JP2002370977A - Composition for topical application - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for topical application having an excellent feeling of use for an unpleasant sensation including an irritant feeling of a topical application agent comprising ipratropium bromide, flutropium bromide and salts thereof formulated therein. SOLUTION: This composition for the topical application is characterized by formulating one or more kinds selected from the ipratropium bromide, flutropium bromide and salts thereof having the unpleasant feeling of use during topical application with a volatile essential oil ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to the use of topically applied ipratropium bromide, flutropium bromide and their salts, which are used as a parasympathetic blocker, for the discomfort including the irritating sensation or the unpleasant sensation. The present invention relates to providing a topical composition having an excellent feeling. Specifically, one or more volatile essential oils of menthol, camphor, peppermint oil, eucalyptus oil, and peppermint oil are added to one or more selected from ipratropium bromide, flutropium bromide and salts thereof. Combined ingredients,
This is a topical composition having a significantly improved feeling in use.

[0002]

2. Description of the Related Art Both rhinitis and pharyngitis are inflammatory diseases, and their causes are diverse, such as those caused by bacterial infection, those caused by virus, those caused by allergy, and those caused by traumatic injury. In these inflammatory diseases, hypersecretion of local mucosa and airway constriction due to parasympathetic nerve stimulation occur. Symptomatic treatment to reduce and eliminate this symptom early,
This is an important factor in the field of over-the-counter drugs. Currently, parasympathetic blockers and the like are currently used as such symptomatic treatments. However, at the time of these inflammatory diseases, the local mucosa is damaged, and it is easy to receive an unpleasant sensation such as a stimulus. Also, parasympathetic blockers exhibit unpleasant sensations such as irritations due to their scientific composition, which is an obstacle to maintaining and improving compliance.

[0003] Volatile essential oil components such as menthol, camphor, mint oil, eucalyptus oil, and peppermint oil are widely used widely in general foods and quasi-drugs. However, the mechanism related to nerve transmission represented by feeling of use has not been elucidated at present.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a composition for topical application in which the use feeling of ipratropium bromide, flutropium bromide and salts thereof having an unpleasant feeling such as irritation is improved. .

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, menthol,
Volatile essential oil components such as camphor, peppermint oil, eucalyptus oil and peppermint oil inhibit or significantly reduce the transmission of unpleasant sensations of ipratropium bromide, flutropium bromide and their salts, and significantly improve the use of various drugs And completed the present invention based on the findings. That is, the present invention is a composition for topical application characterized by combining ipratropium bromide, flutropium bromide and salts thereof and a volatile essential oil component, which have an unpleasant use feeling when applied topically. The present inventors have achieved, as a candidate substance for improving the feeling of irritation, a drug intended to protect a mucous membrane damaged by an inflammatory disease, such as chondroitin used as an ophthalmic material, in order to achieve the above object. The formulation of sodium sulfate, aluminum hydroxide gel used as a gastric mucosa protective agent, magnesium metasilicate aluminate, etc. was also studied. However, as a material applied to the upper respiratory tract, sufficient action cannot be obtained by simultaneous administration to cover the mucous membrane from the mechanism of action and exert its effect, and it is superior to volatile essential oil components from the viewpoint of improving usability It was speculated that no effect could be obtained. Examples of the salt according to the present invention include hydrochloride, sulfate, nitrate, hydrobromide and the like. Volatile essential oil components are menthol, camphor, peppermint oil, eucalyptus oil and peppermint oil, with menthol being preferred. The topical composition of the present invention may contain, as necessary, an antiallergic drug, an antihistamine, an anti-inflammatory enzyme, a bronchodilator, a sympathomimetic, an anticholinergic, a vitamin, and a bactericidal disinfectant. Components such as a drug, an astringent, a local anesthetic, a crude drug, and a fragrance can be appropriately blended. These components can be used alone or as a mixture with one another.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The topical composition of the present invention is a composition used in a wide range of medicines, quasi-drugs, miscellaneous goods and the like applied to the upper respiratory tract, and is more preferably a nasal spray form or inhalation It can be used as a spray form. Surfactants, solubilizing agents, buffers, preservatives, osmotic pressure adjusting agents, and the like can be used as necessary as additives for adjusting the preparation. In addition, preservatives, fragrances, coloring agents, and the like can be used. The topical composition of the present invention can be produced by a conventional method such as mixing, dissolving, and filling, depending on the form of the preparation. The preparation can be produced according to each section of the Japanese Pharmacopoeia General Rules for Preparations.

[0007] In the present invention, when ipratropium or a salt thereof is used, the dose is 30 to 30 per day for an adult.
It is 200 μg, preferably 60 to 160 μg. This is 0.0075 as the concentration for the whole preparation.
-0.05% by weight, preferably 0.015-0.0%.
4% by weight. When flutropium or a salt thereof is used, the amount is 45 to 280 μg, preferably 90 to 240 μg per adult day. This is 0.01125 to 0.07% by weight based on the whole preparation,
Preferably it is 0.0225 to 0.06% by weight. Also,
The volatile essential oil components menthol, camphor, peppermint oil, eucalyptus oil and peppermint oil are each 0.001 to 1.0% by weight, preferably 0.005 to 0.5% by weight based on the whole preparation. is there.

[0008] The combination of ipratropium bromide, flutropium bromide and salts thereof and a volatile essential oil component is such that the volatile essential oil component is 0.014 to 1 part by weight of the parasympathetic blocker.
133 parts by weight, preferably 0.833 to 66.7 parts by weight. The compounding concentration can be appropriately increased or decreased depending on the use subject such as age, weight, and medical condition. The topical composition of the present invention is generally administered to an adult by dropping or spraying an appropriate amount once or several times into the nostrils and oral cavity at one time.

[0009]

As described above, ipratropium bromide, flutropium bromide and salts thereof and menthol are used as constituents.
By blending with one or more selected from the group consisting of camphor, peppermint oil, eucalyptus oil and peppermint oil, it inhibits unpleasant sensations such as irritation caused when using these drugs or A topical composition was obtained which significantly reduced or eliminated.

[0010]

The present invention will be further described with reference to the following examples and test examples, but the present invention is not limited to the following examples. (Example 1) Of the following components, except for sodium chloride and benzalkonium chloride, were weighed and uniformly mixed, and then purified together with a phosphate (100 mg) buffer solution and 100 mg of benzalkonium chloride (preservative). Dissolved in 80 ml of water, and further 9000 mg of sodium chloride (isotonizing agent)
After adjusting the pH to 7.0 by adding an appropriate amount of sodium hydroxide, purified water was added and dissolved to make the total volume 1 L. The solution was divided into containers of 30 ml each to prepare nasal drops. Ipratropium bromide 100mg l-menthol 5000mg benzalkonium chloride 100mg sodium chloride 9000mg polyoxyethylene hydrogenated castor oil 200mg

(Example 2) Of the following components, except for sodium chloride, were weighed, mixed uniformly, dissolved in 80 ml of purified water together with a phosphate (100 mg) buffer solution, and further dissolved in the following amount of sodium chloride. (Isotonicity agent), after adjusting the pH to 6.8 by adding an appropriate amount of sodium hydroxide,
Purified water was added and dissolved to make the total volume 1 L. The dissolving solution was divided into 15 ml containers to prepare nasal drops. Ipratropium bromide 200 mg Mint oil 100 mg Sodium chloride 9000 mg Methyl parahydroxybenzoate 5000 mg

(Example 3) Of the following components, except for glycerin and benzalkonium chloride, were weighed and uniformly mixed. Then, 20 g of glycerin was combined, and 100 ml of purified water together with 100 mg of benzalkonium chloride (preservative). , And mixed again uniformly, and then purified water was added to dissolve the solution to a total volume of 1 L. The solution was divided into containers of 20 ml each to prepare a stream drug. Ipratropium bromide 100mg eucalyptus oil 100mg dipotassium glycyrrhizinate 1500mg propylene glycol 500mg benzalkonium chloride 100mg

(Example 4) The solution was dissolved in purified water as in Example 3, and the total amount was adjusted to 1 L. The solution was divided into containers of 100 ml each to prepare a nasal spray. Flutropium bromide 250mg dl-Camphor 5000mg dl-Chlorpheniramine maleate 250mg Tetrahydrozoline hydrochloride 100mg Propylene glycol 25000mg Glycerin 25000mg Benzethonium chloride 100mg Polyoxyethylene hydrogenated castor oil 2000mg Saccharin sodium 500mg

(Test Example) Investigation on improvement of feeling of use The composition of Example 1 and a composition containing l-menthol of various concentrations as a comparative composition were prepared, and a nasal spray having a spray amount per application of about 50 μL was prepared. Prepared in a spray container. Use feeling Nasal spray was used for 10 adult panelists (5 males and 5 females), and the score for each composition was evaluated on a scale of 10 points per person (total of 100 points). The total score of the evaluation was determined as the total score of usability evaluation. Point distribution: 10 points: no problem in usability, 7 points:
5 points: slight irritation, etc., but no major problem in usability. 2 points: uncomfortable, poor usability. 0 points: poor usability, unacceptable. In this range, an intermediate score (an integer of 0 to 10) was arbitrarily assigned and evaluated. The results are shown in FIG. As a result, the composition containing l-menthol in an amount of 0.05 to 0.5% by weight had a high score, and the feeling in use was improved.

[0015]

[Brief description of the drawings]

FIG. 1 is a graph showing the degree of improvement in the usability of a test example. The vertical axis indicates the usability evaluation total score. The horizontal axis shows l-menthol concentration (%) in the preparation.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 3/02 101 A61P 3/02 101 11/08 11/08 17/00 17/00 23/02 23 / 02 25/02 104 25/02 104 29/00 29/00 31/04 31/04 37/08 37/08 (72) Inventor Okuhira Ichiro 3-24-1, Takada, Toshima-ku, Tokyo Taisho Seiyaku Co., Ltd. (72) Inventor Joji Nakagami 3-24-1, Takada, Toshima-ku, Tokyo Inside Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3- 24-1, Takada, Toshima-ku, Tokyo Taisho Seiyaku Co., Ltd. F term (reference) 4C076 AA24 AA93 BB21 BB25 CC01 CC04 CC15 CC19 CC22 CC31 DD37T EE53T 4C086 AA01 AA02 CB15 MA01 MA04 MA13 MA56 MA59 NA14 ZA03 ZA27 ZA61 ZB11 ZB13 ZB35 ZC22 4C206 FA33 MA01 MA04 ZC22

Claims (4)

[Claims] 1. A topical composition comprising a volatile essential oil component and one or more selected from ipratropium bromide, flutropium bromide and salts thereof. 2. The topical composition according to claim 1, wherein the volatile essential oil component is one or more selected from the group consisting of menthol, camphor, peppermint oil, eucalyptus oil and peppermint oil. 3. The topical composition according to claim 1, wherein the dosage form is a nasal spray. 4. The topical composition according to claim 1, which is in the form of a spray for inhalation.