Agent for normalizing the secretion of appetite-regulating hormones

Abstract

To provide agents that can improve the abnormal secretion of appetite-regulating hormone itself for the symptoms caused by the abnormal secretion of appetite-regulating hormone.SOLUTION: Since Daisaikoto extract has the effect of normalizing appetite-regulating hormone secretion, it is an active ingredient of an appetite-regulating hormone secretion normalizing agent. In addition, Daisaikoto extract is also effective as an active ingredient of a leptin resistance improving agent and can be used for the purpose of improving sleep disorders, dysgeusia, and / or reproductive dysfunction.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent capable of improving abnormal secretion of an appetite-regulating hormone itself for symptoms caused by abnormal secretion of an appetite-regulating hormone.

Background Art

[0002] Appetite-regulating hormones such as leptin are known as hormones that regulate appetite by acting within the hypothalamus. Recent studies have revealed that the action site of leptin is not only the hypothalamus, and that appetite is not the only biological effect of leptin.

[0003] Based on research on abnormal blood leptin secretion in obese patients and the effects of leptin administration to obese patients, it is known that there is "leptin resistance" in which the physiological function of leptin is not exerted despite a high blood leptin concentration. Due to the diversity of the biological effects of leptin, symptoms related to leptin resistance include not only obesity, but also deterioration of sleep quality (Non-Patent Document 1) due to an increase in slow-wave sleep and an increase in sleep fragmentation, taste disorders (Non-Patent Document 2) in which it becomes difficult to feel sweetness, and reproductive function disorders (Non-Patent Document 3) such as female ovulation, pregnancy, and childbirth.

[0004] As a first option for leptin resistance, attempts have been made to administer leptin as an active ingredient. There was a time when it was considered effective to administer leptin for obesity, but the effects are very limited. On the other hand, it has been reported that the above-mentioned taste disorders and the above-mentioned reproductive function disorders were improved by administration of leptin (Non-Patent Document 2 and Non-Patent Document 3).

[0005] On the other hand, leptin resistance improvers have also been reported for the purpose of fundamentally solving the constitution of leptin resistance itself. For example, a leptin resistance improver containing a neurotrophic factor or a ligand of the trk receptor as an active ingredient (Patent Document 1), a leptin resistance improver containing diacylglycerol as an active ingredient (Patent Document 2), a leptin resistance improver containing siglyceride as an active ingredient (Patent Document 3), and a leptin resistance improver containing a GABAB receptor agonist as an active ingredient (Patent Document 4) can be mentioned. These leptin resistance improvers reduce the blood concentration of leptin.

Prior Art Documents

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Patent Documents

[0007]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0008] In order to fundamentally solve each symptom caused by abnormal secretion of appetite regulating hormones, it is desirable to improve the abnormal secretion of appetite regulating hormones itself, such as a leptin resistance improver, and a new material that brings about such an effect is required.

[0009] An object of the present invention is to provide an agent that can improve the abnormal secretion of appetite regulating hormones itself with respect to symptoms caused by abnormal secretion of appetite regulating hormones.

Means for Solving the Problems

[0010] As a result of intensive studies, the present inventor has found that an extract of Sho-saiko-to can improve the abnormal secretion of appetite regulating hormones itself with respect to symptoms caused by abnormal secretion of appetite regulating hormones. The present invention has been completed by further studies based on such findings.

[0011] That is, the present invention provides an invention in the following aspects. Item 1. An agent for normalizing the secretion of appetite regulating hormones, containing an extract of Sho-saiko-to. Item 2. The agent for normalizing the secretion of appetite regulating hormones according to Item 1, wherein the appetite regulating hormone is leptin. Item 3. An agent for improving leptin resistance, containing an extract of Sho-saiko-to. Item 4. The agent for improving leptin resistance according to Item 3, which is used for improving sleep disorder, taste disorder, and / or reproductive function disorder.

Effects of the Invention

[0012] According to the present invention, an agent that can improve the abnormal secretion of appetite regulating hormones itself with respect to symptoms caused by abnormal secretion of appetite regulating hormones is provided.

Modes for Carrying Out the Invention

[0013] 1. Agent for normalizing the secretion of appetite-regulating hormones The agent for normalizing the secretion of appetite regulating hormones of the present invention is characterized by containing an extract of Sho-saiko-to. Hereinafter, the agent for normalizing the secretion of appetite regulating hormones of the present invention will be described in detail.

[0014] Extract of Sho-saiko-to As a Kampo prescription for Daisaikoto, the Kampo prescription described in "New Guide to General Kampo Prescriptions" (supervised by Yukihiro Goda and Takashi Hakamzuka, edited by the Japan Kampo Herbal Medicine Preparation Association, published by Jiho Co., Ltd.) is preferable, and specifically, a mixture of herbs consisting of Bupleurum Root, Pinellia Root, Scutellaria Root, Pheasant's Eye, Peony Root, Shokyo Root, Taisou Root, and Daio Root can be mentioned. In addition, Daisaikoto includes the mixture of herbs (Kampo prescriptions) described in currently used Kampo-related letters, as stipulated in the "Basic Handling Policy for Kampo Preparations" established by the Kampo Herbal Medicine Investigation Committee.

[0015] The amounts of each herb that makes up Daisaikoto include 3 to 12 parts by weight, preferably 4 to 9 parts by weight, of Bupleurum Root; 2 to 8 parts by weight, preferably 2.5 to 6 parts by weight, of Pinellia Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Scutellaria Root; 1 to 4 parts by weight, preferably 1.5 to 3 parts by weight, of Pheasant's Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Peony Root; 0.5 to 2 parts by weight, preferably 1 to 1.5 parts by weight, of Zingiber Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Taiso Root; and 0.5 to 2 parts by weight, preferably 1 to 1.5 parts by weight.

[0016] The extract form of Daisaikoto may be either a liquid extract such as a soft extract, or a solid dry extract powder.

[0017] The liquid extract of Daisaikoto can be obtained by subjecting a mixture of herbal medicines according to the Daisaikoto prescription to an extraction process and concentrating the resulting extract as necessary. The dried extract powder of Daisaikoto can be obtained by drying the liquid extract.

[0018] In the production of the extract of Sho-saiko-to, the extraction solvent used in the extraction process is not particularly limited, but preferred examples include water or aqueous ethanol. The method for extracting Sho-saiko-to is not particularly limited. For example, a method can be mentioned in which the crude drugs constituting Sho-saiko-to are extracted with an extraction solvent and then concentrated to remove the solid content to obtain a liquid extract of Sho-saiko-to. Further, by subjecting this liquid extract to a drying treatment, a dried extract powder of Sho-saiko-to can be obtained. The drying treatment is not particularly limited, and a known method may be used. For example, a spray drying method or a method in which a suitable adsorbent (such as anhydrous silicic acid, starch, etc.) is added to a soft extract with an increased extract concentration to obtain an adsorbed powder can be mentioned.

[0019] When using an extract as Sho-saiko-to in the present invention, an extract prepared by the aforementioned method may be used, or a commercially available product may be used. For example, as the dried extract powder of Sho-saiko-to, Sho-saiko-to Dried Extract AM, Sho-saiko-to Dried Extract SN, and Sho-saiko-to Dried Extract Powder (all manufactured by Nippon Powder Co., Ltd.), as well as Sho-saiko-to Dried Extract F and Sho-saiko-to Dried Extract -F (both manufactured by Alps Pharmaceutical Co., Ltd.) are known as products and can be commercially obtained.

[0020] In the appetite-regulating hormone secretion normalizing agent of the present invention, the content of the Sho-saiko-to extract is not particularly limited as long as the effects of the present invention are achieved. However, in terms of the amount of the dried extract powder of the Sho-saiko-to extract, it is usually 5 to 100% by weight, preferably 10 to 90% by weight, more preferably 20 to 80% by weight, and still more preferably 30 to 60% by weight. In the present invention, the conversion in terms of the amount of the dried extract powder of Sho-saiko-to means the amount itself when using the dried extract powder of Sho-saiko-to, and when using the liquid extract of Sho-saiko-to, it is the amount converted to the remaining amount after removing the solvent. Further, when the dried extract powder of Sho-saiko-to contains additives such as adsorbents added during production, it is the amount excluding the additives.

[0021] Other components The appetite-regulating hormone secretion normalizing agent of the present invention may consist of only the extract of Sho-saiko-to, or may contain additives and bases according to the dosage form. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable. For example, excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, gloss agents, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, ultraviolet ray protectants, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, etc. may be mentioned. These additives may be used alone or in combination of two or more. Also, the content of these additives and bases is appropriately set according to the type of additives and bases used, the dosage form of the appetite-regulating hormone secretion normalizing agent, etc.

[0022] In addition to the extract of Sho-saiko-to, the appetite-regulating hormone secretion normalizing agent of the present invention may contain other nutritional components and pharmacological components as necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable. For example, antacids, stomachics, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeine compounds, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drug extracts, vitamins, menthol compounds, etc. may be mentioned. These nutritional components and pharmacological components may be used alone or in combination of two or more. Also, the content of these components is appropriately set according to the type of components used, etc.

[0023] Form of preparation The dosage form of the appetite-regulating hormone secretion normalizer of the present invention is not particularly limited as long as it can be administered orally, and examples thereof include solid preparations such as powders, fine granules, granules (including dry syrup), tablets, pills, capsules (soft capsules, hard capsules), etc.; semi-solid preparations such as jellies; and liquid preparations such as liquids, suspensions, syrups, etc. Among these dosage forms, solid preparations are preferred from the viewpoints of the stability and portability of the contained ingredients.

[0024] To prepare the appetite-regulating hormone secretion normalizer of the present invention in the above-mentioned formulation form, Daisaikoto extract, and additives, bases, and pharmacological ingredients added as necessary may be used to formulate the agent in accordance with conventional formulation methods used in the pharmaceutical field.

[0025] Uses The appetite-regulating hormone secretion normalizing agent of the present invention can be used for the purpose of improving the abnormal secretion of appetite-regulating hormones themselves, in relation to symptoms caused by abnormal secretion of appetite-regulating hormones. An example of the appetite-regulating hormone is leptin.

[0026] More specifically, the appetite-regulating hormone secretion normalizing agent of the present invention can be used for the purpose of reducing the amount of leptin in the blood to a normal level in the case of leptin resistance, which is an excessive amount of leptin secreted in the blood.

[0027] Symptoms to which the appetite-regulating hormone secretion normalizing agent of the present invention is applicable include leptin resistance, and further include obesity, sleep disorder, taste disorder, and reproductive dysfunction, which are symptoms caused by leptin resistance. Specific examples of sleep disorders include symptoms in which sleep quality is deteriorated due to an increase in slow wave sleep and / or an increase in sleep fragmentation. Examples of taste disorders include taste disorders in which sweetness, one of the five tastes, is difficult to sense. Examples of reproductive dysfunction include disorders related to ovulation, pregnancy, and childbirth in women.

[0028] Dosage and administration The appetite-regulating hormone secretion normalizing agent of the present invention is used by oral administration. Regarding the dosage of the appetite-regulating hormone secretion normalizing agent of the present invention, it is appropriately set according to the age, gender, constitution, etc. of the administration subject. For example, for one human, it is about 1 to 15 g in terms of the dry extract powder amount conversion of the Bupleurum and Scutellaria Decoction extract per day, and it may be taken 1 to 3 times a day, preferably 2 or 3 times. Regarding the administration timing, there is no particular limitation, and it may be before a meal, after a meal, or between meals, but before a meal (30 minutes before a meal) or between meals (2 hours after a meal) is preferred.

[0029] Also, from the viewpoint of more effectively obtaining the normalization of appetite-regulating hormone secretion, it is preferably taken continuously for, for example, 1 week or more, preferably 4 weeks or more, more preferably 8 weeks or more.

[0030] 2. Agent for improving leptin resistance The Bupleurum and Scutellaria Decoction can improve leptin resistance. Therefore, the present invention also provides a leptin resistance improving agent. Also, as described above, symptoms caused by leptin resistance include obesity, sleep disorder, taste disorder, and reproductive function disorder. Therefore, the leptin resistance improving agent of the present invention can be used to improve sleep disorder, taste disorder, and / or reproductive function disorder.

[0031] Regarding the active ingredient, content, dosage form, dosage, etc. in the leptin resistance improving agent, they are the same as those in the above-mentioned "1. Appetite-regulating hormone secretion normalizing agent".

Examples

[0032] Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

[0033] Preparation of Sho-saiko-to powder The raw herbs were used in the ratio of 6.0 (parts by weight, the same below), 4.0 (parts by weight), 1.0 (parts by weight), 3.0 (parts by weight), 3.0 (parts by weight), 3.0 (parts by weight) of Peony Root, 3.0 (parts by weight), 3.0 (parts by weight) of Chinese Peony Root, 3.0 (parts by weight), 2.0 (parts by weight), and 1.0 (parts by weight) of Rhizome. After chopping, they were extracted with 20 times the weight of water (460 parts by weight) at about 100°C for 1 hour, centrifuged to obtain an extract, which was concentrated under reduced pressure and dried using a spray dryer to obtain Daisaikoto extract powder. The obtained Daisaikoto extract powder was 2.4g per 13.8g of raw herb mixture. The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0034] Test examples Female ddY mice were used, and were allowed to give birth at the age of 10 weeks. After a one-week recovery period, they were fed a high-fat diet (High Fat Diet 32, manufactured by CLEA Japan) for two weeks to create leptin-resistant model mice. The leptin-resistant model mice were allowed to freely feed on a high-fat diet without Daisaikoto extract (DSK) or a high-fat diet containing 2% or 4% by weight of Daisaikoto extract (DSK) for eight weeks (N=6 for each group). For comparison, non-pregnant female ddY mice (normal mice) of the same age were also allowed to freely feed on a high-fat diet for eight weeks (N=6). After eight weeks of feeding, the amount of food consumed was calculated and the amount of leptin in the blood was measured, and the average value was calculated for each. In addition, the group fed with the DSK-free diet was compared with the group fed with the DSK 2% mixed diet and the group fed with the DSK 4% mixed diet using the Dunnett method. The results are shown in Table 1.

[0035] [Table 1]

[0036] As shown in Table 1, leptin-resistant model mice showed an abnormal increase in blood leptin levels. However, by administering Daisaikoto extract (DSK), there was no increase in food intake, while blood leptin levels were significantly reduced compared to the group fed a diet not containing DSK, demonstrating improvement in leptin resistance.

Claims

【Claim 1】 A leptin secretion normalizing agent containing an extract of Sho-saiko-to.

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