JP2748199B2 - Patch for prevention and treatment of bronchial asthma attacks - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch used for preventing and treating bronchial asthma attacks.

[0002]

2. Description of the Related Art Respiratory drugs include bronchodilators and therapeutic agents for bronchial asthma. Bronchodilators are mainly xanthine derivatives and have the effect of expanding the inside of the bronchi,
As an indication, it is used to relieve attacks such as bronchial asthma and bronchitis and reduce symptoms such as dyspnea. The brand names (trademarks) of currently marketed drugs include aminophylline / cholinetheophylline / diprofylline / proxyphylline. However, if you take too much caffeine-containing drinks such as coffee, black tea, and green tea, headache and insomnia will occur. It is generally known that there are side effects such as excitement, anxiety, dizziness, tinnitus, palpitations, tachycardia, nausea, anorexia, etc. It is also known that side effects occur when used in combination with other drugs (xanthine-based preparations / central nervous system stimulants).
Therefore, people with other illnesses must carefully consult their doctor and follow their instructions. Of particular importance is that the use of this drug causes a major obstacle to the normal daily life of drinking coffee and green tea. Next, as a bronchodilator, a sympathetic nerve stimulant is also generally used. This drug has the same indication as the above-mentioned xanthine derivative, but has side effects such as palpitations, increased blood pressure, and headache. -Insomnia, dizziness, sweating, difficulty urinating, etc. ... Many problems, and when used in combination with other drugs, there are many problems such as side effects of arrhythmia and cardiac arrest. The above bronchodilators are administered orally or by inhalation, and all are agents that act directly on the affected site (inhalation) or on the joints (effect on the affected area via blood by oral administration). . Next, there are anti-allergic agents for preventing or suppressing allergic phenomena by antihistamine action as therapeutic agents for bronchial asthma, and these are used for prevention and treatment of bronchial asthma. Various drugs are commercially available even as anti-allergic drugs, and the administration method is exactly the same as that of the above-mentioned bronchodilators by oral administration, inhalation administration and the like. In addition, side effects often occur, such as nausea, anorexia, stomach pain, liver damage, and sleep. Attention must also be paid especially to the combined use with other agents.

[0003] As a special treatment, a skin containing denatured protein (composed of a specially treated Kamen Samaru, a skin extract, a killed bacterium, a filamentous fungus extract and 20% peptone) as a main component is used. Pharmaceutical treatment aimed at causing an internal injection to cause persistent and safe redness and swelling at the injection site, and to reduce or eliminate allergic symptoms by irritating the skin has been attempted. However, this treatment has not been adopted as a general treatment. Next, for the development of allergic diseases,
It is known that not only invasion of an allergen serving as an antigen but also parasympathetic nervous system localization at the onset site plays an important role. With respect to this pathological treatment, the following treatments have been partially implemented at the research stage. That is, it is necessary to first take a small amount (0.1 ml) of the injection solution and intradermally inject it into the upper arm to check for the presence of a shock and the degree of redness and swelling. Intradermal injection of an appropriate amount of up to 0.5 ml, depending on the degree of the above, about 3 days after the first (redness and swelling disappear),
This requires a cumbersome procedure of injecting an appropriate amount of 0.5 ml from the beginning into the skin. In addition, the interval is postponed or shortened depending on the degree of swelling, discontinued when the symptoms disappear, the usage and dosage are complicated, there are individual differences, and there are drawbacks such as severe pain at the time of intradermal injection. , And also need to be under the supervision of a doctor,
At present, this method has not been adopted because there is a limit in the treatment method.

[0004]

As described above, a bronchodilator and a therapeutic agent for bronchial asthma are administered by inhalation or oral administration, which are administered directly or jointly to the site of onset to prevent or treat. However, in the case of the components and administration method of such a drug, especially in the case of continuous use, as described above, in the worst case, there are side effects such as life-threatening, and in the daily life, there are also inconveniences in consideration of the side effects. There is a drawback of being forced, and there is also a major problem of a heavy physical burden. Accordingly, the present invention has been made in view of the above-mentioned problems and the attacks of bronchitis and bronchial asthma, in view of the medical community's research that hypertonia of the parasympathetic nerve at the onset local site plays an important role. Without direct or indirect administration (inhalation / oral administration / injection administration) to the nervous system, the drug is administered percutaneously via the nervous system, and is caused by conventional drug administration to the affected area It is an object of the present invention to provide a patch which eliminates all the above-mentioned side effects and is effective in preventing and treating asthma attacks.

[0005]

The present invention is a water-containing plaster mainly composed of a water-soluble polymer such as gelatin, sodium polyacrylate and sodium carboxymethylcellulose, or natural rubber, synthetic rubber, acrylic resin, vinyl resin or the like. Non-aqueous plaster mainly composed of a base resin or a silicone resin or a blend plaster of both, in which vanillyl amide nonylate, capsaicin, pepper extract, 1-menthol, d1-menthol, peppermint oil, d-camphor, d1
-Percutaneously administered by applying a patch containing 0.01 to 15 w / w% of a skin irritant of camphor, methyl salicylate and a redness medicine to Ryodoraku, and using the skin irritant of the agent, By stimulating the affixed site and stimulating the parasympathetic nervousness at the onset of asthma attack to the parasympathetic nerve at the skin affixed site, it is effective in preventing and treating bronchial asthma attacks and solving the above problems. did. The medicament may be in the form of a patch, such as a circle, a square, a rectangle, and a rhombus, and its area can be freely changed from about 1 cm ² . The skin irritation is correlated with the concentration of the stimulant drug and the area to which the drug is applied, and the skin irritation intensity also differs depending on the site of application, ie, the site of Ryodoraku. In consideration of the treatment conditions such as the administration condition, the state of holding the patch, and the site of the good connection to the patch, the present drug is a plastic film or nonwoven fabric of 1.5 cm to 5 cm on one side of a square or 1.5 cm to 5.0 cm in a circular shape. It is optimal to use a patch form in which the plaster is spread and applied to 50 μm to 2 mm.

[0006]

EXAMPLES Example 1 Nonylate Vanillylamide ... 0.05 w / w% Gelatin ... 5 w / w% Sodium carboxymethylcellulose 5 w / w% glycerin 30 w / w% sodium polyacrylate 2 w / w% purified water ... appropriate amount gelatin And sodium carboxymethylcellulose are dissolved in purified water at 60 ° C. while heating. Glycerin in which vanillyl amide nonylate is dispersed is added to this solution, mixed for a certain period of time (about 5 minutes) under heating, and sodium polyacrylate is added, followed by kneading under the same conditions for 10 minutes. After that, the paste is spread and applied to the non-woven fabric with a constant thickness (400 μm), the polypropylene film is covered on the paste surface, and after cooling, cut into a fixed area or punched using a punch with a fixed diameter. I do.

Example 2 Styrene-isoprene-styrene block copolymer 40
Parts, 35 parts of rosin-modified resin and 25 parts of liquid paraffin are kneaded at a high temperature, 0.15 parts of capsaicin is added, and the mixture is kneaded under the same conditions for a certain period of time to give a polyester film having a thickness of 100 μm. And spread the polypropylene film over the surface of the plaster, cut into a certain area,
Alternatively, it is manufactured by punching using a punch having a constant diameter.

[0008]

The effects of the present invention will be described with reference to the following clinical examples. Clinical Example 1 5-Year-Old Girl: Bronchial Asthma A patient with bronchial asthma is a mild case with wheezing as the chief complaint, but suffers asthma attacks three to five times a year. A sample prepared according to Example 1 (diameter 3.5
was stuck at a rate of once a day in the inner forearm (Ryodoraku H _{1 7)} in accordance cm of a circular patch) in clinical Example 1, wheezing disappeared three weeks after the administration. The “sustained effect” and the “effect at the time of application” of this drug in this case are shown in Table 1 and FIG. 3, respectively. There were no side effects.

[Table 1]

Clinical Example 2 10-year-old girl: Chronic obstructive bronchitis A sample (3.5 cm diameter circular patch) prepared according to Example 2 was used for a patient who had wheezing and airway resistance for 5 years. Anterior chest (Ryodoraku V
M3) showed wheezing and improvement in airway resistance at 3 weeks. As a result of continued application, wheezing and airway resistance were completely eliminated even after 5 months, except for the appearance of wheezing (only twice) due to the common cold. The “sustained effect” and the “effect at the time of application” of this drug in this case are shown in Table 2 and FIG. 4, respectively. In addition,
There were no side effects when applied for a prolonged period of time.

[Table 2]

Investigation of the site of application The present invention has been carefully studied for the most effective skin irritating drug concentration of this agent, the drug area and the application site (Ryodoraku site). Capsaicin is 0.001 to 0.25, preferably 0.05 to
0.1 w / w%, more preferably 0.01 to 0.05 w
/ W%, pepper extract is 0.01-1.0 w / w
%, Preferably 0.05 to 0.5 w / w%, preferably 0.1 to 0.3 w / w%, 1-menthol, d1-menthol, d-camphor, d1-camphor and methyl salicylate are 0.01% ~ 20.0 w / w%, preferably 0.1
-10 w / w%, more preferably 1-5 w / w%. The drug area ^{1cm 2 ~400cm} 2, preferably ^{3 cm} 2 100 cm ^2, more preferably ^{5 cm} 2 to 2
5 cm ² . Ryodoraku sites are the chest and limbs,
The Ryodoraku sites shown in FIG. 1 are more preferably the respective portions in the Ryodoraku diagram shown in FIG. 2, and among them, H ₁ 12
(Nakafu), H 1 _{7 (Sawada} Nagareana outermost) has learned that it is optimal.

[0011]

[Brief description of the drawings]

FIG. 1 is a Ryodoraku explanatory diagram showing a drug application site.

FIG. 2 is a detailed view of Ryodoraku showing details of a drug application site.

FIG. 3 is an effect diagram at the time of application in Clinical Example 1.

4 is an effect diagram at the time of application in Clinical Example 2. FIG.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 35/78 A61K 35/78 Q ADA ADAR

Claims (1)

(57) [Claims] 1. A plaster body containing nonylate varnishylamide, capsaicin, capsicum extract, d1 menthol, 1-menthol, peppermint oil, d-camphor, d1-camphor,
0.01 mg of skin-irritating drug of methyl salicylate
A patch for the prevention and treatment of bronchial asthma, which is percutaneously administered by being applied to Ryodoraku, characterized by containing -15% w / w.