Use of HMPA and / or its conjugates

Abstract

The present invention provides a drug containing HMPA and / or its conjugates that produces a novel physiological effect. [Solution] The agent of this disclosure comprises HMPA and / or its conjugate represented by the following formula. This agent can be used for the prevention and improvement of stress, the prevention and improvement of residual urine sensation, the prevention and improvement of sticky skin, the prevention and improvement of dry eyes, the promotion of appetite, and the like. [Case 1] JPEG2026085584000014.jpg37139

Description

Technical Field

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[0001] The present invention relates to the use of HMPA and / or its conjugates.

Background Art

[0002] 3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA) is known to have various physiological activities. For example, Patent Document 1 discloses a corneal epithelial cell growth promoter containing HMPA, a glutathione production promoter in corneal epithelial cells, and a corneal epithelial repair promoter.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] [[ID=​​​​​​​​​​​​​​​​​​​​​​​​ <3> An agent for preventing and improving the feeling of residual urine, comprising HMPA and / or its conjugate represented by the following formula. [ka] <4> <3> A composition for preventing and improving the feeling of residual urine, containing the agent for preventing and improving the feeling of residual urine described above. <5> A skin oiliness prevention and improvement agent containing HMPA and / or its conjugates, represented by the following formula. [ka] <6> <5> A composition for preventing and improving skin stickiness, containing the skin stickiness prevention and improvement agents described above. <7> A dry eye preventative and ameliorative agent containing HMPA and / or its conjugate, represented by the following formula. [ka] <8> <7> A composition for preventing and improving dry eye, containing the dry eye prevention and improvement agent described above. <9> An appetite stimulant containing HMPA and / or its conjugates, represented by the following formula. [ka] <10> <9> An appetite-stimulating composition containing the appetite-stimulating agent described above. [Effects of the Invention]

[0007] According to one aspect of the present invention, an agent comprising HMPA and / or its conjugate is provided that produces a novel physiological effect. [Modes for carrying out the invention]

[0008] Hereinafter, an example of an embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and various modifications may be made within the scope indicated in the claims. Embodiments combining technical means described in different embodiments are also included in the technical scope of the present invention.

[0009] Unless otherwise specified in this specification, "A~B" representing a numerical range means "A or more and B or less".

[0010] In this specification, 3-(4-hydroxy-3-methoxyphenyl)propionic acid is abbreviated as "HMPA". HMPA may also be referred to as "dihydroferulic acid" by its common name.

[0011] [1. Agent containing HMPA] The first aspect of the present invention is a stress prevention / improvement agent containing HMPA and / or its conjugate. The second aspect of the present invention is a residual urine feeling prevention / improvement agent containing HMPA and / or its conjugate. The third aspect of the present invention is a skin stickiness prevention / improvement agent containing HMPA and / or its conjugate. The fourth aspect of the present invention is a dry eye prevention / improvement agent containing HMPA and / or its conjugate. The fifth aspect of the present invention is an appetite enhancer containing HMPA and / or its conjugate.

[0012] [1.1. HMPA or its conjugate] In any of the above aspects, HMPA is a compound represented by the following chemical formula. [Chemical formula]

[0013] The agent may contain HMPA conjugates. In this case, the agent may contain only one type of HMPA conjugate or two or more types. An HMPA conjugate is a compound in which a water-soluble molecule is added to HMPA. Examples of water-soluble molecules that can form conjugates include sulfuric acid, glucuronic acid, glutathione, and amino acids. In one embodiment, the water-soluble molecule is sulfuric acid and / or glucuronic acid. The number of water-soluble molecules that bind to one HMPA molecule in the conjugate is not particularly limited. In one embodiment, the number of water-soluble molecules that bind to one HMPA molecule is one. In the conjugate, the site where the water-soluble molecule binds to HMPA is not particularly limited. In one embodiment, the water-soluble molecule is bound via the hydroxyl group at position 4 of the benzene ring of the HMPA molecule.

[0014] In one embodiment, the HMPA conjugate is a compound represented by A and / or B below. A is a conjugate in which sulfuric acid is bonded via the hydroxyl group at position 4 of the benzene ring of the HMPA molecule. B is a conjugate in which glucuronic acid is bonded via the hydroxyl group at position 4 of the benzene ring of the HMPA molecule. [ka]

[0015] HMPA and its conjugates are known compounds. Therefore, those skilled in the art can easily produce, extract, or purchase HMPA or its conjugates to manufacture the agent.

[0016] The lower limit of the total amount of HMPA and its conjugates contained in the agent, converted to HMPA and with the total weight of the agent as 100% by weight, may be 0.0001% or more, 0.0005% or more, 0.001% or more, 0.005% or more, 0.01% or more, 0.05% or more, 0.1% or more, 0.5% or more, 1% or more, 5% or more, 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, or 90% or more by weight. The lower limit of the total amount of HMPA and its conjugates contained in the agent, converted to HMPA and with the total weight of the agent as 100% by weight, may be 0.0001% by weight or less, 0.0005% by weight or less, 0.001% by weight or less, 0.005% by weight or less, 0.01% by weight or less, 0.05% by weight or less, 0.1% by weight or less, 0.5% by weight or less, 1% by weight or less, 5% by weight or less, 10% by weight or less, 20% by weight or less, 30% by weight or less, 40% by weight or less, 50% by weight or less, 60% by weight or less, 70% by weight or less, 80% by weight or less, 90% by weight or less, or 100% by weight or less. In one embodiment, the agent consists only of HMPA and / or its conjugates.

[0017] The agent can be manufactured according to conventional methods. Methods for incorporating HMPA and / or its conjugates into the agent are well known to those skilled in the art.

[0018] [1.2. Other Ingredients] The agent may contain components other than HMPA and / or its conjugates. These other components may consist of only one type or two or more types. The amount of these other components in the agent is not particularly limited.

[0019] Other examples of ingredients include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, deodorizing agents, moisture-proofing agents, preservatives, fortifiers, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, colorants, fragrances, whitening agents, moisturizers, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, colorants, aqueous components, water, and skin nutrients. The agent may contain only one of the above-mentioned other components, or it may contain a combination of two or more substances.

[0020] [1.3. Effects of the agent] Stress preventive and ameliorative agents prevent and / or improve stress in subjects to whom they are administered. That is, subjects to whom stress preventive and ameliorative agents are administered experience prevention and / or improvement of stress. In this specification, “prevention of stress” means not only complete suppression of the future occurrence of stress-related symptoms, but also mitigation of stress-related symptoms that may occur in the future. In this specification, “improvement of stress” means not only complete recovery from stress-related symptoms that have occurred, but also mitigation of stress-related symptoms that have occurred. In one embodiment, the degree of stress is evaluated by subjective indicators of the subject. In other embodiments, the degree of stress is evaluated by objective indicators such as the subject’s behavior or physiological state.

[0021] The urinary retention prevention and improvement agent prevents and / or improves the feeling of incomplete bladder emptying in the administered subject. That is, subjects administered with the urinary retention prevention and improvement agent experience prevention and / or improvement of the feeling of incomplete bladder emptying. In this specification, "prevention of urinary retention" means not only complete suppression of future urinary retention, but also mitigation of urinary retention that may occur in the future. In this specification, "improvement of urinary retention" means not only complete recovery from existing urinary retention, but also mitigation of existing urinary retention. In one embodiment, the degree of urinary retention is evaluated by subjective indicators of the subject. In other embodiments, the degree of urinary retention is evaluated by objective indicators such as the subject's behavior or physiological state.

[0022] A skin oiliness prevention and improvement agent prevents and / or improves skin oiliness in subjects to whom it is administered. That is, subjects to whom a skin oiliness prevention and improvement agent is administered experience prevention and / or improvement of skin oiliness. In this specification, "prevention of skin oiliness" means not only complete suppression of future skin oiliness but also mitigation of skin oiliness that may occur in the future. In this specification, "improvement of skin oiliness" means not only complete recovery from existing skin oiliness but also mitigation of existing skin oiliness. In one embodiment, the degree of skin oiliness is evaluated by subjective indicators of the subject. In other embodiments, the degree of skin oiliness is evaluated by objective indicators such as the subject's behavior or physiological state.

[0023] Dry eye preventive and ameliorative agents prevent and improve dry eye in subjects to whom they are administered. That is, subjects to whom dry eye preventive and ameliorative agents are administered have their dry eye prevented and / or improved. In this specification, "prevention of dry eye" means not only the complete suppression of the future onset of dry eye symptoms, but also the alleviation of dry eye symptoms that occur in the future. In this specification, "improvement of dry eye" means not only complete recovery from dry eye that is currently present, but also the alleviation of dry eye symptoms that are currently present.

[0024] Appetite stimulants increase the appetite of subjects to whom they are administered. That is, subjects who are administered an appetite stimulant experience increased appetite after administration. In one embodiment, the degree of appetite is evaluated using subjective indicators of the subject. In other embodiments, the degree of appetite is evaluated using objective indicators such as the subject's behavior or physiological state.

[0025] In one embodiment, the subject is a mammal. In one embodiment, the subject is a human or a non-human mammal. Examples of non-human mammals include mice, rats, hamsters, dogs, cats, cows, pigs, and monkeys.

[0026] Examples of methods of administering the drug include oral administration, parenteral administration, and topical administration.

[0027] [2. Compositions containing the agent] A sixth aspect of the present invention is a stress prevention and improvement composition containing the above-mentioned stress prevention and improvement agent. A seventh aspect of the present invention is a stress prevention and improvement composition containing the above-mentioned residual urine sensation prevention and improvement agent. A eighth aspect of the present invention is a skin stickiness prevention and improvement composition containing the above-mentioned skin stickiness prevention and improvement agent. A ninth aspect of the present invention is a dry eye prevention and improvement composition containing the above-mentioned dry eye prevention and improvement agent. A tenth aspect of the present invention is an appetite-stimulating composition containing the above-mentioned appetite-stimulating agent.

[0028] For example, an agent according to one aspect of the present invention is distributed to manufacturers as a material that provides a specific physiological function (such as an active pharmaceutical ingredient or functional material). For example, a composition according to one aspect of the present invention is distributed to consumers as a specific product containing the agent (such as a pharmaceutical product, quasi-drug, food and beverage, or cosmetic). However, the above are illustrative examples, and in reality, agents and compositions may be manufactured and distributed in a wide variety of forms.

[0029] The lower limit of the total amount of agents contained in the composition may be 0.0001% by weight or more, 0.0005% by weight or more, 0.001% by weight or more, 0.005% by weight or more, 0.01% by weight or more, 0.05% by weight or more, 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 5% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, 70% by weight or more, 80% by weight or more, or 90% by weight or more, with the total weight of the composition being 100% by weight. The upper limit of the total amount of the agent contained in the composition may be 0.0001% by weight or less, 0.0005% by weight or less, 0.001% by weight or less, 0.005% by weight or less, 0.01% by weight or less, 0.05% by weight or less, 0.1% by weight or less, 0.5% by weight or less, 1% by weight or less, 5% by weight or less, 10% by weight or less, 20% by weight or less, 30% by weight or less, 40% by weight or less, 50% by weight or less, 60% by weight or less, 70% by weight or less, 80% by weight or less, 90% by weight or less, or 100% by weight or less, with the total weight of the composition being 100% by weight. In one embodiment, the composition consists only of the agent.

[0030] The composition may contain other components in addition to the agent. Examples of other components are those exemplified in Section [1.2]. The content of other components is not particularly limited.

[0031] [2.1. Form of composition] Examples of administration routes for compositions include oral administration, parenteral administration, and topical administration. Below, specific forms of compositions are illustrated according to these administration routes. Note that these specific forms may be classified as pharmaceuticals, quasi-drugs, food and beverages, cosmetics, general merchandise, etc., according to laws, administrative regulations, or common practice.

[0032] Examples of compositions administered externally include ointments, lotions, emulsions, creams, serums, gels, beauty oils, masks, jellies, lip balms, lipsticks, foundations, bath additives, soaps, body washes, astringents, hair tonics, hair lotions, hair creams, hair liquids, pomades, shampoos, rinses, conditioners, eye drops, and eye washes.

[0033] Examples of compositions administered parenterally include injections, intravenous infusions, and suppositories.

[0034] Examples of orally administered compositions include: beverages (tea beverages, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, alcoholic beverages, coffee beverages, coffee-flavored soft drinks, etc.); concentrated stocks and powders for preparing these beverages; frozen desserts (ice cream, ice sherbet, shaved ice, etc.); noodles (soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, instant noodles, etc.); confectionery (candy, gum, chocolate, tablets, snacks, biscuits, jelly, jam, cream, baked goods, bread, etc.); marine products (crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oyster, saury, squid, ark clam, scallop, abalone, sea urchin, salmon roe, tokobushi, etc.); and processed marine and livestock products (kamaboko, ham, sausage, etc.). Examples of products include: dairy products (processed milk, fermented milk, etc.); oils and fats and processed oils (salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings, etc.); seasonings (sauces, dips, etc.); retort pouch foods (curry, stew, oyakodon, porridge, rice gruel, chukadon, katsudon, tempuradon, unadon, hayashi rice, oden, mapo tofu, gyudon, meat sauce, egg soup, omurice, gyoza, shumai, hamburgers, meatballs, etc.); prepared foods (salads, pickles, etc.); health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs (tablets, powders, capsules, granules, extracts, syrups, drinks, lozenges, mouthwash, etc.); oral fresheners (mouth fresheners, bad breath preventatives, etc.); and toothpaste.

[0035] The composition may be used as a research reagent. For example, the composition for preventing or improving dry eye may be used to study the mechanism by which dry eye is prevented or improved.

[0036] These compositions can be manufactured according to conventional methods. Methods for incorporating the agents into the compositions are well known to those skilled in the art.

[0037] [2.2. Function of the composition] The stress prevention and improvement composition prevents and / or improves stress in subjects who receive it. The bladder retention prevention and improvement composition prevents and / or improves the feeling of incomplete bladder emptying in subjects who receive it. The skin stickiness prevention and improvement composition prevents and / or improves skin stickiness in subjects who receive it. The dry eye prevention and improvement composition prevents and / or improves dry eye in subjects who receive it. The appetite-stimulating composition increases the appetite of subjects who receive it. These effects and subjects are as described in Section [1.3]. [Examples]

[0038] [Experimental Design] Eight subjects (average age 54.6 years) were given a food product containing HMPA on a continuous basis. Specifically, they took one capsule orally per day, with a daily HMPA intake of 23 mg, for a period of 12 weeks.

[0039] A questionnaire survey was conducted regarding the following five points before the start of intake, 6 weeks after the start of intake, and 12 weeks after the start of intake. Q1. No stress Q2. I feel like I still have urine left inside. Q3. My skin feels sticky. Q4. I have dry eyes. Q5. I have no appetite.

[0040] Each question was answered using a 7-point subjective scale. The answer choices were as follows. For each question, a lower numbered option indicated a more desirable state, and a higher numbered option indicated a less desirable state. • Answer choices for Q1 1. I strongly agree. 2. I think so. 3. I somewhat agree. 4. Neither agree nor disagree 5. I don't really think so. 6. I don't think so. 7. I don't think so at all. • Answer choices for Q2-5 1. I don't think so at all. 2. I don't think so. 3. I don't really think so. 4. Neither agree nor disagree 5. I somewhat agree. 6. I think so. 7. I strongly agree.

[0041] 〔result〕 The results are shown in Table 1 below. Table 1 shows the mean, standard deviation, and median of the answer choices selected by the subjects for each question. [Table 1]

[0042] In all questions, there was a tendency for the selected option number to decrease after HMPA intake. In particular, for Q1, Q3, and Q4, the longer the period of HMPA intake, the more likely it was that the selected option number would decrease. These results indicate that HMPA intake provides physiological effects such as prevention and improvement of stress, prevention and improvement of residual urine sensation, prevention and improvement of oily skin, prevention and improvement of dry eyes, and increased appetite. [Industrial applicability]

[0043] One aspect of the present invention can be used for preventing and improving stress, preventing and improving the feeling of incomplete bladder emptying, preventing and improving sticky skin, preventing and improving dry eyes, and so on.

Claims

1. A stress preventative and ameliorative agent containing HMPA and / or its conjugates, represented by the following formula. 【Chemistry 1】

2. A composition for preventing and improving stress, comprising the stress prevention and improvement agent described in claim 1.

3. An agent for preventing and improving the feeling of residual urine, comprising HMPA and / or its conjugate represented by the following formula. 【Chemistry 2】

4. A composition for preventing and improving the feeling of residual urine, comprising the agent for preventing and improving the feeling of residual urine described in claim 3.

5. A skin oiliness prevention and improvement agent containing HMPA and / or its conjugates, represented by the following formula. 【Transformation 3】

6. A composition for preventing and improving skin stickiness, comprising the skin stickiness prevention and improvement agent described in claim 5.

7. A dry eye preventative and ameliorative agent containing HMPA and / or its conjugate, represented by the following formula. 【Chemistry 4】

8. A composition for preventing and improving dry eye, comprising the dry eye prevention and improvement agent described in claim 7.

9. An appetite stimulant comprising HMPA and / or its conjugates represented by the following formula. 【Transformation 5】

10. An appetite-stimulating composition comprising the appetite-stimulating agent described in claim 9.

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