JP7699432B2 - Appetite regulating hormone secretion normalizer - Google Patents

Description

The present invention relates to an agent that can improve the abnormal secretion of appetite-regulating hormones itself, in order to treat symptoms caused by abnormal secretion of appetite-regulating hormones.

Appetite-regulating hormones such as leptin are known to regulate appetite by acting in the hypothalamus. Recent research has revealed that the hypothalamus is not the only site of action of leptin, and that appetite is not the only biological effect of leptin.

As a result of research into abnormal blood leptin secretion in obese patients and the effects of administering leptin to obese patients, it has become known that there exists "leptin resistance," in which the physiological functions of leptin are not exerted despite high blood leptin concentrations. Due to the diversity of leptin's biological effects, symptoms associated with leptin resistance include not only obesity, but also deterioration of sleep quality due to increased slow-wave sleep and increased sleep fragmentation (Non-Patent Document 1), taste disorders that make it difficult to sense sweetness (Non-Patent Document 2), and reproductive dysfunction in females, such as ovulation, pregnancy, and childbirth (Non-Patent Document 3).

As a first choice for leptin resistance, attempts have been made to administer leptin as an active ingredient. There was a time when administering leptin was thought to be effective for obesity, but the effects were very limited. On the other hand, it has been reported that the above-mentioned taste disorders and reproductive dysfunctions have been improved by administering leptin (Non-Patent Documents 2 and 3).

On the other hand, leptin resistance improvers have also been reported with the aim of fundamentally solving the leptin resistance constitution itself. For example, leptin resistance improvers that contain a neurotrophic factor or a TRK receptor ligand as an active ingredient (Patent Document 1), leptin resistance improvers that contain diacylglycerol as an active ingredient (Patent Document 2), leptin resistance improvers that contain diglyceride as an active ingredient (Patent Document 3), and leptin resistance improvers that contain a GABAB receptor agonist as an active ingredient (Patent Document 4) can be mentioned. These leptin resistance improvers reduce the blood concentration of leptin.

Int J Obes (Lond). 2010 Nov; 34(11): 1576-1588. Proc.Natl.Acad.Sci.,2000,97:11044-11049 Nat. Genet., 1996, 12:318-320

Retable No. 01/066133 JP 2002-003376 A JP 2002-322052 A Re-table 2008/018275 publication

To fundamentally resolve the various symptoms caused by abnormal secretion of appetite-regulating hormones, it is desirable to improve the abnormal secretion of appetite-regulating hormones themselves, as with leptin resistance improvers, and new materials that can achieve this effect are needed.

The object of the present invention is to provide an agent capable of improving the abnormal secretion of appetite-regulating hormones themselves, in order to treat symptoms caused by abnormal secretion of appetite-regulating hormones.

After extensive research, the inventors discovered that Daisaikoto extract can improve the abnormal secretion of appetite-regulating hormones themselves, in the case of symptoms caused by abnormal secretion of appetite-regulating hormones. The present invention was completed based on this finding and through further research.

That is, the present invention provides the following aspects.
Item 1. An appetite-regulating hormone secretion normalizer containing Daisaikoto extract.
Item 2. The appetite-regulating hormone secretion normalizing agent according to Item 1, wherein the appetite-regulating hormone is leptin.
Item 3. A leptin resistance improving agent containing Daisaikoto extract.
Item 4. The leptin resistance improving agent according to Item 3, which is used for improving sleep disorder, taste disorder, and/or reproductive dysfunction.

The present invention provides an agent that can improve the abnormal secretion of appetite-regulating hormones themselves, in response to symptoms caused by abnormal secretion of appetite-regulating hormones.

1. Appetite-regulating hormone secretion normalizer The appetite-regulating hormone secretion normalizer of the present invention is characterized by containing Daisaikoto extract. The appetite-regulating hormone secretion normalizer of the present invention will be described in detail below.

Daisaikoto Extract Daisaikoto is preferably prescribed in the "New Guide to General Kampo Prescriptions" (edited by Goda Yukihiro and Hakamzuka Takashi, edited by the Japan Kampo Herbal Medicine Preparation Association, published by Jiho Co., Ltd.), and specifically includes mixed herbs consisting of Bupleurum Root, Pinellia Root, Scutellaria Root, Pheasant's Root, Peony Root, Ginger Root, Chinese Herbal Medicine, and Daio. Daisaikoto also includes mixed herbs (herbal prescriptions) that are currently used in Kampo-related letters, as stipulated in the "Basic Handling Policy for Kampo Preparations" established by the Kampo Herbal Medicine Investigation Committee.

The amounts of each herb that makes up Daisaikoto include: Bupleurum Root 3-12 parts by weight, preferably 4-9 parts by weight; Pinellia Root 2-8 parts by weight, preferably 2.5-6 parts by weight; Scutellaria Root 1.5-6 parts by weight, preferably 2-4.5 parts by weight; Pheasant's Root 1-4 parts by weight, preferably 1.5-3 parts by weight; Peony Root 1.5-6 parts by weight, preferably 2-4.5 parts by weight; Shokyo Root 0.5-2 parts by weight, preferably 1-1.5 parts by weight; Taisou Root 1.5-6 parts by weight, preferably 2-4.5 parts by weight; and Daio Root 0.5-2 parts by weight, preferably 1-1.5 parts by weight.

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

The liquid extract of Daisaikoto can be obtained by subjecting the mixed herbs 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.

In the production of Daisaikoto extract, the extraction solvent used in the extraction process is not particularly limited, but suitable examples include water or aqueous ethanol. The method of extracting Daisaikoto is not particularly limited, but for example, the component herbs of Daisaikoto are extracted with an extraction solvent, and then concentrated and solids are removed to obtain a liquid extract of Daisaikoto. This liquid extract can be dried to obtain a dried extract powder of Daisaikoto. The drying process is not particularly limited, and any known method can be used, such as a spray drying method or a method in which a suitable adsorbent (e.g., silicic anhydride, starch, etc.) is added to a soft extract with a high extract concentration to obtain an adsorbed powder.

When an extract is used as Daisaikoto in the present invention, an extract prepared by the above-mentioned method may be used, or a commercially available product may be used. For example, as dried extract powder of Daisaikoto, Daisaikoto Dried Extract AM, Daisaikoto Dried Extract SN, and Daisaikoto Dried Extract Powder (all manufactured by Nippon Powder Co., Ltd.), as well as Daisaikoto Dried Extract F and Daisaikoto Dried Extract-F (all manufactured by Alps Pharmaceutical Co., Ltd.), are known as commercial products and can be obtained commercially.

In the appetite-regulating hormone secretion normalizing agent of the present invention, the content of Daisaikoto extract is not particularly limited as long as the effect of the present invention is exhibited, but is usually 5 to 100% by weight, preferably 10 to 90% by weight, more preferably 20 to 80% by weight, and even more preferably 30 to 60% by weight, calculated as the amount of dried extract powder of Daisaikoto extract. In the present invention, the amount of dried extract powder of Daisaikoto refers to the amount of the dried extract powder itself when a dried extract powder of Daisaikoto is used, and refers to the amount converted to the amount remaining after removing the solvent when a liquid extract of Daisaikoto is used. In addition, when the dried extract powder of Daisaikoto contains additives such as adsorbents added during production, the amount refers to the amount excluding the additives.

Other components The appetite-regulating hormone secretion normalizer of the present invention may be composed of Daisaikoto extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavorings, fragrances, powders, thickeners, dyes, and chelating agents. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the type of additives and bases used, the formulation form of the appetite-regulating hormone secretion normalizer, etc.

In addition, the appetite-regulating hormone secretion normalizing agent of the present invention may contain other nutritional components and pharmacological components as necessary, in addition to the Daisaikoto extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of components used, etc.

The dosage form of the appetite-regulating hormone secretion normalizing agent 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.

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 that are added as necessary, may be formulated according to the usual formulation methods used in the pharmaceutical field.

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, against symptoms caused by abnormal secretion of appetite-regulating hormones. An example of the appetite-regulating hormone is leptin.

More specifically, the appetite-regulating hormone secretion normalizer of the present invention can be used to reduce the amount of leptin in the blood to a normal level in cases of leptin resistance, which is characterized by excessive secretion of leptin in the blood.

Symptoms to which the appetite-regulating hormone secretion normalizer 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, becomes difficult to sense. Examples of reproductive dysfunction include disorders related to ovulation, pregnancy, and childbirth in women.

Dosage and Usage: The appetite-regulating hormone secretion normalizer of the present invention is administered orally. The dosage of the appetite-regulating hormone secretion normalizer of the present invention is appropriately set depending on the age, sex, constitution, etc. of the person to be administered, but for example, the amount is about 1 to 15 g per person per day in terms of the amount of dried extract powder of Daisaikoto extract, and may be administered 1 to 3 times a day, preferably 2 or 3 times a day. The timing of administration is not particularly limited, and may be either before meals, after meals, or between meals, but it is preferable to administer the agent before meals (30 minutes before meals) or between meals (2 hours after meals).

In order to more effectively normalize appetite-regulating hormone secretion, it is preferable to take the drug continuously for, for example, one week or more, preferably four weeks or more, and more preferably eight weeks or more.

2. Leptin resistance improving agent Daisaikoto can improve leptin resistance. Therefore, the present invention also provides a leptin resistance improving agent. As described above, symptoms caused by leptin resistance include obesity, sleep disorder, taste disorder, and reproductive dysfunction, so the leptin resistance improving agent of the present invention can be used to improve sleep disorder, taste disorder, and/or reproductive dysfunction.

The active ingredient, content, formulation, dosage, etc. of the leptin resistance improving agent are the same as those of "1. Appetite-regulating hormone secretion normalizing agent" above.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

Preparation of Daisaikoto Extract Powder The raw herbs used were 6.0 (weight parts, the same below), 4.0, 1.0, 3.0, 3.0, 3.0, 2.0, and 1.0, and after chopping, they were extracted with 20 times the weight (460 weight parts) of water 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.

Test Example: Female ddY mice were used, and were allowed to give birth at 10 weeks of age. 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 prepare leptin-resistant model mice. The leptin-resistant model mice were allowed to freely feed a high-fat diet not containing 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-parturient female ddY mice (normal mice) of the same age were also allowed to freely feed 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 DSK-free diet group was compared with the DSK 2% mixed diet group and the DSK 4% mixed diet group by Dunnett's method. The results are shown in Table 1.

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, but blood leptin levels were significantly reduced compared to the group fed a diet not containing DSK, and leptin resistance was improved.

Claims (1)

A leptin secretion normalizer that contains Daisaikoto extract .