JP4695326B2 - Pharmaceutical composition for rhinitis - Google Patents
Pharmaceutical composition for rhinitis Download PDFInfo
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- JP4695326B2 JP4695326B2 JP2002364645A JP2002364645A JP4695326B2 JP 4695326 B2 JP4695326 B2 JP 4695326B2 JP 2002364645 A JP2002364645 A JP 2002364645A JP 2002364645 A JP2002364645 A JP 2002364645A JP 4695326 B2 JP4695326 B2 JP 4695326B2
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- hydrochloride
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- pseudoephedrine
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Description
【0001】
【発明の属する技術分野】
本発明は、プソイドエフェドリンと、ハロゲン化イソプロパミド、アンブロキソール及び/又はフェニレフリン、を含有する医薬組成物(特に、鼻炎、又は、くしゃみ若しくは鼻水の抑制に用いるもの)に関する。
【0002】
【従来の技術】
花粉症などのアレルギー性鼻炎や、感冒などの鼻炎症状に用いられる鼻炎用内服薬には、鼻粘膜充血除去を目的とした交感神経興奮薬、鼻水を抑えるための副交感神経遮断薬、等が配合されることがある(例えば、非特許文献1参照)。
【0003】
本発明に関わる公知の配合又は併用として以下のものが挙げられる。
即ち、
1)交感神経興奮薬を2種併用した例として、塩酸フェニレフリンと塩酸フェニルプロパノールアミンとの配合(例えば、非特許文献2参照)、
2)交感神経興奮薬と副交感神経遮断薬を併用した例として、塩酸メチルエフェドリンとヨウ化イソプロパミドとの配合(例えば、非特許文献3参照)、
3)交感神経興奮薬のプソイドエフェドリンと去痰薬の臭化水素酸デキストロメトルファン又はグアイフェネシンとの配合(例えば、非特許文献4参照)である。
【0004】
しかしながら、これらの併用により鼻炎症状が相乗的に改善されたという報告は存在しない。又、これまで、交感神経興奮薬のプソイドエフェドリンとの併用薬として、副交感神経遮断薬のハロゲン化イソプロパミド、去痰薬のアンブロキソール及び/又は交感神経興奮薬のフェニレフリン、を用いた医薬は知られていない。
【0005】
【非特許文献1】
一般用医薬品製造[輸入]承認基準,2000,じほう、
【非特許文献2】
JAPIC編、一般薬 日本医薬品集, 2002, じほう、723ページ
【非特許文献3】
JAPIC編、一般薬 日本医薬品集,2002,じほう、62ページ
【非特許文献4】
Allen, L. V. et al. Ed. Handbook of Nonprescription Drugs, 12th edition, American Pharmaceutical Association、183ページのTable9-2
【0006】
【発明が解決しようとする課題】
本発明者等は、鼻炎、くしゃみ及び鼻水の抑制に用いることのできる医薬につき、種々の薬剤を検討した。その結果、意外にも、プソイドエフェドリンに対して、ハロゲン化イソプロパミド、アンブロキソール及び/又はフェニレフリンのを配合した組成物が、各成分を単独に配合した場合と比較して顕著な効果を有し、前記症状に有効であることを見出して、本発明を完成させた。
【0007】
【課題を解決するための手段】
本発明は、
1)プソイドエフェドリンとハロゲン化イソプロパミド、アンブロキソール及び/又はフェニレフリンを含有する医薬組成物であり、
好適には、
2)プソイドエフェドリン及びハロゲン化イソプロパミドを含有する医薬組成物であり、
3)プソイドエフェドリン及びヨウ化イソプロパミドを含有する医薬組成物であり、
4)プソイドエフェドリン及びアンブロキソールを含有する医薬組成物であり、
5)プソイドエフェドリン及びフェニレフリンを含有する医薬組成物である。
【0008】
上記医薬において好適には、鼻炎、くしゃみの抑制又は鼻水の抑制に用いることを特徴とする医薬組成物である。
【0009】
本発明において、含有される各成分は、薬理学上許容される塩として含有されていても良く、そのような塩としては、
成分が塩基性官能基を持つ場合には、例えばフッ化水素酸塩、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩のようなハロゲン化水素酸塩;硝酸塩、過塩素酸塩、硫酸塩、リン酸塩等の無機酸塩;メタンスルホン酸塩、トリフルオロメタンスルホン酸塩、エタンスルホン酸塩のような低級有機スルホン酸塩;ベンゼンスルホン酸塩、p-トルエンスルホン酸塩等のようなアリールスルホン酸塩;オルニチン酸塩、グルタミン酸塩のようなアミノ酸塩;及びフマル酸、コハク酸、クエン酸、酒石酸、シュウ酸、マレイン酸のようなカルボン酸塩を挙げることができ、
成分が酸性官能基をもつ場合には、ナトリウム塩、カリウム塩、リチウム塩のようなアルカリ金属塩、カルシウム塩、マグネシウム塩のようなアルカリ土類金属塩、アルミニウム塩、鉄塩、亜鉛塩、銅塩、ニッケル塩、コバルト塩等の金属塩;アンモニウム塩のような無機塩、t−オクチルアミン塩、ジベンジルアミン塩、モルホリン塩、グルコサミン塩、フェニルグリシンアルキルエステル塩、エチレンジアミン塩、N−メチルグルカミン塩、グアニジン塩、ジエチルアミン塩、トリエチルアミン塩、ジシクロヘキシルアミン塩、N,N’−ジベンジルエチレンジアミン塩、クロロプロカイン塩、プロカイン塩、ジエタノールアミン塩、N−ベンジル−フェネチルアミン塩、ピペラジン塩、テトラメチルアンモニウム塩、トリス(ヒドロキシメチル)アミノメタン塩のような有機塩等のアミン塩を挙げる事ができ、プソイドエフェドリンの場合、好適には塩酸塩又は硫酸塩であり、アンブロキソールの場合、塩酸塩であり、フェニレフリンの場合、好適には塩酸塩である。
【0010】
また、ハロゲン化イソプロパミドの場合、好適には臭化イソプロパミド又はヨウ化イソプロパミドが挙げられ、特に好適にはヨウ化イソプロパミドが挙げられる。
【0011】
【発明の実施の形態】
プソイドエフェドリンはUSP(米国薬局方)XXIVに収載されており、塩酸フェニレフリンは日本薬局方XIVに収載されている。また、塩酸アンブロキソールおよびハロゲン化イソプロパミドのうちヨウ化イソプロパミドについては医薬品として市販されており、前者は(株)ワイ・アイ・シー(日本)より、後者はProcos S.P.A(イタリア)より容易に入手し得る。
【0012】
本発明の抗鼻炎用薬が固形製剤の場合において含有される、プソイドエフェドリンの重量%は通常、0.01乃至50%であり、好適には、0.1乃至30%であり、ハロゲン化イソプロパミドの重量%は通常、0.0005乃至2%であり、好適には、0.004乃至1%であり、また、アンブロキソールの重量%は通常、0.003乃至13%であり、好適には、0.03乃至8%であり、さらにまた、フェニレフリンの重量%は通常、0.002乃至8%であり、好適には、0.02乃至5%である。
【0013】
本発明の抗鼻炎用薬が液剤の場合において含有される、プソイドエフェドリンの含有量は通常、0.1乃至200mg/mLであり、好適には、1.0乃至100mg/mLであり、ハロゲン化イソプロパミドの含有量は通常、0.0005乃至4mg/mLであり、好適には、0.004乃至2mg/mLであり、また、アンブロキソールの含有量は通常、0.003乃至25mg/mLであり、好適には、0.03乃至13mg/mLであり、さらにまた、フェニレフリンの含有量は通常、0.002乃至16mg/mLであり、好適には、0.02乃至8mg/mLである。
【0014】
本発明においては、上記有効成分の他、必要に応じて抗ヒスタミン薬、抗炎症薬、カフェイン類、ビタミン類、生薬などを本発明の効果を損なわない範囲で配合することができる。
【0015】
本発明の抗鼻炎用薬の具体的な剤形としては、例えば、錠剤、細粒剤(散剤を含む)、カプセル、液剤(シロップ剤を含む)等をあげることができ、各剤形に適した添加剤や基材を適宜使用し、日本薬局方等に記載された通常の方法に従い、製造することができる。
【0016】
上記各剤形において、その剤形に応じ、通常使用される各種添加剤を使用することもできる。
【0017】
例えば、錠剤の場合、乳糖、結晶セルロース等を賦形剤として、メタケイ酸アルミン酸マグネシウム又は酸化マグネシウム等を安定化剤として、ヒドロキシプロピルセルロース等をコーテイング剤として、ステアリン酸マグネシウム等を滑沢剤として、使用することができ、
細粒剤及びカプセル剤の場合、乳糖、精製白糖等を賦形剤として、メタケイ酸アルミン酸マグネシウム又は酸化マグネシウム等を安定化剤として、トウモロコシデンプン等を吸着剤として、ヒドロキシプロピルセルロース等を結合剤として、使用することができる。
【0018】
上記各剤形において、必要に応じ、クロスポピドン等の崩壊剤;ポリソルベート等の界面活性剤;ケイ酸カルシウム等の吸着剤;三二酸化鉄、カラメル等の着色剤;安息香酸ナトリウム等の安定剤;pH調節剤;香料;等を添加することもできる。
【0019】
本発明における組成物を投与する際は、組成物のそれぞれの成分を同時に、又は、時間をおいて別々に投与することが出来る。
【0020】
上記の「同時に」投与するとは、ほぼ同じ時間に投与できる投与形態であれば特に限定はないが、単一の組成物として投与するのが好ましい。
【0021】
また上記の「時間をおいて別々に」投与するとは、異なった時間に別々に投与できる投与形態であれば特に限定はないが、例えば、1の成分を投与し、次いで、決められた時間後に、他の成分を投与する方法が挙げられる。
【0022】
また、投与する組成物の成分が、合わせて3種以上ある場合には、「同時に、又は、時間を置いて別々に」投与するとは、それらの全てを同時に投与する方法、各々時間を置いて別々に投与する方法、2種以上を同時に投与し時間を置いて残りの薬剤を投与する方法、又は、2種以上を時間を置いて投与して、残りの薬剤を同時に投与する方法等を含む。
【0023】
【実施例】
以下に、実施例等を示し、本発明をさらに詳細に説明するが、本発明はこれらに限定されるものではない。
(実施例1)錠剤
(1)成分
【0024】
【表1】
(2)製法
上記成分及び分量をとり、日局製剤総則「錠剤」の項に準じて錠剤を製する。(実施例2)細粒剤
(1)成分
【0025】
【表2】
(2)製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製する。
実施例(3)カプセル剤
(1)成分
【0026】
【表3】
(2)製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製した後、カプセルに充てんして硬カプセル剤を製する。
実施例(4)シロップ剤
(1)成分
【0027】
【表4】
(2)製法
上記成分及び分量をとり、日局製剤総則「シロップ剤」の項に準じてシロップ剤を製した後、褐色ガラス瓶に充てんしてシロップ剤を製する。
試験例( 1 )抗原刺激に対するくしゃみの抑制効果
(1)被験物質
被験物質は、試験当日に0.5%トラガント液で懸濁液にして用いた。被験物質の投与液量は、体重1Kgあたり2.0mLとし、対照群には同量の0.5%トラガント液を投与した。
(2)試験動物
Hartley系雄性モルモット5週齢(日本SLC社より購入)を、温度20〜26℃、湿度35〜65%の環境制御飼育装置(日本クレア製)で、固型飼料および水道水を与え、照明時間7:00〜19:00の条件下で、予備飼育後に使用した。
(3)試験方法
▲1▼能動感作モルモットの作製
6週齢のモルモットの背部皮下と腹腔内に抗原液(卵白アルブミン50mg/mL:シグマ化学製)を0.5mLずつ投与して免疫する。1週間後、同量の抗原を同様に投与して追加免疫を施す。追加免疫の7〜9日後、約24時間絶食し、能動感作モルモットとして試験に供する。
▲2▼抗原によるくしゃみの誘発
感作動物の健康状態を点検して選抜後、1群5匹の体重が平均化するように振り分ける。次いで、モルモットの両側鼻腔内に抗原液(50mg/mL)を0.1mLずつ点鼻する。以後15分間の症状観察を行い、くしゃみの回数を計測して、抗原誘発性鼻症状の強度とする。
▲3▼被験物質の抑制作用
被験物質は経口ゾンデを用いて、前項▲2▼の抗原点鼻1時間前に投与する。くしゃみの抑制率(%)はいずれも下式より算出する。
【0028】
抑制率(%)=[1−被験物質投与群のくしゃみ平均回数/対照群のくしゃみ平均回数]×100
(4)試験結果
塩酸プソイドエフェドリン[P(mg/Kg)]とヨウ化イソプロパミド[I(mg/Kg)]の各単剤および組合せにおけるくしゃみ抑制率の結果を表5に示す。
【0029】
【表5】
塩酸プソイドエフェドリンとヨウ化イソプロパミドを組み合わせることにより、優れたくしゃみ抑制効果を示した。
塩酸プソイドエフェドリン[P(mg/Kg)]と塩酸アンブロキソール[A(mg/Kg)]の各単剤および組合せにおけるくしゃみ抑制率の結果を表6に示す。
【0030】
【表6】
塩酸プソイドエフェドリンと塩酸アンブロキソールを組み合わせることにより、優れたくしゃみ抑制効果を示した。
塩酸プソイドエフェドリン[P(mg/Kg)]と塩酸フェニレフリン[F(mg/Kg)]の各単剤および組合せにおけるくしゃみ抑制率の結果を表7に示す。
【0031】
【表7】
塩酸プソイドエフェドリンと塩酸フェニレフリンを組み合わせることにより、優れたくしゃみ抑制効果の改善を示した。
【0032】
【発明の効果】
本発明のプソイドエフェドリンと、ハロゲン化イソプロパミド、アンブロキソール及び/又はフェニレフリンと、を含有する医薬(特に、鼻炎、又はくしゃみ若しくは鼻水の抑制に用いるもの)は顕著な効果を示し、医薬として有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a pharmaceutical composition containing pseudoephedrine and halogenated isopropamide, ambroxol and / or phenylephrine (especially used for the control of rhinitis or sneezing or runny nose).
[0002]
[Prior art]
Internal medicines for rhinitis used for allergic rhinitis such as hay fever and nasal inflammation such as colds are combined with sympathomimetic drugs for removing nasal mucosal hyperemia, parasympathomimetic drugs for suppressing runny nose, etc. (See, for example, Non-Patent Document 1).
[0003]
The following are mentioned as well-known mixing | blending or combined use in connection with this invention.
That is,
1) As an example of using two kinds of sympathomimetic drugs in combination, a combination of phenylephrine hydrochloride and phenylpropanolamine hydrochloride (for example, see Non-Patent Document 2),
2) As an example of a combination of a sympathomimetic drug and a parasympathetic nerve blocker, a combination of methylephedrine hydrochloride and isopropamide iodide (for example, see Non-Patent Document 3),
3) A combination of pseudoephedrine as a sympathomimetic drug and dextromethorphan hydrobromide or guaifenesin as an expectorant (see, for example, Non-Patent Document 4).
[0004]
However, there is no report that nasal inflammation was synergistically improved by these combinations. In addition, as a concomitant drug with pseudoephedrine, a sympathomimetic drug, a drug using a parasympatholytic agent halogenated isopropamide, an expectorant ambroxol and / or a sympathomimetic drug phenylephrine has been known. Absent.
[0005]
[Non-Patent Document 1]
OTC Drug Manufacturing [Import] Approval Standard, 2000, Jiho,
[Non-Patent Document 2]
JAPIC, General Medicine Japan Pharmaceuticals, 2002, Jiho, p. 723 [Non-patent Document 3]
JAPIC, General Medicine Japan Pharmaceuticals, 2002, Jiho, p. 62 [Non-Patent Document 4]
Allen, LV et al. Ed. Handbook of Nonprescription Drugs, 12th edition, American Pharmaceutical Association, page 183, Table 9-2
[0006]
[Problems to be solved by the invention]
The inventors of the present invention have studied various drugs for pharmaceuticals that can be used for suppression of rhinitis, sneezing and runny nose. As a result, surprisingly, a composition in which halogenated isopropamide, ambroxol and / or phenylephrine is blended with pseudoephedrine has a remarkable effect as compared with the case where each component is blended alone, The present invention was completed by finding it effective for the above symptoms.
[0007]
[Means for Solving the Problems]
The present invention
1) A pharmaceutical composition comprising pseudoephedrine and halogenated isopropamide, ambroxol and / or phenylephrine,
Preferably,
2) A pharmaceutical composition containing pseudoephedrine and halogenated isopropamide,
3) A pharmaceutical composition containing pseudoephedrine and isopropamide iodide,
4) A pharmaceutical composition comprising pseudoephedrine and ambroxol,
5) A pharmaceutical composition containing pseudoephedrine and phenylephrine.
[0008]
The pharmaceutical composition is preferably used for rhinitis, sneezing or nasal discharge.
[0009]
In the present invention, each component contained may be contained as a pharmacologically acceptable salt, and as such a salt,
When the component has a basic functional group, for example, a hydrohalide such as hydrofluoride, hydrochloride, hydrobromide, hydroiodide; nitrate, perchlorate, sulfuric acid Inorganic acid salts such as salts and phosphates; lower organic sulfonates such as methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; such as benzenesulfonate and p-toluenesulfonate Aryl sulfonates; amino acid salts such as ornithate, glutamate; and carboxylates such as fumaric acid, succinic acid, citric acid, tartaric acid, oxalic acid, maleic acid,
When the component has an acidic functional group, alkali metal salt such as sodium salt, potassium salt and lithium salt, alkaline earth metal salt such as calcium salt and magnesium salt, aluminum salt, iron salt, zinc salt, copper Metal salts such as salts, nickel salts and cobalt salts; inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N-methylglu Camin salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-phenethylamine salt, piperazine salt, tetramethylammonium salt , Tris (hydroxy Examples thereof include amine salts such as organic salts such as methyl) aminomethane salt. In the case of pseudoephedrine, it is preferably hydrochloride or sulfate, in the case of ambroxol, it is hydrochloride, and in the case of phenylephrine, Preferred is the hydrochloride.
[0010]
In the case of a halogenated isopropamide, preferred are brominated isopropamide and iodopropamide, and particularly preferred is iodoisopropamide.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
Pseudoephedrine is listed in USP (United States Pharmacopoeia) XXIV, and phenylephrine hydrochloride is listed in Japanese Pharmacopoeia XIV. Of the ambroxol hydrochloride and halogenated isopropamide, the isopropamide iodide is commercially available. The former is readily available from YIC (Japan) and the latter from Procos SPA (Italy). Can do.
[0012]
The weight% of pseudoephedrine contained when the antirhinitis drug of the present invention is a solid preparation is usually 0.01 to 50%, preferably 0.1 to 30%. The weight percentage is usually 0.0005 to 2%, preferably 0.004 to 1%, and the weight percentage of ambroxol is usually 0.003 to 13%, preferably 0.03% to 8%, and the weight percent of phenylephrine is usually 0.002 to 8%, preferably 0.02 to 5%.
[0013]
The content of pseudoephedrine contained when the antirhinitis drug of the present invention is a liquid is usually 0.1 to 200 mg / mL, preferably 1.0 to 100 mg / mL, and halogenated isopropamide. The content of is usually 0.0005 to 4 mg / mL, preferably 0.004 to 2 mg / mL, and the content of ambroxol is usually 0.003 to 25 mg / mL. The content of phenylephrine is usually 0.002 to 16 mg / mL, and preferably 0.02 to 8 mg / mL.
[0014]
In the present invention, in addition to the above active ingredients, antihistamines, anti-inflammatory drugs, caffeine, vitamins, herbal medicines and the like can be blended as necessary, as long as the effects of the present invention are not impaired.
[0015]
Specific dosage forms of the anti-rhinitis drug of the present invention include, for example, tablets, fine granules (including powders), capsules, liquids (including syrups) and the like, and are suitable for each dosage form. It can be produced according to the usual methods described in the Japanese Pharmacopoeia using appropriate additives and base materials.
[0016]
In the above dosage forms, various commonly used additives can be used depending on the dosage form.
[0017]
For example, in the case of tablets, lactose, crystalline cellulose or the like as an excipient, magnesium aluminate or magnesium oxide as a stabilizer, hydroxypropyl cellulose or the like as a coating agent, magnesium stearate or the like as a lubricant Can be used,
In the case of fine granules and capsules, lactose, refined sucrose, etc. are used as excipients, magnesium metasilicate aluminate or magnesium oxide as stabilizers, corn starch etc. as adsorbents, hydroxypropylcellulose etc. as binders As can be used.
[0018]
In each of the above dosage forms, a disintegrant such as crospovidone; a surfactant such as polysorbate; an adsorbent such as calcium silicate; a colorant such as iron sesquioxide and caramel; a stabilizer such as sodium benzoate; A pH adjuster; a fragrance, etc. can also be added.
[0019]
When the composition in the present invention is administered, each component of the composition can be administered simultaneously or separately with time.
[0020]
The “simultaneous” administration is not particularly limited as long as it can be administered at substantially the same time, but it is preferably administered as a single composition.
[0021]
In addition, the administration “separately at a time” is not particularly limited as long as it can be administered separately at different times. For example, one component is administered, and then, after a predetermined time The method of administering another component is mentioned.
[0022]
In addition, when there are three or more components in the composition to be administered, “simultaneously or separately with time” means that all of them are administered at the same time, each with time. Includes a method of administration separately, a method of administering two or more at the same time and administering the remaining drug at a time, a method of administering two or more at a time and administering the remaining drug at the same time, etc. .
[0023]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples and the like, but the present invention is not limited thereto.
Example 1 Tablet (1) Ingredients
[Table 1]
(2) Manufacturing method Take the above ingredients and the amount, and manufacture the tablet according to the section of the General Rules for Pharmaceutical Preparations “Tablet”. (Example 2) Fine granule (1) component
[Table 2]
(2) Production method Take the above ingredients and quantities, and produce a fine granule according to the section “Granule” of the General Rules for Preparations.
Example (3) Capsule (1) Ingredient
[Table 3]
(2) Manufacturing method After taking the above components and the amount, and making a fine granule according to the section of the Japanese Pharmacopoeia General Rules “Granule”, the capsule is filled into a hard capsule.
Example (4) Syrup (1) Ingredient
[Table 4]
(2) Manufacturing method Take the above components and quantities, and make a syrup according to the Japanese general formulation “Syrup” section, then fill it into a brown glass bottle to make a syrup.
Test Example ( 1 ) Inhibitory effect of sneezing on antigen stimulation (1) Test substance The test substance was used as a suspension in 0.5% tragacanth solution on the test day. The test solution dose was 2.0 mL per kg body weight, and the same amount of 0.5% tragacanth solution was administered to the control group.
(2) Test animals
Hartley male guinea pig 5 weeks old (purchased from Japan SLC) was given a solid feed and tap water in an environmentally controlled breeding device (manufactured by CLEA Japan) at a temperature of 20-26 ° C and a humidity of 35-65%, and lighting time It was used after pre-breeding under the condition of 7:00 to 19:00.
(3) Test method (1) Preparation of active sensitized guinea pig 0.5 ml of antigen solution (ovalbumin 50 mg / mL: manufactured by Sigma Chemical Co., Ltd.) is administered to the back and abdominal cavity of 6-week-old guinea pigs for immunization. One week later, the same amount of antigen is administered in the same manner and boosted. Seven to nine days after the booster, fast about 24 hours and serve as an active sensitized guinea pig.
(2) Induction of sneezing induced by antigens After checking and checking the health condition of the animals, the animals are distributed so that the weights of five animals per group are averaged. Next, 0.1 mL of the antigen solution (50 mg / mL) is dropped into each nasal cavity of the guinea pig. Thereafter, the symptom is observed for 15 minutes, and the number of sneezing is counted to obtain the intensity of the antigen-induced nasal symptom.
(3) Inhibitory action of test substance The test substance is administered using an oral sonde one hour before the antigen nasal drop in (2) above. The sneezing suppression rate (%) is calculated from the following formula.
[0028]
Inhibition rate (%) = [1-average number of sneezing in test substance administration group / average number of sneezing in control group] × 100
(4) Test results Table 5 shows the results of the sneezing inhibition rate for each single agent and combination of pseudoephedrine hydrochloride [P (mg / Kg)] and isopropamide iodide [I (mg / Kg)].
[0029]
[Table 5]
The combination of pseudoephedrine hydrochloride and isopropamide iodide showed an excellent sneezing suppression effect.
Table 6 shows the results of the sneezing inhibition rate for each single agent and combination of pseudoephedrine hydrochloride [P (mg / Kg)] and ambroxol hydrochloride [A (mg / Kg)].
[0030]
[Table 6]
The combination of pseudoephedrine hydrochloride and ambroxol hydrochloride showed an excellent sneezing suppression effect.
Table 7 shows the results of the sneezing inhibition rate for each single agent and combination of pseudoephedrine hydrochloride [P (mg / Kg)] and phenylephrine hydrochloride [F (mg / Kg)].
[0031]
[Table 7]
The combination of pseudoephedrine hydrochloride and phenylephrine hydrochloride showed excellent sneezing suppression effect.
[0032]
【The invention's effect】
The medicament containing the pseudoephedrine of the present invention and halogenated isopropamide, ambroxol and / or phenylephrine (especially those used for suppression of rhinitis or sneezing or runny nose) has a remarkable effect and is useful as a medicament. .
Claims (4)
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JP2002364645A JP4695326B2 (en) | 2001-12-21 | 2002-12-17 | Pharmaceutical composition for rhinitis |
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EP1417961A1 (en) * | 2002-11-08 | 2004-05-12 | Boehringer Ingelheim International GmbH | New pharmaceutical compositions containing a combination of ambroxol or bromhexine and isopropamide iodide |
DE10332472A1 (en) * | 2003-07-16 | 2005-02-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Ambroxol for the treatment of tinnitus |
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