JP2004026813A - Medicinal composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a medicinal composition having an excellent suppressing effect on nasal congestion in allergic rhinitis, especially the nasal congestion in delayed onset phase response. <P>SOLUTION: This medicinal composition consists of an extract of magnolia flos or schizonepeta spike with 50-100 % ethanol as an active ingredient, and especially is a nasal congestion symptom-treating agent. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention is a pharmaceutical composition useful for the treatment of type I allergic diseases such as allergic rhinitis, and more particularly, for suppressing nasal congestion due to late-phase reaction.
[0002]
[Prior art]
Allergic rhinitis is a type I allergic disease characterized by three major symptoms: sneezing, runny nose, and nasal congestion (nasal congestion). Immediate phase reaction and elicitation of sneezing, runny nose, and nasal congestion immediately after the antigen is induced by pollen etc. It is known to exhibit a biphasic response with a late onset response that causes nasal congestion 4 to 24 hours later. Conventionally, antiallergic drugs mainly having antihistamine action have been administered to treat allergic rhinitis, but sneezing and runny nose in the immediate phase reaction are strongly suppressed, but nasal congestion symptoms, especially late phase reaction It is said that the effect is weak for nasal congestion symptoms in. It is known that leukotrienes (LTs) and thromboxanes (TX) are involved in the onset of this late-phase reaction. In addition, chemical mediators such as LTs and TX are produced not only by mast cells but also by eosinophils locally infiltrating in a late-phase reaction.
Therefore, development of an antiallergic drug having an eosinophil infiltration-inhibiting effect as a target for suppressing nasal congestion in the late-phase reaction is desired.
[0003]
Heretofore, Shiny and Kaikai have been used as an aqueous extract or a 30% or less dilute ethanol extract in a therapeutic agent for rhinitis. However, it has been found that these extracts have little effect on nasal congestion symptoms in the late-phase reaction.
In addition, the extract of 50% to 100% ethanol extracted from Shiny and Kaigai is not used as a remedy for rhinitis, and its therapeutic effect on nasal congestion symptoms, especially on nasal congestion symptoms in late-phase reaction, is completely known. Absent.
[0004]
[Problems to be solved by the invention]
The present invention provides a therapeutic agent for allergic rhinitis having an excellent effect on suppressing nasal congestion symptoms for allergic rhinitis, particularly an agent for treating allergic rhinitis having an excellent effect on suppressing nasal congestion symptoms in late-onset phase reaction. That is.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to solve such problems, and as a result, 50% to 100%, preferably 70% to 100% of ethanol extract of Shiny and oysters has a strong eosinophil infiltration inhibitory effect and is allergic. The present inventors have found that the present invention has an excellent effect in suppressing nasal congestion symptoms of rhinitis, and particularly has an excellent effect in suppressing nasal congestion symptoms in a late-phase reaction, and completed the present invention.
[0006]
That is, the present invention is a pharmaceutical composition useful for the treatment of nasal congestion, comprising an extract of 50-100%, preferably 70-100% ethanol extract of Shiny or Kaikai as an active ingredient.
[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
In the present invention, the effective amount of 50% to 100%, preferably 70% to 100% ethanol extraction of Shiny and Kayai is 0.01 to 100 g, preferably 0.1 to 100 g per day, as a raw drug equivalent orally. 1 to 10 g is preferred. These crude drugs are actually blended into the preparation in the form of crude drug powder, crude drug extract and the like.
[0008]
The pharmaceutical composition of the present invention is adjusted to a preparation for oral or parenteral administration. Examples of the preparation for oral administration include tablets, pills, capsules, granules, powders, solid preparations such as chewable tablets, syrups, drinks and the like. And manufactured by a conventional method. When preparing a solid preparation, an excipient, a lubricant, a disintegrant, and the like can be used as necessary. In the case of preparing a solution, a surfactant, a solubilizing agent, a buffer and the like can be used as necessary.
In addition, preservatives, flavors, pigments, sweeteners, flavoring agents, fresheners and the like can be used.
[0009]
The preparation for parenteral administration is prepared as a powder or liquid, and is administered to the nasal mucosa by spraying or the like.
[0010]
The pharmaceutical composition of the present invention can be administered once a day or divided into 2 to 6 times a day.
[0011]
【Example】
Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples.
[0012]
Example 1
A mixture of 1500 g of Shiny 70% ethanol extract powder, 150 g of crystalline cellulose, 75 g of sucrose, 31.5 g of mannitol, 300 g of hydroxypropyl cellulose, 450 g of low-substituted hydroxypropyl cellulose, 45 g of light anhydrous silicic acid, 135 g of magnesium aluminate metasilicate, The mixture was granulated with purified water using a stirring granulator, dried using a fluidized bed drier, mixed with 13.5 g of magnesium stearate and mixed using a rotary tableting machine to obtain 300 mg tablets.
[0013]
Example 2
1000 g of Shiny 70% ethanol extract powder, 900 g of crystalline cellulose, 300 g of sucrose, 1110 g of mannitol, 900 g of hydroxypropyl cellulose, 90 g of light anhydrous silicic acid and 155 g of magnesium aluminate metasilicate were mixed, and mixed with a water / granulation dryer. The mixture was granulated with an ethanol mixture (3: 7), dried, and mixed with 45 g of magnesium aluminate metasilicate to obtain 1.5 g of powder per package.
[0014]
Example 3
Shiny 70% ethanol extract powder 1000g, calcium hydrogen phosphate 428g, potato starch 360g, crystalline cellulose 360g, hydroxypropylcellulose 120g, light anhydrous silicic acid 36g, magnesium stearate 24g, magnesium silicate 72g, dry granulation The mixture was granulated by a machine to obtain 400 mg of capsules per capsule.
[0015]
Example 4
1500 g of Kaikai 70% ethanol extract powder, 200 g of crystalline cellulose, 30 g of sucrose, 28 g of mannitol, 240 g of hydroxypropylcellulose, 240 g of low-substituted hydroxypropylcellulose, 30 g of light anhydrous silicic acid, and 120 g of magnesium aluminate metasilicate are mixed and stirred. The mixture was granulated with purified water using a granulator, dried with a fluid bed dryer, 12 g of magnesium stearate was added and mixed, and one tablet of 400 mg was obtained using a rotary tableting machine.
[0016]
Example 5
1500 g of Kaikai 70% ethanol extract powder, 400 g of crystalline cellulose, 300 g of sucrose, 1110 g of mannitol, 900 g of hydroxypropylcellulose, 90 g of light anhydrous silicic acid, and 155 g of magnesium aluminate metasilicate are mixed in a fluidized bed granulating dryer. The mixture was granulated with an ethanol mixture (3: 7), dried, and mixed with 45 g of magnesium aluminate metasilicate to obtain 1.5 g of powder per package.
[0017]
Example 6
1500 g of extract of 70% ethanol extracted from kaigai, 128 g of calcium hydrogen phosphate, 160 g of potato starch, 360 g of microcrystalline cellulose, 120 g of hydroxypropylcellulose, 36 g of light anhydrous silicic acid, 24 g of magnesium stearate and 72 g of magnesium silicate, and dry granulation The mixture was granulated by a machine to obtain 400 mg of capsules per capsule.
[0018]
Test Example: OVA-induced nasal eosinophil infiltration reaction test of mouse Animal BALB / c mice (female, 5 weeks) were subjected to the experiment after pre-breeding for one week.
[0019]
2. Ovalbumin (OVA), potassium / aluminum sulfate, and test drugs were Shinyi water extract, Shiny 30% ethanol extract, Shiny 70% ethanol extract, Kayai water extract, and Kayai 30% ethanol extract. An extract and a kaikai 70% ethanol extract were used.
[0020]
3. Preparation of Antigen Sensitization 3-1 Alum 60.8 mL of a 10% aqueous solution of potassium aluminum sulfate (stock solution) was added to 600 mL of pure water to adjust the pH to 7.0 to prepare an aluminum hydroxide suspension. This suspension was washed three times by centrifugation (2000 rpm, 10 min) using a phosphate buffer solution (PBS). The washed aluminum hydroxide precipitate was made up to a final volume of 200 mL with PBS and resuspended to prepare an Alum solution (5 mg / ml).
[0021]
3-2 Sensitization Sensitization was performed by intraperitoneally administering 200 μL of an OVA-Alum solution (OVA 5 μg / Alum 5 mg / mL) to BALB / c mice. The sensitization was performed four times: the first sensitization (0 day) and the additional sensitization (4, 13, 26 days).
[0022]
4. Induction of antigen, preparation and administration method of test drug, and evaluation 4-1 Nasal administration of OVA (25 μg / ml, 20 μl) was performed four times every other day seven days after the final sensitization. As test drugs, Shinyi water extract 500mg / kg, Shiny 30% ethanol extract 500mg / kg, Shiny 70% ethanol extract 100mg / kg, 500mg / kg, Kaimai water extract 500mg / kg, Kayai 30% ethanol extract 500 mg / kg, 100% oyster 70% ethanol extract, 500 mg / kg, and 0.5% CMC solution were used as controls. The test drug was dissolved or suspended in a 0.5% carboxymethylcellulose solution, and was orally administered once a day from the day before the first induction to the last day of the induction for 8 consecutive days. In addition, the administration on the day of nasal drop induction was performed one hour before the induction. Six hours after the final induction, the nasal tissues were collected, fixed with formalin, and stained with Luna according to a standard method. Each value represents the number of eosinophils per nasal tissue Level 2 pathological section by mean ± se. The test of the difference between the mean values of the multiple groups was performed using Dunnett's multiple comparison test. The results are shown in FIGS.
[0023]
5. Results 100% / 500mg / kg of the 70% ethanol extract of Shiny and Kaikai significantly suppressed the eosinophil infiltration reaction in the nasal cavity with respect to control. However, 500 mg / kg of the water extract and 30 mg / kg of the extract of Shiny and Kaigai did not significantly inhibit this reaction.
[0024]
Therefore, a crude drug of a 70% ethanol extract of Shiny and mussels has a strong inhibitory action on eosinophil infiltration in the nasal cavity, and a pharmaceutical composition containing a 70% ethanol extract of Shiny and mussels as an active ingredient has chronic inflammation. It has been shown to be effective in the treatment of hyperplastic and rhinitis conditions, especially nasal congestion.
[0025]
【The invention's effect】
The pharmaceutical composition of the present invention has an excellent effect on suppressing nasal congestion due to allergic rhinitis, particularly a nasal congestion symptom in a late-phase reaction, and is useful as a therapeutic agent for nasal congestion symptoms.
[Brief description of the drawings]
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a drawing showing the inhibitory effect of Shinyi's water and 30-70% ethanol extract on nasal eosinophil infiltration.
FIG. 2 is a drawing showing the inhibitory action of eosinophil infiltration reaction in the nasal cavity by the extract of water and 30-70% ethanol extract of scallop.
FIG. 3 is a graph showing the inhibitory effect of a 70% ethanol extract of Shini and Kaigai on eosinophil infiltration in the nasal cavity.

Claims (4)

A pharmaceutical composition comprising, as an active ingredient, a 50-100% ethanol extract of Shiny or Kaikai. A remedy for nasal congestion, comprising a 50-100% ethanol extract of Shiny or Kaikai as an active ingredient. A pharmaceutical composition comprising, as an active ingredient, a 70-100% ethanol extract of Shiny or Kaikai. An agent for treating nasal congestion, comprising a 70-100% ethanol extract of Shiny or Kaikai as an active ingredient.

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