JP2009235035A - Allergic bronchial asthma inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe medicine which can be administered daily and is capable of significantly inhibiting allergic bronchial asthma. <P>SOLUTION: The allergic bronchial asthma inhibitor contains an extract of loquat seeds. In the allergic bronchial asthma inhibitor, the extract is an alcohol-water extract. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a drug for suppressing allergic bronchial asthma.

  Allergic bronchial asthma is a disease that causes dyspnea due to severe coughing or thinning of the bronchi due to an allergic reaction involving foreign substances such as mites, dust, and air pollutants. Although it is generally said that it is not a fatal disease, in fact, thousands of people die every year due to bronchial asthma and cannot be disregarded.

  In recent years, allergic diseases have become a problem due to various factors such as an increase in allergens such as house dust, a decrease in allergens such as parasites that do not cause bronchial asthma, and an increase in stress. Conventionally, steroids and antihistamines have been used to treat allergic diseases. However, allergic diseases are difficult to cure and require continuous medication, so side effects are likely to occur with these chemical agents. In view of this, a search is being made for natural ingredients that are considered to have relatively few side effects and that have anti-allergic effects.

  For example, Patent Document 1 discloses a functional food in which trehalose is infiltrated into a tissue of a fruit rind, and cocoon is exemplified as a fruit. Moreover, the test result of the antiallergic action of the said functional food is described in the Example.

  By the way, the present inventor has found various effects of cocoon seed extract. For example, a strawberry seed extract suppresses cell fibrosis of the liver and the like (Patent Document 2) and eliminates free radicals (Patent Document 3).

Furthermore, the present inventor has proceeded with research on the strawberry seed extract, and found that the extract suppresses allergic diseases and has applied for a patent (Patent Document 4). The publication describes experimental examples in which the cocoon seed extract is effective against hay fever, allergic rhinitis and allergic conjunctivitis. However, there is no description regarding allergic bronchial asthma.
JP 2001-346537 A JP 2001-240553 A JP 2003-246745 A JP 2008-63255 A

  As described above, search for natural components exhibiting antiallergic action has been conducted so far. However, no natural ingredient has been known that has been demonstrated to have a specific effect on allergic bronchial asthma.

  Therefore, the problem to be solved by the present invention is to provide a drug that is safe and can be taken every day and can significantly suppress allergic bronchial asthma.

  The inventor has made various studies to solve the above problems. As a result, the present inventors have found that the cocoon seed extract, which the present inventor has continued to research, has a remarkable inhibitory effect particularly on allergic bronchial asthma, thereby completing the present invention.

  The allergic bronchial asthma inhibitor of the present invention is characterized in that it contains an extract of persimmon seeds.

  As the extract, an alcohol water extract is preferable. This is because when alcoholic water is used as an extraction solvent, it is possible to extract evenly from a hydrophobic component to a hydrophilic component, and the antiallergic action of the extract is excellent.

  Although the mechanism of action by which the inhibitor according to the present invention suppresses allergic bronchial asthma is not necessarily clear, the inhibitor of the present invention increases the proliferation of lung goblet cells that cause cough by producing mucus in at least the lung. Has the effect of suppressing.

  Since the allergic bronchial asthma inhibitor of the present invention comprises a koji seed extract as a main active ingredient, it is excellent in safety and can be taken every day. In addition, various symptoms of allergic bronchial asthma and intercellular signal transduction substances that cause them can be remarkably suppressed. Therefore, the allergic bronchial asthma inhibitor of the present invention is extremely useful industrially as an excellent inhibitor of allergic bronchial asthma which has been a problem in recent years.

  The allergic bronchial asthma inhibitor of the present invention is characterized in that it contains an extract of persimmon seeds. In the present invention, “suppression” is a concept including all aspects for reducing the symptoms of allergic bronchial asthma, and includes, for example, prevention and treatment.

  Persimmon is an evergreen tree of the Rosaceae native to China. It is thought that it was brought into Japan in ancient times, and its fruit is also popular in Japan. Moreover, the leaf contains vitamin B17, citric acid, etc., and has been used as a tea or a herbal medicine. However, regarding the persimmon seeds, although the proportion of the persimmon fruit was large, its utilization method was hardly studied and discarded. On the other hand, the present inventor has found an excellent medicinal effect of persimmon seeds and has continued research. The present invention has been completed as part of the research.

  The cocoon seeds used in the present invention may be those obtained by removing skin and pulp from the fruit. Subsequently, washing and drying are performed for storage and efficient grinding. The drying conditions are not particularly limited. For example, in order to decompose amygdalin, which is a nitrile compound, with emuldin, which is a degrading enzyme, it is dried at about 40 ° C. for about one week.

  In order to make the extraction efficient, it is preferable to grind the cocoon seeds before the extraction. The method of pulverization is not particularly limited, and for example, a ball mill, a hammer mill, a roller mill, a rod mill, a sample mill, a stamp mill, an echs integrator, a blender with a cooling device, or the like can be used.

  Next, the active ingredient is extracted by immersing the pulverized camellia seeds in a solvent. The type of the extraction solvent is not particularly limited and can be appropriately selected in consideration of the type of allergic bronchial asthma that is a target and the effectiveness of the extracted components, but those that are harmless or less harmful to the living body are preferable. For example, water or a mixed solvent of water and a water-miscible organic solvent such as alcohol such as methanol or ethanol; ether such as tetrahydrofuran or dioxane; ketone such as acetone; Preferably, about 50 to 80% by volume of ethanol water is used. In addition, ethanol water here says the capacity | capacitance of ethanol: water 50: 50-80: 20.

  The immersion conditions can be adjusted as appropriate. For example, the amount of solvent to be used may be adjusted so that at least the pulverized camellia seeds are soaked evenly, and the extraction amount of the active ingredient and the efficiency at the time of concentration are taken into consideration. The extraction temperature is not particularly limited, and may be heated to about 30 to 50 ° C. in order to increase the extraction efficiency. However, since the active ingredient may be decomposed, it is preferably set to room temperature. Moreover, in order to improve extraction efficiency, you may stir a solvent. The extraction time may be adjusted as appropriate, but is usually about 5 to 10 days.

  After extraction, the residue of cocoon seeds is removed by filtration or the like. The obtained extract may be used as it is as an allergic bronchial asthma suppressant as it is depending on the solvent, but is preferably once concentrated or re-dissolved in a more suitable solvent in order to enhance storage stability. In the concentration treatment, it is preferable to reduce the pressure using an evaporator in order to suppress the concentration temperature and from the viewpoint of efficiency.

  The components extracted from the seeds and the amount thereof vary depending on the type of solvent used, but from 50 to 80% by volume of ethanol water as the extraction solvent, from highly polar compounds to relatively low polarity compounds. Can be extracted evenly.

  According to the study by the present inventors, the seed extract obtained using 70% ethanol water as an extraction solvent includes unsaturated fatty acids such as linolenic acid and linoleic acid, sterols such as β-sitosterol, and β-sitosterol. Sugar derivatives such as monoglycoside were included. In the present invention, it is not always clear which active ingredient has an antiallergic bronchial asthma action, but it is considered that a plurality of compounds are additively or synergistically effective.

  Since the extract according to the present invention is derived from cocoon seeds, it is considered to be highly safe. In fact, high safety has been confirmed in safety tests. Therefore, the allergic bronchial asthma inhibitor of the present invention can be used not only for the purpose of treating allergic bronchial asthma but also for the purpose of preventing allergic bronchial asthma by taking it constantly.

  The dosage of the allergic bronchial asthma inhibitor according to the present invention depends on the condition and age of the patient to be administered, and the composition of the extracted components. In rats, it should be administered at least about 375 mg / kg / day, but a smaller amount is preferable for humans. In any case, the dose may be appropriately adjusted depending on the patient's condition from the start of administration.

  To the extract according to the present invention, known formulation components can be added to obtain various formulations. For example, base materials, excipients, colorants, lubricants, flavoring agents, emulsifiers, thickeners, wetting agents, stabilizers, preservatives, solvents, solubilizers, suspending agents, antioxidants, Drugs, buffers, pH adjusters, sweeteners, fragrances and the like can be added. Moreover, the compounding quantity of these additives can be suitably set as needed as long as it is the quantity which does not prevent the effect of this invention.

  The dosage form can be a liquid, syrup, tablet, capsule, granule, suppository, or injection, but it is preferably an oral preparation such as a liquid in consideration of long-term administration.

  In the case of a solution, the coconut seed extract once concentrated and powdered is redissolved or redispersed in a solvent such as water. The concentration of the cocoon seed extract in this case is not particularly limited, and may be appropriately adjusted depending on the patient's condition and the like. For example, in terms of the concentration of the dried cocoon seed extract, about 2 to 80 g / L can do.

  As a solvent in the case of a liquid preparation, water suitable for human consumption is preferable. For example, distilled water, purified water, pure water, tap water, or the like may be used. A trace amount of ethanol or the like may be added.

  The allergic bronchial asthma inhibitor of the present invention can be applied to suppression of allergic bronchial asthma, that is, prevention or treatment. In particular, since the allergic bronchial asthma inhibitor of the present invention is highly safe, it can be used as a health food or a health drink to prevent allergic bronchial asthma by taking it constantly.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, but may be appropriately modified within a range that can meet the purpose described above and below. It is also possible to implement, and they are all included in the technical scope of the present invention.

Production Example 1 Production of Allergic Bronchial Asthma Inhibitor According to the Present Invention The persimmon seeds collected in Muroto City or Susaki City, Kochi Prefecture were sufficiently dried by sun drying. 1 kg of dried persimmon seeds was pulverized by a blender with a cooling device, immersed in 2 L of 70% ethanol water, and stirred at room temperature for 1 week. Thereafter, the liquid portion was collected and concentrated under reduced pressure using an evaporator. About 120 g of the obtained extract was dissolved in 200 mL of distilled water to produce the allergic bronchial asthma inhibitor according to the present invention.

Test example 1
Twenty-four male 5-week-old BALB / c mice were divided into the following groups of 6 mice each.
Group 1-Mite extract administration group Group 2-Mite extract + diesel vehicle exhaust gas extract (hereinafter referred to as "DEP") administration group Group 3-Anther seed extract + mite extract administration group Group 4 -Anther seed extract + mite extract + DEP administration group

  Moreover, a commercially available standard mite extract as an allergen was dissolved in physiological saline to prepare a solution having a concentration of 4 μg / 100 μL. Similarly, a commercially available DEP standard solid as an allergen extracted with methylene chloride was dissolved in DMSO to obtain a 200 mg / mL solution, which was further diluted with physiological saline to prepare a 62.5 μg / 100 μL solution. .

  First, tap water was freely given to the first group and the second group from 14 days before allergen administration, and the persimmon seed extract produced in Production Example 1 was freely given to the third group and the fourth group. Next, the mice were anesthetized with Nembutal, and the above-mentioned mite extract solution was administered into the trachea 10 times in a cannula, 100 μL each time, twice a week for 5 weeks. Furthermore, 100 μL of DEP solution was administered intratracheally to each of the second and fourth groups in the same manner. Immediately before allergen administration and the day before the even-numbered administration of the mite extract solution, 300 μL of blood was collected from the orbit and the mite antigen-specific IgG1 antibody titer, IL-13 amount and TGF-β1 amount were measured. In addition, two days after administration of the final tick extract solution, mice were euthanized by injecting an excessive amount of Nembutal, lung lavage fluid (BALF) was collected, and the number of eosinophils was measured. In addition, lungs were collected and stained with HE to prepare lung pathological tissue specimens. FIG. 1 shows the measurement result of the titer antigen-specific IgG1 antibody titer, FIG. 2 shows the measurement result of the IL-13 amount, FIG. 3 shows the measurement result of the TGF-β1 amount, and FIG. 4 shows the number of eosinophils in BALF. FIG. 5 shows a 20-fold enlarged photograph of a lung pathological tissue specimen.

  As shown in FIG. 1, the IgG1 antibody titer specific to mite antigens was increased especially when DEP was added as an allergen in addition to the mite extract, and a strong allergic reaction occurred. Administration of the extract significantly suppressed the antibody titer at a risk factor <0.05. As shown in FIGS. 2 to 3, IL-13 and mite extract induced by DEP or TGF-β1 induced by DEP are also significantly suppressed by administration of the anther seed extract according to the present invention. Since these increase the number of goblet cells that produce mucus due to allergic reaction in the bronchi, the results of FIGS. 2 to 3 provide evidence that the persimmon seed extract of the present invention suppresses allergic reaction. In addition, as shown in FIG. 4, although there was no significant difference, the anther seed extract of the present invention suppresses the differentiation activation of eosinophils in the lung increased by administration of DEP.

  Furthermore, as shown in FIG. 5, when DEP was added in addition to the mite extract, goblet cells increased on the surface of the lung, and even edema occurred. However, when gourd seed extract of the present invention is administered, these goblet cells and edema are remarkably suppressed.

  As described above, it has been demonstrated that the cocoon seed extract according to the present invention can remarkably suppress the symptoms of allergic bronchial asthma and the production of an intercellular signal transmitter involved in the occurrence thereof.

It is a figure which shows the measurement result of the tick antigen specific IgG1 antibody titer in the allergic bronchial asthma model mouse. It is a figure which shows the measurement result of the amount of IL-13 in serum of an allergic bronchial asthma model mouse. It is a figure which shows the measurement result of the amount of TGF- (beta) 1 in serum of an allergic bronchial asthma model mouse. It is a figure which shows the measurement result of the number of eosinophils in the lung lavage fluid (BALF) of an allergic bronchial asthma model mouse. It is a 20 times enlarged photograph of the pathological tissue specimen of the lung of an allergic bronchial asthma model mouse.

Explanation of symbols

  1: Goblet cells, 2: Edema

Claims (3)

  An allergic bronchial asthma inhibitor characterized by containing an extract of persimmon seeds.   The allergic bronchial asthma inhibitor according to claim 1, wherein the extract is an alcoholic water extract.   The allergic bronchial asthma inhibitor according to claim 1 or 2, which suppresses an increase in lung goblet cells.