CN1850059A - Amlexanox oral membrane, and its preparing method - Google Patents
Amlexanox oral membrane, and its preparing method Download PDFInfo
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- CN1850059A CN1850059A CN 200610044323 CN200610044323A CN1850059A CN 1850059 A CN1850059 A CN 1850059A CN 200610044323 CN200610044323 CN 200610044323 CN 200610044323 A CN200610044323 A CN 200610044323A CN 1850059 A CN1850059 A CN 1850059A
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Abstract
The present invention relates to an amlexanox oral membrane preparation and its preparation method. Is composition contains amlexanox, polyvinyl alcohol, glycerine and purified water. Said invention can be used for effectively curing ulcerative stomatitis.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation for the treatment of oral disease, particularly relate to pelliculae pro cavo oris of a kind of medicine amlexanox for the treatment of oral ulcer and preparation method thereof.
Background technology
Oral ulcer is a kind of common disease of cari oris mucosa, claims aphtha again, and pain is very obvious during outbreak, but untreated and spontaneous recovery.The outbreak repeatedly that also has is called recurrent oral ulceration, and patient's work and life caused very big influence.At present, the types of drugs of treatment oral ulcer is various, and existing Western medicine also has Chinese medicine.Western medicine mainly contains medicines such as steroid hormone, all kinds of antibiotic, vitamin, but because factors such as curative effect and side reaction have influenced choosing and using of patient.Chinese medicine mainly contains powders such as BINGPENG SAN, XILEI SAN, but ulcer surface is had strong impulse, uses inconvenience, has limited the extensive use of this medicine.
(aphtha, recurrent aphthous ulcer RAU) are a kind of common disease of cari oris mucosa, the sickness rate in the crowd about 20% to the cyclic recurrence oral ulcer.Morbidity back ulcer surface has violent burn feeling, and pain and influence diet, in a minute unbearably, thereby brings inconvenience to live and work.Data shows that this disease is a frequently-occurring disease, commonly encountered diseases, about 25% population trouble in various degree oral ulcer, wherein have 50% every two, three months or the recurrence of shorter cycle.This sick pathogeny may be local wound or stress, other as systemic disease, malnutrition, food anaphylaxis, infection, immunologic derangement, take other medicines, HIV and infect etc. and all may cause oral ulcer.
The primary and foremost purpose of treatment oral ulcer is to ease the pain, shorten the ulcer persistent period, recovers the oral cavity normal function, secondly is to be devoted to reduce the recurrent number and the order of severity.Local application as antibiotic collutory, topical corticosteroids medicine, can reach first purpose, but does not change recurrence period and recovery rate.
Amlexanox (Amlexanox) chemistry is by name: 2-amino-7-(1-isopropyl)-5-oxygen-5H[1] .alpha.-5:6-benzopyran [2,3-b] pyridine-3-carboxylic acid.It is a kind of antiinflammatory Claritin of Block and the cooperative development of A Saisi pharmacy (Access Pharmaceuticals) company.This medicine can effectively promote the healing of ulcer surface, eases the pain and reduces the ulcer area.Wherein to oral mucosa nonirritant and anaphylaxis, the ill effect of this medicine is rare, is a kind of safe medicine of oral ulcer for the treatment of.This medicine 5% oral cavity paste goes on the market in U.S.'s approval as stomatocace medicine in December, 1996.
The pharmacological action of amlexanox mainly is antiallergic, antiinflammatory, acceleration ulcer healing.In vitro study confirms, amlexanox can suppress mastocyte forcefully, bite inflammatory mediator in neutrophilic leukocyte and the mononuclear cell formation and the release of (histamine, leukotriene), show that amlexanox has resistance attitude and anti-inflammatory activity, can suppress anaphylactic type and delayed hypersensitivity.
Reported that abroad 5% amlexanox paste is used for the clinical research of human body.For example, in a research, 100 four administrations oral ulcer patient every day, continuous 28 days, do not see tangible part or systemic side effects, this experiment confirm the safety of amlexanox paste.Its drug effect is confirmed by the contrast clinical research: in three contrast clinical researches, 464 examples are slightly accepted 5% Amlexanox oral paste treatment to moderate oral ulcer patient: 465 routine patients accept excipient; 195 examples are left intact.The result confirms that 5% Amlexanox oral paste can obviously quicken the healing of oral ulcer.
Because paste uses inconvenience, be difficult to adapt to oral ulcer patient's needs, pelliculae pro cavo oris is a new formulation form in recent years, be suitable for oral ulcer patient use, but amlexanox do not made the report of pelliculae pro cavo oris in the prior art, because the amlexanox taste is extremely bitter, be attached to for a long time in the oral cavity and can cause discomfort, the amlexanox instability need find suitable stabilizers simultaneously, and therefore seeking appropriate ingredients makes the task that pelliculae pro cavo oris is a pharmacy man with amlexanox.
Summary of the invention
Amlexanox is a kind of medicine that can accelerate ulcer healing.Experiment in vitro studies show that amlexanox can effectively suppress mastocyte, neutrophilic granulocyte and mononuclear cell and discharge inflammatory mediator.The result of animal oral application amlexanox shows that amlexanox has antiallergic and anti-inflammatory activity.Continuous 2 years of rat, mice were used amlexanox in the mouth in 18 months, and the result shows no carcinogenesis.Body is interior, external mutagenicity test result is negative.During 200 times of rat dosage behaviour recommended dose, to there not being reproduction, fertility obvious influence.
The invention provides a kind of is the oral film preparation of active constituents of medicine with the amlexanox, and this membrane is made up of the amlexanox of physiology effective dose and an amount of medicine acceptable carrier that can be used in the preparation pelliculae pro cavo oris.
Described medicine acceptable carrier includes but not limited to: polyvinyl alcohol, hypromellose and PEG600 etc.
Because filmogen is varied, much be difficult to reach pharmaceutical standards, the present invention has selected polyvinyl alcohol through research screening repeatedly, and glycerol is filmogen, makes the membrane of the present invention can more long release administration in the ulcer affected part; Both selections simultaneously also make bitterness reduce, and stability is strengthened.
Described polyvinyl alcohol is polyvinyl alcohol (04-86) preferably, in addition, as required, also can add suitable quantity of water when preparation membrane of the present invention.
Membrane of the present invention, its prescription consists of
Amlexanox 1-10g
Polyvinyl alcohol (04-86) 50-100g
Glycerol 5-10ml
Purified water 300-400ml
Make 1000
Membrane of the present invention, preferred prescription consists of
Amlexanox 2.5-10g
Polyvinyl alcohol (04-86) 35-70g
Glycerol 4-16ml
Purified water 165-660ml
Make 1000
Preferred prescription consists of:
Amlexanox 4-6g
Polyvinyl alcohol (04-86) 50-90g
Glycerol 6-10ml
Purified water 260-400ml
Make 1000
Most preferred prescription consists of:
Amlexanox 5g
Polyvinyl alcohol (04-86) 70g
Glycerol 8ml
Purified water 330ml
Make 1000
The present invention preferably fills a prescription, and the preparation method of its preparation is as follows:
1, amlexanox is pulverized the back and crossed 120 mesh sieves, and is standby;
2, amlexanox, the glycerol of recipe quantity is added an amount of purified water and grind to form paste;
3, the polyvinyl alcohol that takes by weighing recipe quantity adds purified water and makes swelling, and heating makes dissolving;
4,2 step gained pastel are added in the 3 step gained solution, fully mixing;
5, suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6, film;
7, the dry laggard interline product of medicine film detect;
8, cut according to content;
9, full inspection, packing, warehouse-in.
Of the present invention filming is: amlexanox is dissolved, is dispersed in the thin film formulations that is processed in the filmogen.
The present invention preferably fills a prescription to form through screening and obtains, and screening process is as follows
Formulation and technology of the present invention is finally determined polyvinyl alcohol through repeated screening research, glycerol, and purified water is respectively as filmogen, plasticizer and solvent.
Prescription is groped (1000 meters)
| Sequence number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 |
| Amlexanox (g) Hydroxypropyl methylcellulose (g) polyvinyl alcohol (05-88) (g) polyvinyl alcohol (17-88) (g) polyvinyl alcohol (04-86) (g) glycerine (ml) PEG600 (g) purified water (ml) investigate index film forming demoulding difficulty or ease | 5 100 ///5/350 is poor | 5 100 // // 5 350 is poor | 5/100 // 5/350 is relatively poor poor | 5/100 ///5 350 is relatively poor | 5 // 100/5/350 is relatively poor | 5 // 100 // 5 350 is relatively poor | 5 ///100 5/350 better | 5 ///100/5 350 is relatively poor | 5 ///70 5/330 more carefully | 5 ///70 6.5/330 more carefully | 5 ///70 8/330 carefully |
| Medicine film flexibility | Difference | Difference | Relatively poor | Relatively poor | Relatively poor | Relatively poor | Better | Better | Good | Good | Good |
The principal agent amlexanox is 5g, and film former is selected polyvinyl alcohol (04-86) 70g, and plasticizer is selected glycerol 8ml, and solvent is selected purified water 330ml, makes 1000.Above prescription ratio is an optimal proportion, and principal agent is 1-10g, and polyvinyl alcohol (04-86) is 50-100g, and glycerol is 5-10ml, and purified water is that 300-400ml also can obtain Amlexanox oral film preferably.
Amlexanox oral film of the present invention prepares by the following method:
1), amlexanox pulverizes the back and cross 120 mesh sieves, and is standby;
2), amlexanox, the glycerol of recipe quantity is added an amount of purified water and grind to form paste;
3), the polyvinyl alcohol that takes by weighing recipe quantity adds purified water makes swelling, and heating makes dissolving;
4), 2 step gained pastel are added in the 3 step gained solution abundant mixing;
5), suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6), film drying.
This product is dissolved the time limit algoscopy with reference to Chinese Pharmacopoeia version in 2000 and has been measured dissolving the time limit of Amlexanox oral film, and the result shows that this product on average melted onset rapidly at 11 minutes.
Pelliculae pro cavo oris of the present invention has been carried out stability experiment, has tested as follows:
1. influence factor's test
Get the pelliculae pro cavo oris sample (lot number: 030321) remove outer package of some, put under illumination (4500Lx), high temperature (60 ℃), high humidity (RH92.5%), the condition and place, in sampling in 5 days, 10 days, according to the method for clinical research with quality standard (draft), the character of working sample, related substance, content, dissolve the time limit, and compare the stability of observation sample with 0 day sample.
Measurement result sees Table 1.Under these conditions after 10 days, the sample moisture absorption is dissolved under high humidity (RH92.5%) condition by the visible sample of table, and other each test item is not seen significant change.
2. accelerated test:
Get three batches of test samples (lot number 030321,030322,030323), the band outer package, under 40 ℃, RH75% condition, place, in 1,2,3, the sampling in June, according to clinical research drug standard (draft) method, the character of working sample, related substance, content, dissolve the time limit, and compare the stability of observation sample with 0 month data.
Result of the test sees Table 2.The result shows this product through above-mentioned condition accelerated test after 6 months, and test item has no significant change, and illustrates that this product is stable under airtight condition.
3. test for a long time keeps sample:
Get three batches of test samples (lot number 030321,030322,030323), the band outer package, under room temperature (25 ℃, RH60%) condition, place, in 3,6,9, the December sampling, according to clinical research drug standard (draft) method, the character of working sample, content, related substance, dissolve the time limit, and compare the stability of observation sample with 0 month data.
Result of the test sees Table 3.The result shows this product after room temperature is placed 12 months, and test item has no significant change.
Table 1 Amlexanox oral film influence factor's result of the test (030321)
| Experimental condition | Time (my god) | Character | Content (%) | Related substance (%) | Dissolve the time limit |
| 0 | The translucent medicine film of off-white color | 99.89 | 0.41 | Up to specification | |
| Illumination 4500 ± 500 Lx | 5 10 | The translucent medicine film of the translucent medicine film of off-white color off-white color | 99.70 99.71 | 0.44 0.51 | Up to specification |
| 60 ℃ of high temperature | 5 10 | The translucent medicine film of the little yellow of the translucent medicine film of off-white color | 99.76 99.71 | 0.46 0.58 | Up to specification |
| High humidity (RH92.5%) | 5 10 | The surfaces of tacky moisture absorption is dissolved | -- -- | -- -- | -- -- |
Table 2 Amlexanox oral film accelerated test stability result
| Lot number | Time (moon) | Character | Content (%) | Related substance (%) | Dissolve the time limit |
| 030321 | 0 | The translucent medicine film of off-white color | 99.89 | 0.41 | Up to specification |
| 1 | The translucent medicine film of off-white color | 99.88 | 0.46 | Up to specification | |
| 2 | The translucent medicine film of off-white color | 99.80 | 0.48 | Up to specification | |
| 3 | The translucent medicine film of off-white color | 99.74 | 0.53 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.61 | 0.60 | Up to specification | |
| 030322 | 0 | The translucent medicine film of off-white color | 99.99 | 0.37 | Up to specification |
| 1 | The translucent medicine film of off-white color | 99.94 | 0.44 | Up to specification | |
| 2 | The translucent medicine film of off-white color | 99.87 | 0.46 | Up to specification | |
| 3 | The translucent medicine film of off-white color | 99.78 | 0.63 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.62 | 0.63 | Up to specification | |
| 030323 | 0 | The translucent medicine film of off-white color | 99.89 | 0.43 | Up to specification |
| 1 | The translucent medicine film of off-white color | 99.90 | 0.44 | Up to specification | |
| 2 | The translucent medicine film of off-white color | 99.85 | 0.47 | Up to specification | |
| 3 | The translucent medicine film of off-white color | 99.70 | 0.49 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.62 | 0.59 | Up to specification |
Table 3 Amlexanox oral film room temperature long term test stability result
| Lot number | Time (moon) | Character | Content (%) | Related substance (%) | Dissolve the time limit |
| 030321 | 0 | The translucent medicine film of off-white color | 99.89 | 0.41 | Up to specification |
| 3 | The translucent medicine film of off-white color | 99.84 | 0.41 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.82 | 0.54 | Up to specification | |
| 9 | The translucent medicine film of off-white color | 99.77 | 0.56 | Up to specification | |
| 12 | The translucent medicine film of off-white color | 99.80 | 0.51 | Up to specification | |
| 030322 | 0 | The translucent medicine film of off-white color | 99.99 | 0.37 | Up to specification |
| 3 | The translucent medicine film of off-white color | 99.87 | 0.49 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.88 | 0.49 | Up to specification | |
| 9 | The translucent medicine film of off-white color | 99.75 | 0.48 | Up to specification | |
| 12 | The translucent medicine film of off-white color | 99.70 | 0.43 | Up to specification | |
| 030323 | 0 | The translucent medicine film of off-white color | 99.89 | 0.43 | Up to specification |
| 3 | The translucent medicine film of off-white color | 99.80 | 0.47 | Up to specification | |
| 6 | The translucent medicine film of off-white color | 99.79 | 0.50 | Up to specification | |
| 9 | The translucent medicine film of off-white color | 99.80 | 0.48 | Up to specification | |
| 12 | The translucent medicine film of off-white color | 99.73 | 0.55 | Up to specification |
The present invention also comprises the method for oral film preparation of the present invention being carried out quality control, because this dosage form complex process, difficult quality is protected in the production process, and the present invention is through research, found a kind of good method of quality control, made quality obtain strict control in being applied to produce.
Method of quality control of the present invention may further comprise the steps:
To the observation of character, differentiate, check assay.
Wherein check and comprise: uniformity of dosage units, the content of related substance dissolves the time limit, weight differential, the mensuration of indexs such as microbial limit.
Method of quality control of the present invention, concrete grammar is as follows:
1) character this product is the translucent medicine film of off-white color or little yellow.
2) differentiate that the retention time of need testing solution main peak should be consistent with the retention time of reference substance solution main peak in the chromatogram that writes down under the assay item.
3) the inspection related substance is got one of this product, puts in the 25ml measuring bottle, adds an amount of ultrasonic dissolving that makes of 0.1mol/L sodium hydroxide solution, adds mobile phase and is diluted to scale, shakes up, and filters, and gets subsequent filtrate as need testing solution; Precision is measured need testing solution 1ml, puts in the 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and solution shines the method test under the assay item in contrast.Precision is measured contrast solution 10 μ l and is injected chromatograph of liquid, regulate detection sensitivity, make main constituent chromatographic peak peak height be about 10% of full scale, precision is measured need testing solution 10 μ l injection chromatograph of liquid again, the record chromatogram is to 2.5 times of main constituent peak retention time, in the chromatogram as show impurity peaks, measure each impurity peak area and, must not be greater than the main peak area (1.0%) of contrast solution.
Uniformity of dosage units is got one of this product, put in the 100ml measuring bottle, add an amount of ultrasonic dissolving that makes of 0.1mol/L sodium hydroxide solution, add methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 10ml measuring bottle, add methanol and be diluted to scale, shake up, according to assay item method mensuration down, should (two appendix XE of Chinese Pharmacopoeia version in 2000) up to specification.
Dissolving the time limit appoints 10 of the films of getting it filled, get a doubling three times (promptly build up original area 1/8) at every turn, the place of scattering of clamping the medicine film with clip connects in the water that clip immerses 37 ℃ together, the medicine film from immerse water to dissolving and the time of dialysis clip should be no more than 15 minutes.
Other should meet every regulation relevant under the membrane item (two appendix IM of Chinese Pharmacopoeia version in 2000).
4) assay is measured according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; With methanol-water-triethylamine (63: 37: 0.2) (regulating pH value to 7.0 with glacial acetic acid) is mobile phase; The detection wavelength is 243nm.Number of theoretical plate calculates by main peak should be not less than 2000, and the separating degree of main peak and other impurity peaks should meet the requirements.
Algoscopy is got 20 of this product, and accurate the title decides, and shreds, and precision takes by weighing in right amount (being equivalent to amlexanox 2.5mg approximately), put in the 100ml measuring bottle, add the 0.1mol/L sodium hydroxide solution and make dissolving in right amount, add methanol to scale, shake up, filter, get subsequent filtrate as need testing solution; Get need testing solution 10 μ l and inject chromatograph of liquid, the record chromatogram.It is an amount of that precision takes by weighing the amlexanox reference substance in addition, adds the 0.1mol/L sodium hydroxide solution and make dissolving, adds the methanol dilution and make the solution that contains 25 μ g among every 1ml approximately, and product solution with the method operation, is pressed external standard method with calculated by peak area promptly in contrast.
Amlexanox oral film of the present invention, onset is rapid, and is safe and effective, is one of good medicine of treatment oral ulcer.
Amlexanox oral membrane of the present invention is compared with existing dosage form and is had the following advantages:
Content is accurate, absorbs better good stability.Volume is little, and light weight is used, carried and convenient transportation.Preparation technology is simple, helps industrial serialization, brakingization, half aseptic or sterile working.And there is not dust from flying when producing.The pelliculae pro cavo oris filmogen is few, can save adjuvant and packaging material.Pelliculae pro cavo oris of the present invention is compared with other dosage forms, and this product energy long duration of action alleviates the pain that ulcer is brought in ulcer spot, has alleviated the side effect of whole body, passes through effort of the present invention simultaneously, and the product bitterness is lowered, and stability strengthens.
The specific embodiment
The present invention will be further described below by specific embodiment.
Embodiment 1:
Amlexanox 5g
Polyvinyl alcohol (04-86) 70g
Glycerol 8ml
Purified water 330ml
Make 1000
Preparation technology:
1, amlexanox is pulverized the back and crossed 120 mesh sieves, and is standby;
2, amlexanox, the glycerol of recipe quantity is added an amount of purified water and grind to form paste;
3, the polyvinyl alcohol that takes by weighing recipe quantity adds purified water and makes swelling, and heating makes dissolving;
4,2 step gained pastel are added in the 3 step gained solution, fully mixing;
5, suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6, film;
7, the dry laggard interline product of medicine film detect;
8, cut according to content;
9, full inspection, packing, warehouse-in.
Embodiment 2:
Amlexanox 3g
Polyvinyl alcohol (04-86) 70g
Glycerol 8ml
Purified water 330ml
Make 1000
Preparation technology:
1, amlexanox is pulverized the back and crossed 120 mesh sieves, and is standby;
2, amlexanox, the glycerol of recipe quantity is added an amount of purified water and grind to form paste;
3, the polyvinyl alcohol that takes by weighing recipe quantity adds purified water and makes swelling, and heating makes dissolving;
4,2 step gained pastel are added in the 3 step gained solution, fully mixing;
5, suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6, film;
7, the dry laggard interline product of medicine film detect;
8, cut according to content;
9, full inspection, packing, warehouse-in.
Embodiment 3:
Amlexanox 2g
Polyvinyl alcohol (04-86) 70g
Glycerol 8ml
Purified water 330ml
Make 1000
Preparation technology:
1, amlexanox is pulverized the back and crossed 120 mesh sieves, and is standby;
2, amlexanox, the glycerol of recipe quantity is added an amount of purified water and grind to form paste;
3, the polyvinyl alcohol that takes by weighing recipe quantity adds purified water and makes swelling, and heating makes dissolving;
4,2 step gained pastel are added in the 3 step gained solution, fully mixing;
5, suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6, film;
7, the dry laggard interline product of medicine film detect;
8, cut according to content;
9, full inspection, packing, warehouse-in.
Embodiment 4:
Amlexanox 2.5g
Polyvinyl alcohol (04-86) 35g
Glycerol 4ml
Purified water 165ml
Make 1000
Preparation technology is with embodiment 1.
Embodiment 5:
Amlexanox 10g
Polyvinyl alcohol (04-86) 70g
Glycerol 16ml
Purified water 660ml
Make 1000
Preparation technology is with embodiment 1.
Embodiment 6:
Amlexanox 6g
Polyvinyl alcohol (04-86) 90g
Glycerol 10ml
Purified water 400ml
Make 1000
Preparation technology is with embodiment 1.
Embodiment 7:
Amlexanox 4g
Polyvinyl alcohol (04-86) 50g
Glycerol 6ml
Purified water 260ml
Make 1000
Preparation technology is with embodiment 1.
Claims (9)
1, a kind of is the pelliculae pro cavo oris of active constituents of medicine with the amlexanox, and this membrane is made up of the amlexanox of physiology effective dose and an amount of medicine acceptable carrier that can be used in the preparation pelliculae pro cavo oris.
2, the pelliculae pro cavo oris of claim 1 is characterized in that, described medicine acceptable carrier is: polyvinyl alcohol, and G ﹠ W,
Each component composed as follows:
Amlexanox 1-10g
Polyvinyl alcohol 50-100g
Glycerol 5-10ml
Water 300-400ml
Make 1000
3, the pelliculae pro cavo oris of claim 2 is characterized in that, each component composed as follows:
Amlexanox 2.5-10g
Polyvinyl alcohol 35-70g
Glycerol 4-16ml
Purified water 165-660ml
Make 1000
4, the pelliculae pro cavo oris of claim 3 is characterized in that, each component composed as follows:
Amlexanox 4-6g
Polyvinyl alcohol 50-90g
Glycerol 6-10ml
Purified water 260-400ml
Make 1000
5, the pelliculae pro cavo oris of claim 4 is characterized in that, each component composed as follows:
Amlexanox 5g
Polyvinyl alcohol 70g
Glycerol 8ml
Purified water 330ml
Make 1000
6, the preparation method of the pelliculae pro cavo oris of claim 1 is characterized in that, step is as follows:
1), amlexanox pulverizes the back and cross 120 mesh sieves, and is standby;
2), amlexanox, glycerol are added an amount of purified water and grind to form paste;
3), get polyvinyl alcohol and add purified water and make swelling, and heating makes dissolving;
4), 2 step gained pastel are added in the 3 step gained solution abundant mixing;
5), suspension sealing is placed in 60 ℃ of environment is incubated froth breaking;
6), film drying.
7, the method for quality control of the pelliculae pro cavo oris of claim 1 is characterized in that, step is as follows: to the observation of character, differentiate, check assay.
8, the method for quality control of claim 7 is characterized in that, inspection wherein comprises that step is as follows: uniformity of dosage units, the content of related substance dissolves the time limit, weight differential, the mensuration of indexs such as microbial limit.
9, the method for quality control of claim 7, step is as follows:
1) character this product is the translucent medicine film of off-white color or little yellow;
2) differentiate that the retention time of need testing solution main peak should be consistent with the retention time of reference substance solution main peak in the chromatogram that writes down under the assay item;
3) the inspection related substance is got one of this product, puts in the 25ml measuring bottle, adds an amount of ultrasonic dissolving that makes of 0.1mol/L sodium hydroxide solution, adds mobile phase and is diluted to scale, shakes up, and filters, and gets subsequent filtrate as need testing solution; Precision is measured need testing solution 1ml, puts in the 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and solution shines the method test under the assay item in contrast; Precision is measured contrast solution 10 μ l and is injected chromatograph of liquid, regulate detection sensitivity, make main constituent chromatographic peak peak height be about 10% of full scale, precision is measured need testing solution 10 μ l injection chromatograph of liquid again, the record chromatogram is to 2.5 times of main constituent peak retention time, in the chromatogram as show impurity peaks, measure each impurity peak area and, must not be greater than the main peak area (1.0%) of contrast solution;
Uniformity of dosage units is got one of this product, put in the 100ml measuring bottle, add an amount of ultrasonic dissolving that makes of 0.1mol/L sodium hydroxide solution, add methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 10ml measuring bottle, add methanol and be diluted to scale, shake up, according to assay item method mensuration down, should (two appendix XE of Chinese Pharmacopoeia version in 2000) up to specification;
Dissolving the time limit appoints 10 of the films of getting it filled, get a doubling three times (promptly build up original area 1/8) at every turn, the place of scattering of clamping the medicine film with clip connects in the water that clip immerses 37 ℃ together, the medicine film from immerse water to dissolving and the time of dialysis clip should be no more than 15 minutes;
Other should meet every regulation relevant under the membrane item (two appendix IM of Chinese Pharmacopoeia version in 2000);
4) assay is measured according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000);
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; With methanol-water-triethylamine (63: 37: 0.2) (regulating pH value to 7.0 with glacial acetic acid) is mobile phase; The detection wavelength is 243nm; Number of theoretical plate calculates by main peak should be not less than 2000, and the separating degree of main peak and other impurity peaks should meet the requirements;
Algoscopy is got 20 of this product, and accurate the title decides, and shreds, and precision takes by weighing in right amount (being equivalent to amlexanox 2.5mg approximately), put in the 100ml measuring bottle, add the 0.1mol/L sodium hydroxide solution and make dissolving in right amount, add methanol to scale, shake up, filter, get subsequent filtrate as need testing solution; Get need testing solution 10 μ l and inject chromatograph of liquid, the record chromatogram; It is an amount of that precision takes by weighing the amlexanox reference substance in addition, adds the 0.1mol/L sodium hydroxide solution and make dissolving, adds the methanol dilution and make the solution that contains 25 μ g among every 1ml approximately, and product solution with the method operation, is pressed external standard method with calculated by peak area promptly in contrast.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610044323A CN1850059B (en) | 2006-05-29 | 2006-05-29 | Amlexanox oral membrane, and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610044323A CN1850059B (en) | 2006-05-29 | 2006-05-29 | Amlexanox oral membrane, and its preparing method |
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| Publication Number | Publication Date |
|---|---|
| CN1850059A true CN1850059A (en) | 2006-10-25 |
| CN1850059B CN1850059B (en) | 2010-05-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200610044323A Expired - Fee Related CN1850059B (en) | 2006-05-29 | 2006-05-29 | Amlexanox oral membrane, and its preparing method |
Country Status (1)
| Country | Link |
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| CN (1) | CN1850059B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101156834B (en) * | 2007-10-30 | 2010-08-11 | 深圳南粤药业有限公司 | Ammonia temperature responsive form gel and its preparation method |
| CN102429893A (en) * | 2011-11-30 | 2012-05-02 | 四川梓橦宫药业有限公司 | Anti-inflammation and anti-allergy canker sore treating medicament and preparation method thereof |
| CN106697364A (en) * | 2017-01-22 | 2017-05-24 | 河南方圆药业有限公司 | Oral cavity film coating machine production line |
| CN115266966A (en) * | 2022-07-07 | 2022-11-01 | 重庆光谱新材料科技有限公司 | Method for detecting content of dissolved matter of polyvinyl alcohol film |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5362737A (en) * | 1991-04-09 | 1994-11-08 | Chemex Pharmaceuticals, Inc. | Methods of treating aphthous ulcers and other mucocutaneous disorders with amlexanox |
| US6585997B2 (en) * | 2001-08-16 | 2003-07-01 | Access Pharmaceuticals, Inc. | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
| EP2338475A3 (en) * | 2001-11-05 | 2012-08-08 | Orahealth Corporation | Treating canker sores with patches to speed healing and relieve pain |
-
2006
- 2006-05-29 CN CN200610044323A patent/CN1850059B/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101156834B (en) * | 2007-10-30 | 2010-08-11 | 深圳南粤药业有限公司 | Ammonia temperature responsive form gel and its preparation method |
| CN102429893A (en) * | 2011-11-30 | 2012-05-02 | 四川梓橦宫药业有限公司 | Anti-inflammation and anti-allergy canker sore treating medicament and preparation method thereof |
| CN102429893B (en) * | 2011-11-30 | 2013-09-25 | 四川梓橦宫药业有限公司 | Anti-inflammation and anti-allergy canker sore treating medicament and preparation method thereof |
| CN106697364A (en) * | 2017-01-22 | 2017-05-24 | 河南方圆药业有限公司 | Oral cavity film coating machine production line |
| CN106697364B (en) * | 2017-01-22 | 2019-02-22 | 河南方圆药业有限公司 | A kind of oral film film machine production line |
| CN115266966A (en) * | 2022-07-07 | 2022-11-01 | 重庆光谱新材料科技有限公司 | Method for detecting content of dissolved matter of polyvinyl alcohol film |
| CN115266966B (en) * | 2022-07-07 | 2024-05-07 | 重庆光谱新材料科技有限公司 | Method for detecting content of dissolved matter of polyvinyl alcohol film |
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| Publication number | Publication date |
|---|---|
| CN1850059B (en) | 2010-05-12 |
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