JP2009197011A - Antirheumic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new antitussive agent that contains pseudoephedrine and iodoisopropamide and does not contain an antitussive ingredient. <P>SOLUTION: The antitussive agent is characterized by containing pseudoephedrine and iodoisopropamide and not containing an antitussive ingredient. The composition containing pseudoephedrine and iodoisopropamide, neither of which has an antitussive effect by itself, has been found to develop the antitussive effect. With the antitussive agent, reduction of the number of components of a general medicine without reducing its effect, avoidance of a drug interaction risk, simplified prescription and reduction of production and development costs are intended. The antitussive agent is further useful for realizing a more effective medicine for a symptom of allergic rhinitis such as pollinosis. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an antitussive agent characterized by containing pseudoephedrine and isopropamide iodide and not containing an antitussive component.

  Drugs that can be purchased by general consumers without requiring a doctor's prescription are called over-the-counter drugs. Most of the 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.

  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.

  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 (for example, see Patent Document 1), an antihistamine chlorpheniramine, carbinoxamine or clemastine and an expectorant ambroxol (for example, an antitussive effect) ), An antipyretic analgesic agent, acetaminophen, and an antihistamine / antiallergic agent ketotifen or epinastine and caffeine are combined to develop an antitussive effect (see, for example, Patent Document 3). , Naproxen and diclofenac, antipyretic analgesics Formulated with ketoprofen or isopropylantipyrine and expectorant bromhexine or ambroxol to develop antitussive effect (see, for example, Patent Document 4), antipyretic analgesic agent loxoprofen and expectorant bromhexine or ambroxol And those that have an antitussive effect (see, for example, Patent Document 5).

JP 10-45591 A JP-A-10-316568 JP 10-17473 A JP2000-80034 JP 2001-172175 A

  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, Yakuho Jishosha, 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.

  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.

  As a result of intensive studies to overcome the above-mentioned problems, the present inventors have found that a composition containing pseudoephedrine and iodopropamide, both of which do not exhibit an antitussive effect alone, exhibits an antitussive effect. Was completed.

  The present invention is an antitussive agent characterized by containing pseudoephedrine and isopropamide iodide and not containing an antitussive component, although it does not contain a commonly known antitussive component.

  Pseudoephedrine refers to a pseudoephedrine salt such as pseudoephedrine or pseudoephedrine hydrochloride or pseudoephedrine sulfate.

  The antitussive agent characterized in that it contains pseudoephedrine and isopropamide iodide and does not contain an antitussive component of the present invention exhibits an antitussive effect that could not be expected by itself. It is useful as a cold medicine and an antirhinitis agent having antitussive action.

  Pseudoephedrine and iodopropamide are listed in USP (United States Pharmacopeia) XXIV.

  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%.

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

  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.

  In the above dosage forms, various commonly used additives can be used depending on the dosage form.

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.

  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.

  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) Component

(Table 1)
6 tablets
Pseudoephedrine 180mg
Isopropamide iodide 7mg
Magnesium oxide 400mg
Magnesium aluminate metasilicate 144mg
Crystalline cellulose 120mg
Cornstarch 140mg
Hydroxypropylcellulose 60mg
Croscarmellose sodium 15mg
Magnesium stearate 24mg
Triacetin 6mg
Lactose appropriate amount
Total 1400mg

(2) Manufacturing method Take the above ingredients and quantities, and manufacture tablets according to the section “General Tablets” “Tablet”.

(Example 2) Fine granule (1) component

(Table 2)
Pseudoephedrine 180mg in 3 packs
Isopropamide iodide 7mg
Magnesium oxide 400mg
Magnesium aluminate metasilicate 144mg
Purified white sugar 1.4g
Stevia extract product 16mg
Corn starch 1.2g
Polysorbate 80 80mg
Magnesium stearate 24mg
Lactose appropriate amount
Total 4500mg

(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) Component

(Table 3)
180mg pseudoephedrine in 6 capsules
Isopropamide iodide 7mg
Magnesium oxide 400mg
Corn starch 630mg
Polysorbate 80 48mg
Magnesium stearate 24mg
Lactose appropriate amount capsule 480mg
Total 2500mg

(2) Manufacturing method Take the above components and the amount, and make a fine granule according to the section of the Japanese Pharmacopoeia General Rules “Granule”, then fill the capsule to make a hard capsule.

Example (4) Syrup (1) Ingredient

(Table 4)
Pseudoephedrine 180mg in 30mL
Isopropamide iodide 7mg
Sodium benzoate 240mg
Citric acid 60mg
Sucrose 1.5g
Concentrated glycerin 1.8g
Polyvinyl alcohol 120mg
Hydrochloric acid appropriate amount sodium hydroxide appropriate amount purified water appropriate amount

(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 inhibiting 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 dose of the test substance was 2.0 mL per kg body weight, and the same amount of 0.5% tragacanth 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 1) Induction of cough by capsaicin After checking and selecting the health condition of animals, the animals are distributed so that the weight of five animals per group is averaged. The animals are set in a resin exposure box (48 × 48 × 46 cm), and capsaicin solution (10 μg / mL) aerosolized with an ultrasonic nebulizer is inhaled by exposure for 5 minutes. The number of coughs induced during this time is measured.
2) Cough suppressive 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.

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 the cough suppression rate by each single agent and combination of pseudoephedrine and isopropamide iodide.

(Table 5)
Test substance (mg / Kg) Cough suppression rate (%)
Pseudoephedrine hydrochloride (33) 3
Isopropamide iodide (1) -3
Pseudoephedrine hydrochloride (33) + Isopropamide iodide (1) 26

Pseudoephedrine hydrochloride or isopropamide iodide alone did not show cough suppression effect, but the combination of both showed excellent cough suppression effect.

  An antitussive agent characterized by containing pseudoephedrine and isopropamide iodide and not containing an antitussive component according to the present invention.

Claims (1)

  An antitussive agent comprising pseudoephedrine and isopropamide iodide and not containing an antitussive component.