WO1997000072A1 - Anti-inflammatory/analgetic composition - Google Patents
Anti-inflammatory/analgetic composition Download PDFInfo
- Publication number
- WO1997000072A1 WO1997000072A1 PCT/JP1996/001614 JP9601614W WO9700072A1 WO 1997000072 A1 WO1997000072 A1 WO 1997000072A1 JP 9601614 W JP9601614 W JP 9601614W WO 9700072 A1 WO9700072 A1 WO 9700072A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ibuprofen
- acetaminophen
- inflammatory
- composition according
- inflammatory analgesic
- Prior art date
Links
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 22
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 34
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 19
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- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 11
- 229960002739 oxaprozin Drugs 0.000 claims abstract description 9
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
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- 238000000034 method Methods 0.000 claims description 10
- 238000013329 compounding Methods 0.000 claims description 5
- 201000009240 nasopharyngitis Diseases 0.000 claims description 3
- 229940124579 cold medicine Drugs 0.000 claims description 2
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- UHSXRTHJCJGEKG-UQKRIMTDSA-N (1s)-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium-6,7-diol;chloride Chemical compound Cl.COC1=C(OC)C(OC)=CC(C[C@H]2C3=CC(O)=C(O)C=C3CCN2)=C1 UHSXRTHJCJGEKG-UQKRIMTDSA-N 0.000 description 1
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- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 description 1
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- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 1
- 229960005174 ambroxol Drugs 0.000 description 1
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
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- 239000000969 carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
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- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
Definitions
- the present invention relates to an anti-inflammatory analgesic composition having enhanced analgesic activity.
- Oxaprozin is widely used as an anti-inflammatory analgesic, but its action is relatively weak, and it is said that it is difficult to obtain a sufficient effect on respiratory diseases.
- the analgesics ibuprofen and acetaminophen are effective for respiratory diseases such as common cold syndrome. Had a problem.
- U.S. Pat. No. 4,552,8999 describes a pharmaceutical composition for treating respiratory diseases such as common cold, which contains anti-inflammatory agents such as ibuprofen and oxabrogine. I have.
- the pharmaceutical composition produces a synergistic effect by combining an anti-inflammatory agent with a sympathomimetic stimulant, an antihistamine, and the like, and does not suggest a synergistic effect due to the combination of the anti-inflammatory agents.
- a pharmaceutical composition containing oxaboxazin and ibubrofen or acetoaminophen Disclosure of the invention
- An object of the present invention is to provide an anti-inflammatory analgesic having an enhanced analgesic effect.
- the present inventors have conducted studies with the aim of enhancing the analgesic effect.
- the combination of oxaprozin with the analgesic agent ibuprofen or acetaminophen provides an anti-inflammatory analgesic with enhanced analgesic action. This has led to the completion of the present invention.
- the present invention includes the following inventions.
- An anti-inflammatory analgesic composition comprising oxasuboral gin and ibubrofen as active ingredients.
- composition according to (2) wherein the mixing ratio (weight ratio) of oxabrozin: ibuprofen is 1: 0.1 to 1:10.
- composition according to (2), wherein the mixing ratio (weight ratio) of oxabrozin: ibuprofen is 0.25 to 1: 5.
- An anti-inflammatory analgesic composition containing oxasubatin and acetoaminophen as active ingredients.
- composition according to (5), wherein the compounding ratio (heavy Mit) of oxaprozin: acetaminophen is 1: 0.1 to 1: 1.
- composition according to the above (5), wherein the mixing ratio (weight ratio) of oxabrozine: acetaminophen is from 1: 0.25 to 1: 5.
- a method for treating a respiratory disease which comprises administering the anti-inflammatory analgesic composition according to the above (1) to a patient with a respiratory disease.
- the mixing ratio (weight ratio) of oxabrozine: ibubrofen or acetoaminophen is usually 1: 0.1-1: 10, preferably 1: 0.25: L: 5.
- the anti-inflammatory analgesic composition of the present invention can usually be orally administered to an adult at 300 to 1600 mg per day as an active ingredient in one or several divided doses. This dose can be appropriately adjusted depending on the age, weight, and medical condition.
- an auxiliary drug such as an antitussive, an anti-inflammatory enzyme, a sympathomimetic, an anti-inflammatory, a drowsiness inhibitor, a vitamin, a crude drug, or an antacid may be appropriately added.
- the anti-inflammatory analgesic composition of the present invention is used as a formulation for oral administration such as tablets, granules, powders, capsules and solutions. These preparations can be prepared by a conventional method.
- Carriers used in the preparation of preparations include excipients such as lactose, starch, sugar, mannitol, crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropyl xymethylcellulose, gelatin, PVP, There are disintegrants such as calcium cellulose cellulose and low-substituted hydroxypropylcellulose, and lubricants such as magnesium stearate, hydrogenated castor oil, and talc. Dyes, flavoring agents and the like can be used.
- No. 2 hard capsule was filled in 200 mg each to obtain 5000 capsules.
- the obtained mixed powder was filled into No. 2 hard capsules in an amount of 20 mg each to obtain 6000 capsules.
- the anti-inflammatory analgesic composition of the present invention has an enhanced analgesic effect as compared to a case where (a) oxabrozine or (b) ibuprofen or acetaminophen is used alone, and includes a power syndrome and the like. Since it has an effect on respiratory diseases, it can be used as a cold remedy. In addition, since a synergistic effect is observed, the effect can be obtained at a low dose, thereby reducing side effects.
Abstract
An anti-inflammatory/analgetic composition which comprises as the active ingredients (a) oxaprozin and (b) ibuprofen or acetaminophen. Compared with cases wherein either (a) oxaprozin or (b) ibuprofen or acetaminophen is employed alone, the composition has an enhanced analgetic effect and is efficacious against respiratory system diseases such as cold syndrome, which makes it usable as a remedy for cold.
Description
明 細 書 Specification
消炎鎮痛薬組成物 技術分野 Anti-inflammatory analgesic composition Technical field
本発明は鎮痛作用の増強された消炎鎮痛薬組成物に関する。 背景技術 The present invention relates to an anti-inflammatory analgesic composition having enhanced analgesic activity. Background art
ォキサブロジン（oxaprozin) は消炎鎮痛薬として広く用いられているが、 作用が比較的弱く呼吸器系疾患に十分な効果を得ることが難しいとされてい る。 一方、 鎮痛薬のイブプロフヱン（ibuprofen) 及びァセトァミノフェン (acetaminophen) はかぜ症候群をはじめとする呼吸器系疾患に対し効果がある 力 副作用も強いため治療効果が十分期待できる量を処方することには問題が めった。 Oxaprozin is widely used as an anti-inflammatory analgesic, but its action is relatively weak, and it is said that it is difficult to obtain a sufficient effect on respiratory diseases. On the other hand, the analgesics ibuprofen and acetaminophen are effective for respiratory diseases such as common cold syndrome. Had a problem.
米国特許第 4， 5 5 2 , 8 9 9号明細書には、 イブプロフェン、 ォキサブロジ ン等の抗炎症剤を配合したかぜ症候群等の呼吸器系疾患を治療するための医薬組 成物力記載されている。 しかしながら、 当該医薬組成物は、 抗炎症剤と交感神経 興奮ァミン、 抗ヒスタミン剤等との組み合わせにより相乗効果をもたらすもので あり、 抗炎症剤同士の配合による相乗効果を示唆するものではない。 また、 その 他の先行技術にもォキサブ口ジンとィブブロフェン又はァセトァミノフェンとを 配合した医薬組成物を開示するものはない。 発明の開示 U.S. Pat. No. 4,552,8999 describes a pharmaceutical composition for treating respiratory diseases such as common cold, which contains anti-inflammatory agents such as ibuprofen and oxabrogine. I have. However, the pharmaceutical composition produces a synergistic effect by combining an anti-inflammatory agent with a sympathomimetic stimulant, an antihistamine, and the like, and does not suggest a synergistic effect due to the combination of the anti-inflammatory agents. Further, there is no other prior art that discloses a pharmaceutical composition containing oxaboxazin and ibubrofen or acetoaminophen. Disclosure of the invention
本発明は、 鎮痛作用が増強された消炎鎮痛薬を提供することを目的とする。 本発明者らは、 鎮痛作用を増強することを目的とし研究した結果、 ォキサプロ ジンに鎮痛薬のィブプロフェン又はァセトァミノフエンを配合することにより、 鎮痛作闬が增強された消炎鎮痛薬が得られることを見いだし、 本発明を完成し た。 An object of the present invention is to provide an anti-inflammatory analgesic having an enhanced analgesic effect. The present inventors have conducted studies with the aim of enhancing the analgesic effect. As a result, the combination of oxaprozin with the analgesic agent ibuprofen or acetaminophen provides an anti-inflammatory analgesic with enhanced analgesic action. This has led to the completion of the present invention.
即ち、 本発明は、 以下の発明を包含する。 That is, the present invention includes the following inventions.
1 . (a) ォキサブロジン及び (b) イブプロフェン又はァセトァミノフェンを有効
成分として含有する消炎鎮痛薬組成物。 1. Effective with (a) oxabrozin and (b) ibuprofen or acetoaminophen An anti-inflammatory analgesic composition containing as an ingredient.
2. ォキサブ口ジン及びィブブロフェンを有効成分として含有する消炎鎮痛薬組 成物。 2. An anti-inflammatory analgesic composition comprising oxasuboral gin and ibubrofen as active ingredients.
3. ォキサブロジン：イブプロフェンの配合比率 （重量比） が 1 ： 0. 1〜1 ： 10である前記 （2) に記載の組成物。 3. The composition according to (2), wherein the mixing ratio (weight ratio) of oxabrozin: ibuprofen is 1: 0.1 to 1:10.
4. ォキサブロジン：イブプロフェンの配合比率 （重量比） 力 : 0. 25〜1 ： 5である前記 （2) に記載の組成物。 4. The composition according to (2), wherein the mixing ratio (weight ratio) of oxabrozin: ibuprofen is 0.25 to 1: 5.
5. ォキサブ口ジン及びァセ卜ァミノフエンを^力成分として含有する消炎鎮痛 薬組成物。 5. An anti-inflammatory analgesic composition containing oxasubatin and acetoaminophen as active ingredients.
6. ォキサプロジン：ァセトァミノフェンの配合比率 （重 Mit)が 1 : 0. 1〜 1 ： 1 ある前記 （5) に記載の組成物。 6. The composition according to (5), wherein the compounding ratio (heavy Mit) of oxaprozin: acetaminophen is 1: 0.1 to 1: 1.
7. ォキサブロジン：ァセ卜ァミノフェンの配合比率 （重量比） 力 1 : 0. 25 〜1 ： 5である前記 （5) に記載の組成物。 7. The composition according to the above (5), wherein the mixing ratio (weight ratio) of oxabrozine: acetaminophen is from 1: 0.25 to 1: 5.
8. 感冒薬として用いる前記 （1) に記載の消炎鎮痛薬組成物。 8. The anti-inflammatory analgesic composition according to the above (1), which is used as a cold medicine.
9. 前記 （1) に記載の消炎鎮痛薬組成物を呼吸器系疾患の患者に投与すること を特徴とする呼吸器系疾患の治療方法。 9. A method for treating a respiratory disease, which comprises administering the anti-inflammatory analgesic composition according to the above (1) to a patient with a respiratory disease.
10. 呼吸器系疾患がかぜ症候群である前記 （9) に記載の方法。 10. The method according to the above (9), wherein the respiratory disease is cold syndrome.
ォキサブロジン：イブブロフェン又はァセトァミノフヱンの配合比率 （重量 比） は通常 1 : 0. 1-1 : 10, 好ましくは 1 : 0. 25〜： L ： 5である。 本発明の消炎鎮痛薬組成物は、 通常、 成人に対して 1日当り有効成分として 300〜1600mgを 1回ないし数回に分けて経口投与することができる。 こ の投与量は年齢、 体重、 病状により適宜増減することができる。 The mixing ratio (weight ratio) of oxabrozine: ibubrofen or acetoaminophen is usually 1: 0.1-1: 10, preferably 1: 0.25: L: 5. The anti-inflammatory analgesic composition of the present invention can usually be orally administered to an adult at 300 to 1600 mg per day as an active ingredient in one or several divided doses. This dose can be appropriately adjusted depending on the age, weight, and medical condition.
また、 必要に応じて、 鎮咳薬、 消炎酵素薬、 交感神経興奮薬、 抗炎症薬、 眠気 防止薬、 ビタミン薬、 生薬、 制酸薬等の補助薬剤を適宜に配合してもよい。 更にまた、 本発明の消炎鎮痛薬組成物は錠剤、 顆粒剤、 散剤、 カプセル剤、 液 剤等の経口投与形態の製剤として用いる。 これらの製剤は、 常法により調製する ことができる。 製剤の調製に使用する担体としては、 乳糖、 デンプン、 砂糖、 マ ンニトール、 結晶セルロース等の賦形剤、 ヒドロキシプロピルセルロース、 ヒド 口キシブ口ピルメチルセルロース、 ゼラチン、 P VP等の結合剤、 カルボキシメ
チルセルロースカルシウム、 低置換度ヒドロキシプロピルセルロース等の崩壊 剤、 ステアリン酸マグネシウム、 硬化ヒマシ油、 タルク等の滑沢剤があり、 この 他必要に応じて溶解補助剤、 緩衝剤、 保存剤、 香料、 色素、 矯味剤等を使用する ことができる。 発明を実施するための最良の形態 If necessary, an auxiliary drug such as an antitussive, an anti-inflammatory enzyme, a sympathomimetic, an anti-inflammatory, a drowsiness inhibitor, a vitamin, a crude drug, or an antacid may be appropriately added. Furthermore, the anti-inflammatory analgesic composition of the present invention is used as a formulation for oral administration such as tablets, granules, powders, capsules and solutions. These preparations can be prepared by a conventional method. Carriers used in the preparation of preparations include excipients such as lactose, starch, sugar, mannitol, crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropyl xymethylcellulose, gelatin, PVP, There are disintegrants such as calcium cellulose cellulose and low-substituted hydroxypropylcellulose, and lubricants such as magnesium stearate, hydrogenated castor oil, and talc. Dyes, flavoring agents and the like can be used. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 実施例及び試験例を挙げ本発明を更に詳しく説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.
実施例 1 Example 1
下記の各成分をそれぞれの分量秤量し均一に混合した後、 得られた混合粉末を After each of the following components is weighed and mixed uniformly, the resulting mixed powder is
2号硬カブセルに 200m gずつ充填し、 カプセル 5000個を得た。 No. 2 hard capsule was filled in 200 mg each to obtain 5000 capsules.
ォキサブロジン 400 g Oxabrozine 400 g
イブプロフェン 450 g 450 g of ibuprofen
乳糖 100 g Lactose 100 g
微結晶セルロース 40 g 40 g microcrystalline cellulose
ステアリン酸マグネシウム 10 g Magnesium stearate 10 g
実施例 2 Example 2
下記の各成分をそれぞれの分量秤量し均一に混合した後、 得られた混合粉末を 2号硬カプセルに 20 Omgずつ充填し、 カプセル 6000個を得た。 After weighing and uniformly mixing the following components, the obtained mixed powder was filled into No. 2 hard capsules in an amount of 20 mg each to obtain 6000 capsules.
ォキサブロジン 400 g Oxabrozine 400 g
イブプロフェン 450 g 450 g of ibuprofen
塩化リゾチーム 90 g (力価） Lysozyme chloride 90 g (titer)
乳糖 170 g Lactose 170 g
微結晶セルロース 80 g 80 g microcrystalline cellulose
ステアリン酸マグネシウム 10 g Magnesium stearate 10 g
実施例 3 Example 3
下記の各成分をそれぞれの分量秤量し均一に混合した後、 得られた混合粉末を 直打法により 1錠重量 200mgになるように打錠し、 錠剤 10000個を得 た。 After weighing each of the following components and mixing them uniformly, the resulting mixed powder was tableted by a direct compression method so that each tablet weighed 200 mg to obtain 10,000 tablets.
ォキサプロジン 400 g
ァセトァミノフェン 900 g 400 g of oxaprozin Acetaminophen 900 g
塩酸ァンブロキソール（ambroxol) 45 g Ambroxol hydrochloride (ambroxol) 45 g
塩ィヒリゾチーム 90 g (力価） 90 g of salted lysozyme (titer)
乳糖 300 g Lactose 300 g
低置換度ヒドロキシ Low substituted hydroxy
プロピルセルロース 245 g Propyl cellulose 245 g
ステアリン酸マグネシウム 10 g Magnesium stearate 10 g
硬化ヒマシ油 10 g Hardened castor oil 10 g
実施例 4 Example 4
下記の各成分をそれぞれの分量秤量し均一に混合した後、 実施例 3に準拠し 0 Om gの錠剤 7000個を得た。 After weighing each of the following components and uniformly mixing them, 7000 tablets of 0 Omg were obtained according to Example 3.
ォキサプロジン 600 g Oxaprozin 600 g
ィブブロフェン 450 g Ibubrofen 450 g
リン酸ジヒドロコディン 24g 24g dihydrocodine phosphate
メキタジン (tnequitazine) 6 g 6 g of mequitazine
塩酸アンブロキソール 45 g Ambroxol hydrochloride 45 g
塩化リゾチーム 90 g (力価） Lysozyme chloride 90 g (titer)
d 1一塩酸メチルエフエドリン 60 g d 1 Methylefedrine monohydrochloride 60 g
？し 400 g ? 400 g
微結晶セルロース 395 g Microcrystalline cellulose 395 g
ステアリン酸マグネシウム 15 g Magnesium stearate 15 g
硬化ヒマシ油 15 g Hardened castor oil 15 g
実施例 5 Example 5
下記の各成分をそれぞれの分量秤量し均一に混合した後、 実施例 3に準拠し 0 Omgの錠剤 7000個を得た。 After the following components were weighed and mixed uniformly, 7000 tablets of 0 mg were obtained according to Example 3.
ォキサプロジン 400 g 400 g of oxaprozin
イブプロフェン 225 g Ibuprofen 225 g
ァセトァミノフェン 450 g Acetaminophen 450 g
ノス力ピン (noscapine) 48 g
リン酸ジヒドロコディン 24 g Noscapine 48 g 24 g of dihydrocodine phosphate
メキタジン 6 g Mequitadine 6 g
塩酸アンブロキソール 45 g Ambroxol hydrochloride 45 g
塩化リゾチーム 90 g (力価） Lysozyme chloride 90 g (titer)
塩酸トリメトキノ一ル (trimetoquinol) 6 g 6 g of trimetoquinol hydrochloride
無水カフエイン 75 g 75 g anhydrous caffeine
ビタミン 硝酸塩 8 g Vitamin nitrate 8 g
ビタミン B 2 4 g Vitamin B 2 4 g
乳糖 350 g Lactose 350 g
微結晶セルロース 339 g 339 g microcrystalline cellulose
ステアリン酸マグネシウム 1 5 g Magnesium stearate 15 g
硬化ヒマシ油 1 5 g Hardened castor oil 15 g
試験例 1 マウスでの鎮痛作用 （酢酸 writhing法） Test Example 1 Analgesic effect in mice (acetic acid writhing method)
4週齢の ddY系雄性マウスを 1群 1 0匹用い、 Kosterらの方法 ( oster R. , Anderson M. and De Beer E. J Fed. Proc, 18, 412 (1958) )に準じ、 各薬物 経口投与 30分後に 0. 7%酢酸を 0. lmlZl 0 g腹腔内に投与し、 酢酸投 与 1 0分後より 1 0分間の writhing数を測定した。 対照群には 5%アラビアゴム 水溶液を経口投与して、 同様に測定した。 結果を表 1に示した。 Using 4-week-old ddY male mice of 10 mice per group, each drug was used according to the method of Koster et al. (Oster R., Anderson M. and De Beer E. J Fed. Proc, 18, 412 (1958)). Thirty minutes after oral administration, 0.7% acetic acid was intraperitoneally administered with 0. lmlZl 0 g, and the number of writhings was measured for 10 minutes from 10 minutes after administration of acetic acid. A 5% aqueous solution of gum arabic was orally administered to the control group, and the same measurement was performed. The results are shown in Table 1.
表 1 E D s。値の比較 （酢酸 writhing法） 薬 物 E DBO mg/kg,p.o. (95¾ し 才キサプロジン 45. 0 ( 18.0—112.2) Table 1 EDs. Comparison of values (acetic acid writhing method) Drug E DBO mg / kg, p.o. (95¾-year-old xaprozin 45.0 (18.0—112.2)
ァセ卜ァミノフェン 300. 0 (173.5 518.6) Acetaminophen 300.0 (173.5 518.6)
イブプロフヱン 1 22.- 3 ( 78.7 190.1) 才キサプロジン + ァセトァミノフェン (1:2) 2 8. 2 ( 12.6— 85.2) Ibuprofen 1 22.- 3 (78.7 190.1) year old xaprozin + acetaminophen (1: 2) 28.2 (12.6—85.2)
才キサプロジ + イブプロフェン (1:1.2) 2 2. 8 ( 10.2— 72.4) 表 1に示したように、 ォキサプロジン単独の場合に比べ、 ォキサブロジンとァ セトァミノフェンの組み合わせでは約 1. 60倍、 ォキサブロジンとイブプロ フェンの組み合わせでは約 1. 97倍の効力の増強がみられた。
試験例 2 ラツ卜での鎮痛作用 （Randall and Selitto法） Sixaprodi + ibuprofen (1: 1.2) 22.8 (10.2-72.4) The combination showed an approximately 1.97-fold increase in potency. Test example 2 Analgesic effect on rat (Randall and Selitto method)
4週齢の Wistar系雄性ラッ 卜を 1群 6〜1 2匹用い、 analges meter (Ugo Basile) を使用して検討した。 Four-week-old male Wistar rats were examined using an analges meter (Ugo Basile) using 6 to 12 mice per group.
1時間間隔で力ラゲニン水溶液を 2回右後肢足餹皮下に注入し、 その 2時間後 に各薬物を経口投与して 1時間ごとに 4時間後まで、 左 （正常足） 右 （炎症足） 後肢の疼痛閾値を測定した。 対照群には 5 %アラビアゴム溶液を経口投与して、 同様に測定した。 吉果を表 2に示した。 Inject the aqueous solution of force lagenin twice subcutaneously into the right hind paw at 1 hour intervals, and orally administer each drug 2 hours after that, up to 4 hours after each hour until left (normal foot) right (inflamed foot) Hind limb pain threshold was measured. The control group was orally administered with a 5% gum arabic solution and measured similarly. Yoshika is shown in Table 2.
表 2 ED5。値の比較 (Randall and Selitto法） 薬 物 E DBO mg/kg,p.o. (95¾C.し ォキサブロジン 1 7 3. 5 ( 91.3—329.6) Table 2 ED 5. Comparison of values (Randall and Selitto method) Drug E DBO mg / kg, po (95 ° C. Oxaxabrozine 1 73.5 (91.3-329.6)
ァセトァミノフェン 3 2 5. 0 (190.2—543.8) Acetaminophen 3 25.0 (190.2-543.8)
イブプロフェン 97 8 ( 58.7〜190· 1) 才キサプロジン + ァセトァミノフェン (1:2) 07. 7 ( 68· 5〜216.2) Ibuprofen 97 8 (58.7 to 1901) year old xaprozin + acetaminophen (1: 2) 07.7 (685 to 216.2)
才キサブロジン + イブプロフェン (1:1.2) 69. 8 ( 28.6—128.4) 表 2に示したように、 才キサブロジン単独の場合に比べ、 ォキサブロジンと ァセトァミノフェンの組み合わせでは約 1. 61倍、 ォキサブロジンとイブプロ フェンの組み合わせでは約 2. 49倍の効力の増強がみられた。 産業上の利用の可能性 As shown in Table 2, the combination of oxabrozine and acetaminophen is approximately 1.61 times higher than that of oxabrozine alone, compared to the case of oxabrozine alone. The combination of ibuprofen showed about a 2.49-fold increase in potency. Industrial applicability
本発明の消炎鎮痛薬組成物は、 （a) ォキサブロジン又は (b) イブプロフヱン又 はァセトァミノフエンをそれぞれ単独で使用した場合に比べ、 鎮痛作用が増強さ れており、 力 症候群をはじめとする呼吸器系疾患に対し効果を有するため、 感 冒薬として用いることができる。 また、 相乗効果が認められることから、 低用量 で効果が得られるので、 副作用も低減できる。
The anti-inflammatory analgesic composition of the present invention has an enhanced analgesic effect as compared to a case where (a) oxabrozine or (b) ibuprofen or acetaminophen is used alone, and includes a power syndrome and the like. Since it has an effect on respiratory diseases, it can be used as a cold remedy. In addition, since a synergistic effect is observed, the effect can be obtained at a low dose, thereby reducing side effects.
Claims
1 . (a) ォキサブロジン及び (b) イブプロフヱン又はァセトァミノフェンを 力 成分として含有する消炎鎮痛薬組成物。 1. An anti-inflammatory analgesic composition comprising (a) oxabrozin and (b) ibuprofen or acetaminophen as active ingredients.
2 . ォキサブ口ジン及びィブブロフェンを有効成分として含有する消炎鎮痛薬組 成物。 2. An anti-inflammatory analgesic composition containing oxasuboral gin and ibubrofen as active ingredients.
3 . ォキサプロジン：イブプロフェンの配合比率 （重量比） 力 s' l ： 0 . 1〜1 ： 1 0である請求の範囲第 2項記載の組成物。 3. The composition according to claim 2, wherein the compounding ratio (weight ratio) of oxaprozin: ibuprofen is s'l: 0.1 to 1:10.
4 . ォキサブロジン：イブプロフェンの配合比率 （重量比） 力 s' l ： 0 . 2 5〜1 ： 5である請求の範囲第 2項記載の組成物。 4. The composition according to claim 2, wherein the compounding ratio (weight ratio) of oxabrozine: ibuprofen is s'l: 0.25 to 1: 5.
5 . ォキ'サブ口ジン及びァセトァミノフエンを有効成分として含有する消炎鎮痛 薬組成物。 5. An anti-inflammatory analgesic composition comprising oki's sub mouth gin and acetoaminophen as active ingredients.
6 . ォキサブロジン：ァセトァミノフェンの配合比率 （重量比） が 1 : 0 . 1〜 1 ： 1 0である請求の範囲第 5項記載の組成物。 6. The composition according to claim 5, wherein the compounding ratio (weight ratio) of oxabrozine: acetaminophen is 1: 0.1 to 1:10.
7. ォキサブ口ジン：ァセトァミノフエンの配合比率 （重量比） が 1 ： 0 . 2 5 〜1 ： 5である請求の範囲第 5項記載の組成物。 7. The composition according to claim 5, wherein the compounding ratio (weight ratio) of oxazine gin: acetaminophen is from 1: 0.25 to 1: 5.
8 . 感冒薬として用いる請求の範囲第 1項記載の消炎鎮痛薬組成物。 8. The anti-inflammatory analgesic composition according to claim 1, which is used as a common cold medicine.
9 . 請求の範囲第 1項記載の消炎鎮痛薬組成物を呼吸器系疾患の患者に投与する ことを特徵とする呼吸器系疾患の治療方法。 9. A method for treating a respiratory disease, which comprises administering the anti-inflammatory analgesic composition according to claim 1 to a patient with a respiratory disease.
10. 呼吸器系疾患がかぜ症候群である請求の範囲第 9項記載の方法。
10. The method according to claim 9, wherein the respiratory disease is cold syndrome.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU60160/96A AU6016096A (en) | 1995-06-16 | 1996-06-13 | Anti-inflammatory/analgetic composition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14982195 | 1995-06-16 | ||
| JP7/149821 | 1995-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997000072A1 true WO1997000072A1 (en) | 1997-01-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1996/001614 WO1997000072A1 (en) | 1995-06-16 | 1996-06-13 | Anti-inflammatory/analgetic composition |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU6016096A (en) |
| WO (1) | WO1997000072A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010089913A (en) * | 2000-03-13 | 2001-10-17 | 류영선 | The chemical-free new materials for toy and it`s manufacturing method |
-
1996
- 1996-06-13 WO PCT/JP1996/001614 patent/WO1997000072A1/en active Application Filing
- 1996-06-13 AU AU60160/96A patent/AU6016096A/en not_active Abandoned
Non-Patent Citations (2)
| Title |
|---|
| BY THE PHARMACIST SOCIETY OF OSAKA HOSPITAL, "Drug Handbook (5th Edit.)", YAKUGYO JIHOSHA CO., LTD., 5 February 1995, p. 126-127, 108-109, 94-95. * |
| THE MERCK INDEX, Eleventh Edition (1989) p. 6880, 4811, 39. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010089913A (en) * | 2000-03-13 | 2001-10-17 | 류영선 | The chemical-free new materials for toy and it`s manufacturing method |
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| Publication number | Publication date |
|---|---|
| AU6016096A (en) | 1997-01-15 |
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