CN1939292B - Oral medicinal preparation and oral slow-releasing preparation - Google Patents
Oral medicinal preparation and oral slow-releasing preparation Download PDFInfo
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- CN1939292B CN1939292B CN2005101052536A CN200510105253A CN1939292B CN 1939292 B CN1939292 B CN 1939292B CN 2005101052536 A CN2005101052536 A CN 2005101052536A CN 200510105253 A CN200510105253 A CN 200510105253A CN 1939292 B CN1939292 B CN 1939292B
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- ketoprofen
- acetaminophen
- preparation
- slow
- cellulose
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Abstract
An orally taken slow-release medicine contains ketoprofen and paracetamol, and features high synergistic action and high effect to lower the by-effect of ketoprofen. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of oral drug preparation and oral slow-releasing preparation and preparation method thereof.Described preparation contains ketoprofen and acetaminophen.
Background technology
In order to strengthen medicine to the curative effect of treatment disease, the compliance that improves patient's medication and/or minimizing untoward reaction, adopt the similar medicine of the different mechanisms of action to form compound recipe, this has been a direction of developing drugs.
Ketoprofen belongs to the derivant of benzenpropanoic acid, can suppress the synthetic of peripheral tissues's prostaglandin, has stronger antiinflammatory, analgesia and antipyretic effect.Its antiinflammatory action is bigger 150 times than aspirin, and refrigeration function is stronger 4 times than indometacin, and toxicity only is 1/20 of indometacin, acts on identically with ibuprofen, and antiinflammatory action is strong than ibuprofen, and the untoward reaction of KP is similar to ibuprofen and lighter, generally is easy to tolerance.Acetaminophen belongs to the metabolite of phenacetin, can suppress the synthetic of central position prostaglandin, brings into play analgesic, analgesic activity rapidly, but its antiinflammatory action a little less than.
Summary of the invention:
The object of the present invention is to provide better anti-inflammation analgesis medicament.The inventor finds acetaminophen and ketoprofen gang are used under study for action, and the anti-inflammatory and analgesic effect in the time of can significantly strengthening independent acetaminophen or independent ketoprofen use demonstrates good synergism.Further discover, acetaminophen, ketoprofen and pharmaceutical carrier are mixed can be made into oral slow-releasing preparation.
Therefore, the present invention relates to a kind of oral formulations, it comprises acetaminophen and ketoprofen.
The invention still further relates to a kind of oral slow-releasing preparation, it comprises acetaminophen, ketoprofen, binding agent (lactose, microcrystalline Cellulose), slow-release material, lubricant, fluidizer and damp-proof membrane.
The invention still further relates to acetaminophen and ketoprofen unites and is used for preparation and is used for antiinflammatory, analgesic medicine purposes.
The invention further relates to a kind of preparation method of oral slow-releasing preparation, it comprises acetaminophen, ketoprofen, and binding agent, slow-release material, lubricant, fluidizer mixes with damp-proof membrane.
According to the present invention, coupling ratio to ketoprofen and acetyl aminophenol is: 1: 3.75-1: 15, be preferably 4: 15, or both when share the ratio range of dosage be: acetaminophen 187～1200mg, ketoprofen 50～200mg, preferred dose is acetaminophen 375mg, ketoprofen 100mg, and take once every day.
According to the present invention, oral slow-releasing preparation of the present invention comprises label and the damp-proof membrane that contains acetaminophen, ketoprofen.
Described label is formed (weight %):
Acetaminophen 30%-80%
Ketoprofen 0.5%-4%
Sustained-release matrix material 10%-50%
Binding agent 1%-8%
Lubricant 0.5%-3%
Fluidizer 1%-5%
It is Opadry model opadry II that described damp-proof membrane is formed, slightly soluble type coating materials, coating weightening finish 2%-6% in accordance with regulations
Described sustained-release matrix material say for example be selected from least a: carboxylic propyl methocel K4M, K15M, K100M, the carboxylic third methylcellulose E4M, hydroxypropyl methylcellulose F4M, carbomer 934 p, 974p, 971p, ethyl cellulose, sodium alginate, chitosan or magnesium stearate.Described binding agent say for example be selected from least a: lactose, microcrystalline Cellulose, 30 POVIDONE K 30 BP/USP 30, ethyl cellulose or carboxymethyl cellulose.Described lubricant say for example be selected from least a: magnesium stearate, calcium stearate, Macrogol 4000 or polyethylene glycol 6000.Described fluidizer is: Pulvis Talci or silica gel.
According to the present invention, oral formulations of the present invention or oral slow-releasing preparation can be any form of oral formulations, say for example to can be tablet or capsule.
More specifically say, when oral slow-releasing preparation of the present invention is tablet, can reduce medicining times, every day twice, each a slice.Its drug release feature is not subjected to the gastrointestinal factor affecting, measures constant release in 1-12 hour, Higuchi equation through the release in vitro degree, blood drug level is steady, thereby reduced the toxic and side effects after taking medicine effectively, improved patient's compliance, be fit to the needs of clinical application development.
Specific embodiments
Describe the present invention in detail with embodiment below:
The experiment of embodiment 1 mice acetic acid twisting
Materials and methods: 18～22 gram mices, male and female half and half, 10 every group.The compound recipe that acetaminophen, ketoprofen and acetaminophen and ketoprofen are formed, CMC-Na wiring solution-forming with 0.5%, with the continuous gastric infusion of doses (ig) 3 days, matched group is given 0.5% CMC-Na solution with volume, behind the ig administration 45min, mice is by 0.1 milliliter/10 grams, lumbar injection 0.7% (volume/volume) acetic acid.Behind the injection acetic acid in 15 minutes, calculate the total mice that typical case's " turning round body " reaction (abdominal part indent, stretch hind leg, buttocks is raised) takes place, between organizing with the t check relatively.
Experimental result: the result is as shown in table 1, more than two kinds of medicines all reduce the mouse writhing number of times, compare significant difference with matched group, single medicinal material group.
Embodiment 2 antagonism carrageenin cause the swollen effect of mice foot
The inhibition activity of the edema experiment that the mensuration on Carrageenan is brought out in mice.The mice body weight is 28～32 grams.Continuously gastric infusion (ig) is 3 days, and matched group is given with volume 0.5% CMC-Na solution, behind the last administration 45min, with 0.75% carrageenin 0.05ml/ only at the right sufficient sole of the foot of each Mus portion subcutaneous injection.The tailing edge ankle joint was cut left and right sides foot in 4 hours, weighed respectively, was paw swelling with left and right sides weight difference, and asked suppression ratio.
Experimental result: various dose all can alleviate the foot swelling due to the carrageenin, and is remarkable with matched group and single medicine comparing difference, shows that compound recipe has inflammatory effect due to the antagonism carrageenin, and strong drug action strengthens than single medicinal material.
Embodiment 3 slow releasing tablets of the present invention
Being prepared as follows of slow releasing tablet of the present invention:
Respectively acetaminophen, ketoprofen, lactose, microcrystalline Cellulose, magnesium stearate, Pulvis Talci, hydroxypropyl emthylcellulose are pressed above-mentioned component and content drying, pulverize, cross 100 mesh sieves respectively, standby.
Respectively with acetaminophen, ketoprofen, lactose, sustained-release matrix material, cross 80 mesh sieve mix homogeneously then.The ethanol of adding 95% is made soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure, crosses 20 mesh sieves and granulates; Drying is 6 hours under 40 ℃ of conditions, with 16 mesh sieve granulate, adds magnesium stearate, Pulvis Talci mix homogeneously, is the slow-releasing granules of above-mentioned tablet.The gained slow-releasing granules is placed the granulator tabletting.The bag damp-proof membrane, discharging after dry 20 minutes, 40 ℃ of dryings 8 hours are made slow releasing tablet.
Various component content of the present invention is makes 1 content.
Embodiment 4 slow releasing capsule of the present invention
The preparation of slow releasing capsule of the present invention
In proportion active component acetaminophen and ketoprofen are mixed with above-mentioned pharmaceutic adjuvant, gelatinate polymer, by by the equivalent incremental method with the abundant mix homogeneously of active component and adjuvant granulate, dry tabletting, acquisition granule, bead, powder or micro chip; Also can carry out enteric coating to granule, bead, micro chip on demand; Granule, bead, powder or micro chip that above-mentioned steps is made are filled into and promptly make capsule in the capsule
The oral slow-releasing preparation of the present invention that obtains with the foregoing description 3 and 4 carries out release in vitro by standards of pharmacopoeia in the release medium of pH6.8, different time cumulative release percentage rate sees Table 3-4
The subordinate list explanation:
Table 1 is coupling medicine of the present invention result in the experiment of mice acetic acid twisting
Table 2 is the medicinal edema suppression ratio result that on Carrageenan is brought out in mice of coupling of the present invention
Table 3 is the release kilsyth basalt of embodiment 3 preparations of the present invention
Table 4 is the release kilsyth basalt of embodiment 4 preparations of the present invention
The experiment of table 1 mice acetic acid twisting
*Compare with matched group P＜0.01
Compare with acetaminophen or meloxicam+P＜0.05
The edema suppression ratio that on Carrageenan is brought out in table 2 mice
*Compare with matched group P＜0.01
Compare with acetaminophen or ketoprofen+P＜0.05
The device II (paddle board formula) of extracorporeal releasing test in Chinese Pharmacopoeia version drug release determination in 2000 method, 100 rev/mins, simulation enteric liquid, the phosphate buffer of selecting pH6.8 for use is that release medium is measured.The result is as follows for the foregoing description dissolution test:
Table 3 embodiment 3 preparation of Chinese medicine cumulative release percentage ratios
Table 4 embodiment 4 preparation of Chinese medicine cumulative release percentage ratios
Claims (12)
1. oral formulations, it contains acetaminophen and ketoprofen, and the coupling ratio of acetaminophen and ketoprofen is: acetaminophen/ketoprofen is 3.75: 1-15: 1.
2. the oral formulations of claim 1, wherein the coupling ratio of acetaminophen and ketoprofen is: 3.75: 1.
3. claim 1 or 2 oral formulations, it is tablet or capsule.
4. oral slow-releasing preparation, it contains the label and the damp-proof membrane of acetaminophen, ketoprofen, emulsifying agent, slow-release material, lubricant, fluidizer composition, and the coupling ratio of acetaminophen and ketoprofen is: acetaminophen/ketoprofen is 3.75: 1-15: 1.
5. the preparation of claim 4, wherein the coupling ratio of acetaminophen and ketoprofen is: 3.75: 1.
6. as the slow releasing preparation of claim 4 or 5, it is characterized in that: described slow-release material is selected from least a hydroxypropyl emthylcellulose K4M, K15M, K100M, hydroxypropyl cellulose E4M, Cellulose ethyl hydroxypropyl ether, carbomer 934 p, 974p, 971p, hydroxyethyl-cellulose, methylcellulose, xanthan gum, alginate, polyethylene glycol oxide, carboxy vinyl polymer, or the salt of carboxymethyl cellulose, chitosan, binding agent is selected from poly-group ketone 30, ethyl cellulose, lactose, microcrystalline Cellulose or carboxymethyl cellulose, lubricant is selected from least a: magnesium stearate, calcium stearate, Macrogol 4000 or polyethylene glycol 6000, fluidizer are selected from Pulvis Talci or silica gel.
7. as claim 4 or 5 slow releasing preparation, wherein the content of acetaminophen and ketoprofen is the 40-85% of preparation prescription gross weight; Slow-release material is the 6-50% of preparation prescription gross weight, and enteric-coating material is the 6-40% of preparation prescription gross weight.
8. as preparation as described in claim 4 or 5, wherein damp-proof membrane is coating material commonly used, and it consists of Opadry model opadry II, slightly soluble type coating materials, coating weightening finish 2%-6% in accordance with regulations.
9. claim 4 or 5 preparation, wherein said preparation is tablet or capsule.
10. the preparation of claim 9, wherein tablet contains acetaminophen, ketoprofen, lactose, hydroxypropyl emthylcellulose K
15M, carbomer, Pulvis Talci, magnesium stearate, capsule contains acetyl aminophenol, ketoprofen, microcrystalline Cellulose, hydroxypropyl emthylcellulose K
15M, ethyl cellulose, magnesium stearate.
11. uniting of acetaminophen and ketoprofen is used for producing a kind of antiinflammatory, analgesia and antipyretic medicine purposes of being used for, wherein the coupling ratio of acetaminophen and ketoprofen is: acetaminophen/ketoprofen is 3.75: 1-15: 1.
12. the purposes of claim 11, wherein the coupling ratio of acetaminophen and ketoprofen is: acetaminophen/ketoprofen is 3.75: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005101052536A CN1939292B (en) | 2005-09-28 | 2005-09-28 | Oral medicinal preparation and oral slow-releasing preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005101052536A CN1939292B (en) | 2005-09-28 | 2005-09-28 | Oral medicinal preparation and oral slow-releasing preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1939292A CN1939292A (en) | 2007-04-04 |
| CN1939292B true CN1939292B (en) | 2011-01-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2005101052536A Expired - Fee Related CN1939292B (en) | 2005-09-28 | 2005-09-28 | Oral medicinal preparation and oral slow-releasing preparation |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101467997B (en) * | 2007-12-26 | 2010-12-15 | 北京大北农动物保健科技有限责任公司 | Compound medicament composition for animals and uses thereof |
| CN102863350B (en) * | 2011-07-06 | 2015-06-17 | 中国科学院大连化学物理研究所 | Anti-inflammatory analgesia mutual prodrug of non-steroidal antiinflammatory drug and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002100739A4 (en) * | 2002-09-16 | 2002-12-12 | Harry Kypreos | Neuramax |
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2005
- 2005-09-28 CN CN2005101052536A patent/CN1939292B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002100739A4 (en) * | 2002-09-16 | 2002-12-12 | Harry Kypreos | Neuramax |
Non-Patent Citations (2)
| Title |
|---|
| 张宏武等.HPLC同时测定复方布洛芬软胶囊中布洛芬、对乙酰氨基酚的含量.中国药学杂志40 6.2005,40(6),465-467. |
| 张宏武等.HPLC同时测定复方布洛芬软胶囊中布洛芬、对乙酰氨基酚的含量.中国药学杂志40 6.2005,40(6),465-467. * |
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| CN1939292A (en) | 2007-04-04 |
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