JP4384435B2 - Sneezing suppression composition - Google Patents

Description

（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
【００２４】
【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
【００２５】
【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
【００２６】
【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。
【００２７】
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又はロキソプロフェンナトリウム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。
【００２８】
【表５】

ロキソプロフェンナトリウムに塩酸プソイドエフェドリンを加えることにより、くしゃみ抑制効果が増強された。
【００２９】
塩酸プソイドエフェドリン又はイブプロフェン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】

イブプロフェンに塩酸プソイドエフェドリンを加えることにより、くしゃみ抑制効果が増強された。
【００３１】
【発明の効果】
本発明のエフェドリン類とフェニルプロピオン酸系解熱消炎鎮痛剤を含有する医薬は、くしゃみ抑制用の医薬（特に、感冒、又は、鼻炎（好ましくは、アレルギー性鼻炎）におけるくしゃみの抑制に用いるもの）として有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a sneezing-suppressing drug containing an ephedrine and a phenylpropionic acid antipyretic anti-inflammatory analgesic.
[0002]
[Prior art]
Sneezing frequently occurs in allergic rhinitis symptoms such as cold and hay fever. Therefore, an antihistamine agent or an antiallergic agent is generally added to the cold medicine or rhinitis medicine to suppress sneezing.
[0003]
However, although antihistamines are fast acting, they have the side effect of causing drowsiness and fatigue. Although second-generation antihistamines that have significantly reduced central nervous system inhibitory effects such as sleepiness have already been used, central nervous system functions such as reduced work efficiency can be suppressed without being aware of sleepiness (this is impaired It is called performance), and it has a great impact on driving and academics. There are quite a few examples in which cognitive functions have declined without noticing, and impaired performance in antihistamines is said to be the most serious and serious side effect for modern people (see, for example, Non-Patent Document 1).
[0004]
Anti-allergic agents have few side effects of antihistamines, but they have a problem that they are not fast-acting and take a long time to develop their efficacy.
[0005]
On the other hand, it is known that phenylpropionic acid antipyretic analgesics are effective in suppressing sneezing (for example, see Non-Patent Document 2 for clinical evaluation of Loxoprofen sodium (CS-600E) for acute upper respiratory tract inflammation). )
[0006]
[Non-Patent Document 1]
Pharmaceutical Affairs Daily, February 22, 2002 [Non-Patent Document 2]
Clinical Medicine Vol.9 No.10 (October) (1993)
[0007]
[Problems to be solved by the invention]
As a result of earnestly examining the suppression of sneezing, the present inventors have found that the addition of ephedrines that do not have a sneezing-inhibiting action by themselves to phenylpropionic acid antipyretic analgesics enhances the sneezing-inhibiting effect, The present invention has been completed.
[0008]
[Means for Solving the Problems]
The present invention
It is a medicine characterized by being used for suppression of sneezing containing ephedrines and phenylpropionic acid antipyretic anti-inflammatory analgesics,
Preferably, a medicament characterized in that it is used to suppress sneezing containing pseudoephedrine and a phenylpropionic acid antipyretic anti-inflammatory analgesic,
More preferably, it is a medicament characterized by being used for suppressing sneezing containing pseudoephedrine and loxoprofen and / or ibuprofen,
Even more preferably, a medicament characterized by being used for suppression of sneezing containing pseudoephedrine and loxoprofen,
It is a medicine characterized by being used for suppression of sneezing containing pseudoephedrine and ibuprofen.
[0009]
Examples of the phenylpropionic antipyretic anti-inflammatory analgesic include drugs having an antipyretic action, anti-inflammatory action and / or analgesic action having a phenylpropionic acid skeleton, such as aluminoprofen, ibuprofen, oxaprozin, zaltoprofen, thiaprofen (acid ), Nabumetone, naproxen, fenoprofen (calcium), pranoprofen, flurbiprofen or loxoprofen (sodium).
[0010]
Examples of ephedrines include pseudoephedrine, ephedrine, and methylephedrine, and preferred examples include pseudoephedrine.
[0011]
Pseudoephedrine refers to pseudoephedrine or a pseudoephedrine salt such as pseudoephedrine hydrochloride or pseudoephedrine sulfate.
[0012]
Loxoprofen is loxoprofen or a salt or hydrate thereof, preferably loxoprofen sodium dihydrate.
[0013]
Ibuprofen is ibuprofen or a pharmacologically acceptable salt thereof.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Pseudoephedrine is listed in USP (United States Pharmacopoeia) XXIV, and ephedrine, methylephedrine, loxoprofen sodium or ibuprofen is listed in Japanese Pharmacopoeia XIV.
[0015]
The weight% of ephedrines contained when the antirhinitis drug of the present invention is a solid preparation is usually 0.01 to 30%, preferably 0.1 to 10%, and phenylpropionic acid. The weight percent of the antipyretic anti-inflammatory analgesic is usually 0.01% to 80%. For example, in the case of loxoprofen, the weight percent is usually 0.01 to 30%, preferably 0.1 to 10%. In the case of ibuprofen, its weight percentage is usually 0.03 to 80%, preferably 0.3 to 40%.
[0016]
The content of ephedrines contained when the antirhinitis drug of the present invention is a liquid is usually 0.1 to 100 mg / mL, preferably 1 to 50 mg / mL. The weight percent of the antipyretic anti-inflammatory analgesic is usually 0.1 to 300 mg / mL, for example, the content of loxoprofen is usually 0.1 to 100 mg / mL, preferably 1 to 50 mg / mL, ibuprofen Is usually 0.3 to 300 mg / mL, preferably 3 to 150 mg / mL.
[0017]
In the present invention, in addition to the above active ingredients, antihistamines or antiallergic drugs, anti-inflammatory drugs, antitussives, expectorants, vitamins and / or herbal medicines, etc., as necessary, are within a range that does not impair the effects of the present invention. Can be blended.
[0018]
Specific dosage forms of the antirhinitis drug of the present invention include, for example, tablets, fine granules (including powders), capsules, liquids (including syrups), and the like. Can be produced according to the usual methods described in the Japanese Pharmacopoeia, using additives and base materials suitable for the above.
[0019]
In the above dosage forms, various commonly used additives can be used depending on the dosage form.
[0020]
For example, in the case of tablets, lactose or crystalline cellulose or the like as an excipient, magnesium metasilicate 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 or purified sucrose is used as an excipient, magnesium aluminate or magnesium oxide as a stabilizer, corn starch or the like as an adsorbent, hydroxypropylcellulose or the like as a binder As can be used.
[0021]
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; and a pH adjuster such as sodium benzoate. Fragrance, etc. can also be added.
[0022]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples and the like, but the scope of 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 against 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) is fed with 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%. 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.
[0027]
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 sneezing inhibition rates for each single agent and combination of pseudoephedrine hydrochloride or loxoprofen sodium.
[0028]
[Table 5]

Addition of pseudoephedrine hydrochloride to loxoprofen sodium enhanced the effect of suppressing sneezing.
[0029]
Table 6 shows the results of sneezing inhibition rates for each single agent and combination of pseudoephedrine hydrochloride or ibuprofen.
[0030]
[Table 6]

By adding pseudoephedrine hydrochloride to ibuprofen, the effect of suppressing sneezing was enhanced.
[0031]
【The invention's effect】
The medicine containing the ephedrine of the present invention and a phenylpropionic antipyretic analgesic is used as a medicine for suppressing sneezing (especially used for suppressing sneezing in colds or rhinitis (preferably allergic rhinitis)). Useful.

Claims (3)

A medicament for suppressing sneezing, comprising pseudoephedrine and loxoprofen or ibuprofen. A medicine for suppressing sneezing containing pseudoephedrine and loxoprofen. A medicine for suppressing sneezing containing pseudoephedrine and ibuprofen.