JP4318899B2 - Anti-cold medicine - 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
【００２１】
【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
【００２２】
【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
【００２３】
【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 ）カプサイシン暴露吸入に対する咳嗽抑制効果
（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、５乃至９日間の予備飼育後に使用した。
（３）試験方法
▲１▼カプサイシンによる咳嗽の誘発
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。動物を樹脂製の暴露箱（48×48×46cm）内にセットし、超音波ネブライザーでエアゾール化したカプサイシン液（10μg/mL）を５分間暴露吸入させる。この間に誘発する咳嗽回数を計測する。
▲２▼咳嗽抑制作用
被験物質は経口ゾンデを用いて、カプサイシン暴露吸入の１時間前に投与する。抑制率(％)は下式より算出する。
【００２４】
【数１】
抑制率(%)＝[１−被験物質投与群の平均咳嗽回数／対照群の平均咳嗽回数]×100
（４）試験結果
プソイドエフェドリンとヨウ化イソプロパミドの各単剤および組合せによる咳嗽抑制率の結果を表５に示す。
【００２５】
【表５】

塩酸プソイドエフェドリン又はヨウ化イソプロパミド単独では、咳嗽抑制効果を示さなかったが、両者を組み合わせることにより、優れた咳嗽抑制効果を示した。
【００２６】
【発明の効果】
本発明の、プソイドエフェドリンとヨウ化イソプロパミドを有効成分とする抗感冒剤は、それぞれ単独では予想し得なかった鎮咳効果が発現するので、例えば鎮咳剤又は抗鼻炎剤として有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an anti-cold drug containing pseudoephedrine and iodopropamide as active ingredients.
[0002]
[Prior art]
Drugs that can be purchased by general consumers without requiring a doctor's prescription are called over-the-counter drugs. Many over-the-counter drugs are complex agents containing a plurality of active ingredients. Depending on the product, it is not uncommon to have more than 10 kinds of ingredients. For example, cold medicines contain antipyretic analgesics, antihistamines, antitussives, sympathomimetic drugs, expectorants, central nervous system stimulants, and other active ingredients. However, the frequency of unexpected drug interactions is expected to increase rapidly as the number of active ingredients increases, and the potential risk when used in combination with drugs for other diseases cannot be ignored.
[0003]
It would be ideal if the number of ingredients can be reduced without reducing the effectiveness. However, for example, diseases such as the common cold have various symptoms, and it is extremely difficult to realize a reduction in the number of ingredients without reducing the effectiveness for each symptom. In addition, it is difficult to predict specifically which combination of drugs can be achieved, and it can be said that there is no method other than testing and searching each of a huge number of combinations.
[0004]
So far, conventional techniques that have developed the antitussive effect by combining ingredients other than the antitussive agent and have the possibility of omitting the antitussive agent include, for example, ketotifen, an antihistamine agent, ambroxol, an antiphlogistic agent, and an anti-inflammatory enzyme agent. A combination of a certain lysozyme and an antitussive effect (JP-A-10-45591), an antihistamine chlorpheniramine, carbinoxamine or clemastine, and an expectorant ambroxol (APO) -316568), an antipyretic analgesic that combines an antipyretic analgesic agent with acetaminophen and an antihistamine / antiallergic agent ketotifen or epinastine and caffeine (JP-A-10-17473), an antipyretic analgesic Naproxen, diclofenac, ke Prophine or isopropylantipyrine and expectorant bromhexine or ambroxol combined to develop antitussive effect (JP 2000-80034), antipyretic analgesic agent loxoprofen and expectorant bromhexine or ambroxol formulated antitussive Examples thereof include those exhibiting an effect (Japanese Patent Application Laid-Open No. 2001-172175) and those expressing an antitussive effect by combining emedastine, which is an antihistamine, and guaifenesin, bromhexine or ambroxol, which are an expectorant (Japanese Patent Application Laid-Open No. 2001-226264).
[0005]
[Problems to be solved by the invention]
However, there is no report of obtaining antitussive effect by combining pseudoephedrine and a drug having no antitussive effect. On the other hand, in allergic rhinitis such as hay fever, nasal ventilation resistance increases, so the ratio of mouth breathing increases unconsciously, irritation to the upper respiratory tract increases, and sore throat and cough symptoms gradually accompany it. become. According to the “standard medicine for rhinitis” approved by the OTC drug manufacturing [import] approval standard, antitussives fall under the non-standard components (Pharmaceutical manufacturing guidelines, Yakujijiho, 2000). Thus, if an antitussive effect is added to a rhinitis drug that does not normally contain an antitussive component, it is possible to prevent the occurrence of cough symptoms from nasal inflammation, which is extremely useful.
[0006]
The present invention has been made in view of the above situation, and aims to reduce the number of ingredients in an over-the-counter drug without reducing efficacy, avoiding drug interaction risk, simplifying prescription, and thus manufacturing and development costs. The purpose is to reduce this. Furthermore, it aims at realizing a more effective therapeutic agent for allergic rhinitis symptoms such as hay fever.
[0007]
As a result of intensive studies to overcome the above problems, the present inventors have found that a composition containing pseudoephedrine and isopropamide iodide, both of which do not exhibit an antitussive effect alone, exhibits an antitussive effect. Was completed.
[0008]
[Means for Solving the Problems]
The present invention is an anti-cold agent containing pseudoephedrine and iodopropamide as active ingredients.
[0009]
The present invention also provides an antitussive agent comprising pseudoephedrine and iodopropamide as active ingredients.
[0010]
Furthermore, the present invention is an anti-rhinitis agent comprising pseudoephedrine and iodopropamide as active ingredients.
[0011]
Pseudoephedrine is a pseudoephedrine salt such as pseudoephedrine or pseudoephedrine hydrochloride or pseudoephedrine sulfate.
[0012]
DETAILED DESCRIPTION OF THE INVENTION
Pseudoephedrine and iodopropamide are listed in USP (United States Pharmacopeia) XXIV.
[0013]
The weight% of pseudoephedrine contained when the anti-cold drug of the present invention is a solid preparation is usually 0.1 to 50%, preferably 0.5 to 30%, and isopropamide iodide. % By weight is usually 0.005 to 5%, preferably 0.01 to 2%.
[0014]
The content of pseudoephedrine, which is contained when the anti-cold drug of the present invention is a liquid preparation, is usually 0.1 to 100 mg / mL, preferably 1 to 50 mg / mL, and isopropamide iodide. The content is usually 0.05 to 10 mg / mL, preferably 0.1 to 5 mg / mL.
[0015]
Specific dosage forms of the anti-cold 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. An additive and a base material can be used as appropriate, and can be produced according to the usual method described in the Japanese Pharmacopoeia.
[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 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, purified sucrose, etc. are used as excipients, magnesium metasilicate aluminate or magnesium oxide, etc., stabilizers, corn starch, etc. as adsorbents, hydroxypropyl cellulose, 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; and a pH adjuster such as sodium benzoate. Fragrance, etc. can also be added.
[0019]
【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 ) Cough inhibitory effect on capsaicin exposure and inhalation (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 pigs 5 weeks old (purchased from Japan SLC) were used after 5 to 9 days of preliminary breeding.
(3) Test method {circle around (1)} Induction of cough induced by capsaicin After selecting and checking the health of the animals, the animals are divided so that the weights of five animals per group are averaged. The animal is set in a resin exposure box (48 × 48 × 46 cm) and inhaled with capsaicin solution (10 μg / mL) aerosolized with an ultrasonic nebulizer for 5 minutes. The number of coughs induced during this time is measured.
(2) Cough inhibiting action The test substance is administered using an oral sonde 1 hour before inhalation of capsaicin exposure. The inhibition rate (%) is calculated from the following formula.
[0024]
[Expression 1]
Inhibition rate (%) = [1-average cough count of test substance administration group / average cough count of control group] × 100
(4) Test results Table 5 shows the results of cough suppression rate by each single agent and combination of pseudoephedrine and isopropamide iodide.
[0025]
[Table 5]

Pseudoephedrine hydrochloride or isopropamide iodide alone did not show cough suppression effect, but the combination of both showed excellent cough suppression effect.
[0026]
【The invention's effect】
The anti-cold drug containing pseudoephedrine and isopropamide iodide as active ingredients of the present invention exhibits an antitussive effect that could not be predicted by itself, and thus is useful as, for example, an antitussive agent or an antirhinitis agent.

Claims (1)

Antitussive agent consisting only of pseudoephedrine and isopropamide iodide as active ingredients .