JP2003146871A - Antirheumic agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an excellent antirheumic agent. SOLUTION: The antirheumic agent contains pseudoephedrine and isopropamide iodide as active ingredients.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an anti-cold agent containing pseudoephedrine and isopropamide iodide as active ingredients.

[0002]

2. Description of the Related Art A drug that can be purchased by a general consumer without requiring a prescription from a doctor is called an over-the-counter drug. Most over-the-counter drugs are complex agents containing a plurality of active ingredients, and it is not uncommon for some products to contain more than 10 types of ingredients. For example, anti-pyretic analgesics, antihistamines, antitussives, sympathomimetics, expectorants, central nervous system stimulants, and other active ingredients are mixed in cold remedies. However, as the number of active ingredients increases, the frequency of unexpected drug interactions is expected to increase rapidly, and in particular,
The potential risks of co-administration with drugs for other diseases cannot be ignored.

It would be ideal if the number of components to be blended could be reduced without reducing the effectiveness. However, for example, in diseases such as common cold, there are various symptoms, and it is extremely difficult to reduce the number of blended components without reducing the effectiveness for each symptom. In addition, it is difficult to predict specifically which combination of drugs will make it possible, and it can be said that there is no other way than to test and search from among a huge number of combinations.

[0004] Heretofore, examples of conventional techniques that have brought about the possibility of omitting the antitussive agent by expressing the antitussive effect by mixing components other than the antitussive agent include, for example, ketotifen which is an antihistamine, ambroxol which is an expectorant, and antiphlogistic. A compound having an antitussive effect by adding lysozyme which is an enzyme agent (Japanese Patent Laid-Open No. 10-45591), an antihistaminic agent such as chlorpheniramine, carbinoxamine or clemastine and an expectorant agent ambroxol which exerts an antitussive effect ( JP-A-10-31656
8), which has an antitussive effect by combining acetaminophen, which is an antipyretic analgesic, and ketotifen or epinastine and caffeine, which are antihistamine / antiallergic agents (JP-A-10-17473), and naproxen, which is an antipyretic analgesic. , Diclofenac, ketoprofen or isopropylantipyrine and an expectorant bromhexine or ambroxol to produce an antitussive effect (JP 2000-80034), antipyretic analgesic loxoprofen and expectorant bromhexine or ambroxol. A compound which exhibits an antitussive effect by blending (Japanese Patent Laid-Open No. 2001-172175), an antihistamine agent such as emedastine and an expectorant agent which exhibits an antitussive effect by combining guaifenesin, bromhexine or ambroxol JP 2001-226264) and the like.

[0005]

However, there is no report that a pseudotussive effect was obtained by mixing pseudoephedrine and a drug having no antitussive effect. On the other hand, in allergic rhinitis such as hay fever, the ratio of mouth breathing increases unconsciously due to increased nasal airway resistance, which increases irritation to the upper respiratory tract and gradually accompanies sore throat and coughing symptoms. become. According to the “Oral drug for rhinitis” approval of over-the-counter drug manufacturing [import], antitussives fall under non-standard ingredients (Pharmaceutical manufacturing guidelines, Yakuji Jikhosha, 2000). Therefore, usually, if an antitussive effect is added to a drug for rhinitis that does not contain an antitussive component, it is possible to prevent complications of cough symptoms from symptoms of nasal inflammation, which is extremely useful.

The present invention has been made in view of the above circumstances, and aims to reduce the number of components to be incorporated in over-the-counter drugs without reducing the efficacy, avoiding the risk of drug interaction, simplifying the formulation, and eventually producing the drug. Also, it aims to reduce development costs. Still another object is to realize a more effective therapeutic drug for allergic rhinitis symptoms such as pollinosis.

As a result of intensive studies to overcome the above-mentioned problems, the present inventors have found that a composition containing pseudoephedrine and isopropamide iodide, which do not show antitussive effect alone, exhibits antitussive effect. The present invention has been completed.

[0008]

The present invention is an anti-cold agent containing pseudoephedrine and isopropamide iodide as active ingredients.

The present invention is also a cough suppressant containing pseudoephedrine and isopropamide iodide as active ingredients.

Furthermore, the present invention is an anti-rhinitis drug containing pseudoephedrine and isopropamide iodide as active ingredients.

Pseudoephedrine means pseudoephedrine or a salt of pseudoephedrine such as pseudoephedrine hydrochloride or pseudoephedrine sulfate.

[0012]

DETAILED DESCRIPTION OF THE INVENTION Pseudoephedrine and isopropamide iodide are listed in USP XXIV.

When the anti-cold agent of the present invention is a solid preparation, the weight% of pseudoephedrine is usually
0.1 to 50%, preferably 0.5 to 30%
And the weight percent of isopropamide iodide is usually
0.005 to 5%, preferably 0.01 to 2
%.

The content of pseudoephedrine, which is contained when the anti-cold agent of the present invention is a liquid preparation, is usually 0.
1 to 100 mg / mL, preferably 1 to 50 mg / mL
The content of isopropamide iodide is usually
It is 0.05 to 10 mg / mL, preferably 0.1 to 5 mg / mL.

Specific dosage forms of the anti-cold agent of the present invention include, for example, tablets, fine granules (including powders), capsules,
Examples thereof include liquids (including syrups) and the like, which can be manufactured according to the usual methods described in the Japanese Pharmacopoeia and the like, using additives and base materials suitable for each dosage form as appropriate.

In each of the above dosage forms, various commonly used additives may be used depending on the dosage form.

For example, in the case of tablets, lactose, crystalline cellulose and the like are used as excipients, magnesium aluminometasilicate or magnesium oxide and the like are used as stabilizers, hydroxypropylcellulose and the like are used as coating agents, and magnesium stearate and the like are used as lubricants. It can be used as a bulking agent, and in the case of fine granules and capsules, lactose, purified sucrose, etc. are used as excipients, magnesium aluminometasilicate or magnesium oxide etc. are used as stabilizers, and corn starch etc. are adsorbed. As an agent, hydroxypropyl cellulose or the like can be used as a binder.

In each of the above dosage forms, if necessary, a disintegrating agent such as crospovidone; a surfactant such as polysorbate;
Adsorbents such as calcium silicate; coloring agents such as iron sesquioxide and caramel; pH adjusting agents such as sodium benzoate; perfumes;
Etc. can also be added.

[0019]

EXAMPLES The present invention will be described in more detail below by showing Examples, but the scope of the present invention is not limited to these. (Example 1) Tablet (1) ingredient

[0020]

[Table 1]6 tablets Pseudoephedrine 180mg Isopropamide iodide 7mg Magnesium oxide 400mg Magnesium metasilicate aluminate 144mg Crystalline cellulose 120mg Corn starch 140mg Hydroxypropyl cellulose 60mg Croscarmellose sodium 15mg Magnesium stearate 24mg Triacetin 6mgLactose       Total 1400mg (2) Manufacturing method Take the above ingredients and amounts, and add them to the "Tablets" section of the Japanese Pharmacopoeia General Regulations.
The tablets are manufactured according to the above. (Example 2) Fine granules (1) component

[0021]

[Table 2] Pseudoephedrine in 3 packs 180 mg Isopropamide iodide 7 mg Magnesium oxide 400 mg Magnesium aluminometasilicate 144 mg Purified sucrose 1.4 g Stevia extract product 16 mg Corn starch 1.2 g Polysorbate 80 80 mg Magnesium stearate 24 mg Lactose Suitable total amount 4500 mg (2 ) Manufacturing method Using the above ingredients and amounts, a fine granule is manufactured in accordance with the general regulations of the Japanese Pharmacopoeia, "Granule". Example (3) Capsule (1) component

[0022]

[Table 3] Pseudoephedrine in 6 capsules 180 mg Isopropamide iodide 7 mg Magnesium oxide 400 mg Corn starch 630 mg Polysorbate 80 48 mg Magnesium stearate 24 mg Lactose Appropriate capsules 480 mg Total 2500 mg (2) Preparation method After preparing the fine granules in accordance with the section of “,” the capsules are filled to prepare hard capsules. Example (4) Syrup (1) component

[0023]

TABLE 4 30mL of pseudoephedrine 180mg isopropamide iodide 7mg Sodium benzoate 240mg citrate 60mg sucrose 1.5g concentrated glycerin 1.8g polyvinyl alcohol 120mg hydrochloride qs Sodium hydroxide qs Purified water qs (2) Preparation takes the components and amounts , Japanese Pharmacopoeia "Syrup"
After preparing the syrup according to the item (1), fill a brown glass bottle to prepare the syrup. (Test Example 1) Cough suppressive effect on inhalation exposed to capsaicin
Fruit (1) Test substance The test substance was used as a suspension with 0.5% tragacanth solution on the day of the test. The amount of test substance administered is 2.
The control group was given 0 mL, and the same amount of 0.5% tragacanth solution was administered. (2) Test animal Hartley male guinea pig 5 weeks old (purchased from Japan SLC)
Were used after 5 to 9 days of preliminary breeding. (3) Test method Induction of cough by capsaicin After inspecting the health condition of the animals and selecting, the animals are sorted so that the weights of 5 animals per group are averaged. Exposing animals to resin exposure boxes (48
X 48 x 46 cm) and aerosolize the capsaicin solution (10 μg / mL) with an ultrasonic nebulizer for 5 minutes to inhale. The number of coughs evoked during this period is measured. Cough suppressive effect The test substance is administered using an oral sonde 1 hour before inhalation exposed to capsaicin. The inhibition rate (%) is calculated by the following formula.

[0024]

[Equation 1] Suppression rate (%) = [1-average number of coughs in test substance-administered group / average number of coughs in control group] x 100 (4) Test results Cough inhibition by pseudoephedrine and isopropamide iodide The result of the rate is shown in Table 5.

[0025]

[Table 5] Test substance (mg / Kg) Cough suppression rate (%) Pseudoephedrine hydrochloride (33) -3 Isopropamide iodide (1) 0 Pseudoephedrine hydrochloride (33) + Isopropamide iodide (26) Pseudoephedrine hydrochloride or isopropamide iodide The cough suppressive effect alone was not shown, but the combination of the two showed excellent cough suppressive effect.

[0026]

The anti-cold agent of the present invention containing pseudoephedrine and isopropamide iodide as active ingredients exhibits antitussive effects which cannot be expected by themselves.
For example, it is useful as an antitussive agent or an antirhinitis agent.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yasuhiro Torizumi             3-5-1, Nihonbashihonmachi, Chuo-ku, Tokyo             Sankyo Co., Ltd. F-term (reference) 4C206 AA01 AA02 FA10 GA09 GA22                       MA02 MA04 NA06 ZA34 ZA62                       ZB11 ZB33

Claims (3)

[Claims] 1. An anti-cold agent comprising pseudoephedrine and isopropamide iodide as active ingredients. 2. A cough suppressant comprising pseudoephedrine and isopropamide iodide as active ingredients. 3. An anti-rhinitis drug containing pseudoephedrine and isopropamide iodide as active ingredients.