanox partial film forming gel composition that embodiment 2～14 makes, press the sample of the embodiment 1 method preparation of U.S. Pat P5081158, be called for short USP Gel-A, add amlexanox (prescription w/w: amlexanox 5% in the prescription, hydroxypropyl cellulose 2.5%, salicylic acid 2.5%, tannin 7%, boric acid 1%, ethanol 82%), press the sample of the embodiment Gel D method preparation of U.S. Pat P5906814, be called for short USP Gel-B, replace benzocaine (prescription w/w: amlexanox 5% with amlexanox, hydroxypropyl cellulose 1.5%, salicylic acid 2.0%, lauric acid monoglyceride 5.0%, disodium EDTA 0.05%, vitamin E 0.1%, ethanol 86.35% etc.) carrying out external oral mucosa sticks performance, the comparison of corrosion situation and holdup time, the back both in contrast.
Get 3 * 4cm size, fresh beagel dog oral mucosa, prune away the blood vessel and the connective tissue of mucosa inboard, with normal saline soak, washing, dry; The mould circle of internal diameter 16mm, thick 0.6mm is put on the mucosa, respectively above sample is applied in the mould circle, wipe off, after natural drying film forming under the room temperature, take out the mould circle, this mucosa is fixed on the microscope slide with dull and stereotyped.Above microscope slide is fixed on the bottom of digestion instrument container with 45, presses Chinese Pharmacopoeia dissolution method (second method) operation, 900mL distilled water, rotating speed 200rpm.Observe the situation of film on the microscope slide, the results are shown in Table 3.
The external comparison of sticking performance, corrosion situation and holdup time of table 3.
Above result shows that USP Gel-A, USP Gel-B and amlexanox partial film forming gel composition of the present invention all can form one deck and stick film on mucosa, but the film of USP Gel-A, USP Gel-B can be by corrosion, breakage in water.The film that amlexanox partial film forming gel composition of the present invention forms has extremely strong bioadhesive and hydrophobicity, even place more than 10 hours in water, film is kept perfectly substantially and still tightly is attached on the mucosa.
Experimental example 3
Get amlexanox partial film forming gel composition, the sample of above-mentioned USP Gel-A, USP Gel-B and the commercially available Aphthasol Oral Paste (paste that contains 5% amlexanox of embodiment 1,13 preparations, by Japanese Block Drug Company, Inc. produce) carry out the comparison that the rabbit oral mucosa sticks performance, corrosion situation and holdup time, back three is in contrast.
20 rabbit are divided into 5 groups at random, 4 every group.After the rabbit oral cavity pushed aside, dry the moisture of mucomembranous surface in the lower lip of oral cavity, then with mould circle (the about 2cm of area of internal diameter 16mm, thick 0.6mm with clean gauze
2) be flat on mucomembranous surface, respectively above sample is applied in the mould circle, wipe off with dull and stereotyped, preceding 4 gel combinations all form the film that sticks of one deck white after 1 minute, and Aphthasol Oral Paste then forms the linen thin layer of one deck, unclamps the rabbit mouth.Observe the situation of film and measure the diameter of film every 0.5hr,,, the results are shown in Table 4 as performance assessment criteria with membrane area 1/2 timing when above that disappears with compasses.
The comparison of sticking performance, corrosion phenomenon and holdup time in table 4 body
Result of the test shows that 4 gel combinations all can form one deck and stick film on oral mucosa, and Aphthasol Oral Paste then forms the linen thin layer of one deck.The film of USP Gel-B is easily dissolved, existing film destroy, disappearance more than 1/2 after 3 hours; Film destroy, disappearance more than 1/2 were also arranged after 4 hours USP Gel-A months; All disappear behind the Aphthasol Oral Paste 0.5hr; The formed film of amlexanox partial film forming gel composition of embodiment 1 is longer in the holdup time of mucomembranous surface than the formed film of amlexanox film forming gel composition (not containing reinforcing agent) of embodiment 13, be respectively more than 6 hours and about 5 hours, illustrate that adding ethyl cellulose in the prescription of embodiment 1 can prolong the holdup time of film effectively as reinforcing agent; No matter the partial film forming gel of embodiment 1,13 all obviously is better than other 3 control samples in the corrosion situation with on the holdup time.
Experimental example 4
(Inc.) (matched group) is to the contrast test of oral ulcer patient treatment effect for the paste that contains 5% amlexanox, Japanese Block Drug Company for embodiment 1 amlexanox film forming gel composition (test group) and commercially available Aphthasol OralPaste.
1. case is selected: select the patient who suffers from simple property oral ulcer of 16 others health, be divided into two groups at random, 8 every group, the age was at 18～58 years old.
2. ulcer area: measure the ulcer diameter with compasses earlier before the medication, and be converted to area, the results are shown in Table 5.
Table 5
3. usage and dosage: blots the moisture on ulcer surface with clean gauze earlier before the administration, the film forming gel composition of embodiment 1 is extruded about 0.5cm, dip in clean finger and to get, be coated to the ulcer surface then, eupnea just forms the solids adhering film of one deck white after 1 minute; The paste of amlexanox is extruded about 0.5cm, dip in clean finger and get, be coated to the ulcer surface then, administration every day 3 times, each at interval more than 6 hours, continuous use 10 days.
4. detect index and method:
Ulcer healing time and ulcer healing rate: to be covered definite foundation fully by fresh mucosa as the ulcer healing time on the ulcer surface, respectively at after the administration 3,5,7,10 days, measure the ulcer area and observe the ulcer healing situation with compasses, calculate by following formula:
Ulcer healing area %=(original ulcer area one do not heal ulcer area)/original ulcer area * 100%
5. result: ulcer healing time and ulcer healing area percentage the results are shown in Table 6.
Table 6.
Test shows that the amlexanox partial film forming gel has the effect of obvious quickening oral ulcer healing, and therapeutic effect is better than the amlexanox paste.
Experimental example 5
The local excitation of the film forming gel composition (control sample) of observing the amlexanox partial film forming gel composition (test specimen) of embodiment 1 and comparative examples after to rabbit oral mucosa single and multiple dosing reacted.
Method: get 12 of rabbit, be divided into two groups, be respectively single-dose group and multiple dosing group.Be coated with respectively with test specimen and control sample in rabbit oral mucosa both sides, the single-dose group is 1.2mL/ rabbit/sky, and the multiple dosing group is 1.2mL/ rabbit/sky, continuous 7 days, reaches pathological change substantially respectively at 24hr observation after the last administration.
Result of the test shows: overall health of patients, oral cavity and oral mucosa, the respiratory tract of single and multiple dosing group there is no significantly unusual, there was no significant difference between test group and the matched group; Pathological replacement shows that the rabbit oral mucous epithelia is all clear, and as seen subcutaneous on last Intradermal reaches all do not have special pathological changes.Illustrate that amlexanox partial film forming gel composition of the present invention and control sample reach pathology substantially to the oral mucosa of rabbit and all have no stimulation, safety is good.
Claims (9)
1. an amlexanox partial film forming gel composition is characterized in that comprising following components in weight percentage: hydroxy alkyl cellulose 0.5%～7%, esterifying agent 1%～10%, cross-linking agent 0.5%～5%, solvent 75%～90%, amlexanox 1%～10%; Wherein, this esterifying agent is salicylic acid and/or tannin, and this cross-linking agent is saturated fatty polyol or alkyd, and the chemical general formula of this saturated fatty polyol or alkyd is C
nH
2n+2-m-1(OH)
m(COOH)
1, this n, m, 1 are integer, n 〉=m 〉=2,1 〉=0, and m+1 is 4～6, n+1 is 4～6.
2. compositions according to claim 1 is characterized in that this hydroxy alkyl cellulose is 2%～5%, and esterifying agent is 3%～8%, and cross-linking agent is 1%～3%, and solvent is 80%～90%, amlexanox 3%～7%.
3. compositions according to claim 1 and 2 is characterized in that described compositions also comprises 0.5～5% reinforcing agent, and this reinforcing agent is water-insoluble alkylcellulose.
4. compositions according to claim 3 is characterized in that this water-insoluble alkylcellulose is ethyl cellulose and/or cellulose acetate, and its content is 2%～3%.
5. compositions according to claim 1 and 2 is characterized in that this n=m=1=2.
6. compositions according to claim 5 is characterized in that this saturated fatty polyol or alkyd are tartaric acid.
7. compositions according to claim 1 and 2 is characterized in that this n=m is 5～6.
8. compositions according to claim 7 is characterized in that this saturated fatty polyol or alkyd are xylitol, mannitol or sorbitol.
9. amlexanox partial film forming gel composition according to claim 1 and 2 is used for the treatment of application in the medicine of oral ulcer in preparation.
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| CN1582172A (en) * | 2001-11-05 | 2005-02-16 | 奥拉黑尔斯公司 | Treating canker sores with patches to speed healing and relieve pain |
| CN1735393A (en) * | 2002-11-05 | 2006-02-15 | 杰弗瑞·T·黑利 | Soluble oral patch with collagen and interlaced active ingredients |
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