JP2003055206A - Medicine composition for nasal cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a medicine composition for the nasal cavity, having ameliorating effects on congestive symptoms of nasal mucosa. SOLUTION: This medicine composition for the nasal cavity is obtained by formulating (a) one or more kinds selected from the group consisting of flunisolide, beclomethasone, fluticasone and their salts with (b) one or more kinds selected from the group consisting of epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and their salts and is used in the form of a nasal drop and nasal ointment.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical composition for the nasal cavity, which has an improved effect of removing or reducing hyperemic symptoms of the mucosa among various symptoms of the nasal mucosa.

[0002]

BACKGROUND OF THE INVENTION Flunisolide, beclomethasone and fluticasone have the purpose of suppressing inflammation of the nasal mucosa, and epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine and methylephedrine have the purpose of suppressing swelling of the nasal mucosa. Each is a widely used drug. Although many drugs have been known so far, compositions combining flunisolide, beclomethasone, fluticasone and epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and salts thereof are not known at present. On the other hand, although many pharmaceutical compositions for nasal cavity have been known so far, none of them are still sufficient for the effect of removing / alleviating hyperemic symptoms of the nasal mucosa, so that neither the user of the drug nor the user still has it. I was not completely satisfied.

[0003]

Problems of hyperemia of the nasal mucosa are considered to be a form of inflammatory lesions. The causes are wide-ranging, and most of them are caused by bacterial infection up to moss, but in recent years, the association with allergies has become the main etiology. Ideally, the causative therapy is considered to be carried out by removing the causative bacteria and allergens, but in reality, it is difficult to carry out this therapy in daily life. Also,
Although desensitization therapy that reduces the sensitivity of the nasal mucosa is also performed, it is currently not widely used because the treatment period is extremely long and frequently involves hospital visits.

Under these circumstances, symptomatic treatment is the main focus. Therefore, how to eliminate or reduce various symptoms of rhinitis as quickly as possible is an important factor for both treatment and daily life. . Symptoms of hyperemia of the nasal mucosa, which is in direct contact with the outside world, is a condition that is often encountered on a daily basis, and it is a therapeutic point to improve it early from the viewpoint of preventing the transition to a serious disease. Furthermore, although this is a very important factor in the field of over-the-counter drugs, it is still difficult to develop a drug that is sufficiently effective. Therefore, an object of the present invention is to provide a pharmaceutical composition for the nasal cavity, which has a high effect of removing or reducing hyperemic symptoms of the nasal mucosa.

[0005]

Means for Solving the Problems As a result of earnest research to solve the above problems, the present inventors have found that flunisolide
By combining beclomethasone and fluticasone with epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine and methylephedrine, it was found that they have an extremely excellent effect on the elimination or alleviation of hyperemic symptoms of the nasal mucosa, and completed the present invention. It was That is, the present invention comprises (a) one or more selected from the group consisting of flunisolide, beclomethasone, fluticasone and salts thereof, and (b) epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and salts thereof. It is a pharmaceutical composition for nasal cavity containing one or more selected from the group consisting of:

The respective salts of flunisolide, beclomethasone and fluticasone used in the present invention mainly include hydrochloride, nitrate, sulfate, acetate, propionate, fumarate and the like. Epinephrine used in the present invention,
Examples of the respective salts of ephedrine, tetrahydrozoline, naphazoline, phenylephrine, and methylephedrine include mainly hydrochlorides, nitrates, sulfates and the like.

Examples of the form of the nasal pharmaceutical composition of the present invention when used include nasal drops and nasal ointments. Note that the above nasal drops include a spray agent sprayed by the pressure of gas,
Inhalable propellants are included.

The amount of each active ingredient blended is 0.0005 to 0.25% by weight for flunisolide, beclomethasone and fluticasone, and 0.001 to 0.2% by weight based on the total amount of the nasal pharmaceutical composition of the present invention. Is preferred. If the amount of these components is less than 0.0005% by weight, the action is not sufficiently exhibited, and if it exceeds 0.25% by weight, irritation or damage to the nasal mucosa may occur. On the other hand, epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and salts thereof are 0.0005 to 1.25% by weight, and
~ 1 wt% is preferred. 0.0% for these ingredients
If it is less than 005% by weight, a sufficient decongestant removal effect cannot be obtained,
If it exceeds 1.25% by weight, resistance to action or reaction resistance may occur.

The amount of epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and salts thereof is usually 0.002 to 2500 parts by weight per 1 part by weight of flunisolide, beclomethasone and fluticasone, respectively. It is preferably 0.005 to 1000 parts by weight. The pharmaceutical composition for nasal cavity of the present invention may contain other components in addition to the above components, if necessary.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition for nasal cavity of the present invention can be prepared by a conventional method. The additives used in the preparation of the formulation include surfactants, solubilizers, buffers, etc.
Furthermore, preservatives, dyes, preservatives and the like can be used. The pharmaceutical composition for nasal cavity of the present invention can be prepared in a solid form, a liquid form, or an ointment form by a conventional method. As an additive used in the preparation of the formulation, in the case of a solid formulation, an excipient such as crystalline cellulose, hydroxypropyl cellulose,
Hydroxypropyl methylcellulose, gelatin, PV
A binder such as P, magnesium stearate, hydrogenated castor oil, a lubricant such as talc, a preservative and the like can be used, and in the case of a liquid preparation, a surfactant, a solubilizing agent, a buffering agent, a preservative and a perfume. , Dyes, preservatives and the like can be used. In the case of an ointment preparation, an ointment base, a surfactant, a solubilizing agent, a buffer, etc., and a preservative, a fragrance, a dye, a preservative and the like can be used. These components can be used alone or in a mixture with each other, and are usually listed in the Japanese Pharmacopoeia General Regulations for Drug Preparation or the over-the-counter drug manufacturing guidelines (2000 version, supervised by Pharmaceutical Affairs Review and Study Group, published by Jiho Co., Ltd.). It is manufactured in accordance with the standards for nasal drops for nasal inflammation. The pharmaceutical composition for nasal cavity of the present invention is usually administered to an adult once or several times by dripping, spraying or applying to both nasal cavities.

[0011]

The present invention will be described in more detail with reference to examples and test examples, but the invention is not limited to these examples. Example 1 The following components and amounts were weighed and uniformly mixed, and then dissolved in 100 mL of purified water to prepare a nasal drop. Flunisolide 20 mg Naphazoline hydrochloride 50 mg Sodium chloride 900 mg Methyl paraoxybenzoate 500 mg

Example 2 The following components and amounts were weighed and uniformly mixed, and then dissolved in 100 mL of purified water to prepare a nasal drop. Fluticasone propionate 40 mg Tetrahydrozoline hydrochloride 100 mg Glycerin 800 mg Polyoxyethylene hydrogenated castor oil 250 mg Methyl paraoxybenzoate 400 mg

Example 3 The following components and amounts were weighed and mixed uniformly, and then dissolved in 100 mL of purified water to prepare a nasal drop. Flunisolide 25 mg dl-methylephedrine hydrochloride 500 mg lidocaine hydrochloride 500 mg sodium chloride 900 mg methyl paraoxybenzoate 250 mg

Example 4 The following components and amounts were weighed and uniformly mixed, and then dissolved in 100 mL of purified water to prepare a nasal drop. Beclomethasone propionate 100 mg Ephedrine hydrochloride 500 mg Lidocaine hydrochloride 500 mg Glycerin 500 mg Sodium chloride 850 mg Methyl paraoxybenzoate 250 mg

Example 5 The following components and amounts were weighed and uniformly mixed, and then dissolved in 100 g of an ointment base (liquid paraffin + polyethylene resin) to prepare a nasal ointment. Beclomethasone propionate 100 mg Phenylephrine hydrochloride 500 mg Propylene glycol 500 mg Methyl paraoxybenzoate 300 mg

(Test Example 1) [Relaxation action of the compounded preparation on rat nasal mucosa hyperemic reaction] <Test method> Six 6-week-old Wister male rats (body weight 200 to 250 g) were used in each group in advance in both nasal cavities. 50 μL of 2.0% capsaicin solution was added to each to induce a hyperemic reaction of the nasal mucosa, and 50 μL of each drug was dropped into both nasal cavities according to the prescription of (Table 1) (the control group was purified to both nasal cavities). 50 μL of water was added dropwise), and 1 hour after the administration, the animals were sacrificed and the nasal cavity was opened, and the decongestant removal effect at that time was visually compared. As an evaluation method, 5 points; very hyperemic, 4 points; fairly hyperemic, 3 points; clearly hyperemic, 2 points; slightly hyperemic, 1 point; Very weak, 0 point; almost no hyperemia was performed in a 6-level evaluation, and the average value among 3 animals was compared.

[0017]

[Table 1]

[Table 1]

<< Test Results >> The results are shown in Table 2 as a grade score of the hyperemic reaction.

[0019]

[Table 2]

As is clear from Table 2, the relieving action on the nasal mucosal hyperemic reaction was remarkably superior to the other control groups in the groups A to B, and the nasal drops of the present invention contained fluticasone propionate, flunisalide and epinephrine. As compared with the case where it was used alone, it had a remarkable effect in reducing and removing the nasal mucosa hyperemia condition.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 11/02 A61P 11/02 43/00 121 43/00 121 (72) Inventor Joji Nakagami Tokyo 3-24-1 Takada, Toshima-ku, Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. F-term (reference) 4C076 AA06 AA12 BB25 CC05 CC10 DD23 DD38 DD44R DD46 FF12 FF14 FF35 4C086 AA01 AA02 BC38 MA02 MA04 MA17 MA28 MA59 NA05 ZA34 4C206 AA01 AA02 FA10 FA14 MA02 MA04 MA37 MA48 MA79 NA05 ZA34

Claims (2)

[Claims] 1. A selected from the group consisting of (a) flunisolide, beclomethasone, fluticasone and salts thereof.
Or 2 or more kinds, and (b) one or more kinds selected from the group consisting of epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine and salts thereof, and a nasal pharmaceutical composition. 2. The pharmaceutical composition for nasal cavity according to claim 1, wherein the form of use is a nasal drop or a nasal ointment.