HK1238170A1 - Hot flash-suppressing agent - Google Patents

Description

Hot flash inhibitor

Technical Field

The invention relates to a hot flash inhibitor

Background

Hot flashes (hot flashes) are one of the representative symptoms of climacteric disorders. At present, climacteric disorders such as hot flashes can be treated by administration of traditional Chinese medicines or hormone replacement therapy. However, since the administration of the traditional Chinese medicine is accompanied by a problem that the patient does not take the medicine according to the instructions of the doctor because of the unique taste of the traditional Chinese medicine. In addition, hormone supplementation therapy has a problem of side effects such as nausea and an increase in the risk of carcinogenesis.

Patent document 1 describes a hot flashes preventing and treating agent containing a non-peptide compound as an active ingredient. In addition, patent document 2 describes a hot flash suppressant containing various plant extracts as an active ingredient. However, there is a need for the development of a preventive and therapeutic agent for hot flashes, which is easy to administer to all patients and is safer and more effective.

Thus, patent document 3 describes that α -lactalbumin selectively inhibits cyclooxygenase 2(COX-2) and exhibits an anti-inflammatory analgesic effect (anti-inflammatory action) based on the selective inhibition of COX-2. However, patent document 3 does not describe an action other than the anti-inflammatory action which shows selective inhibition of COX-2 based on α -lactalbumin. In addition, patent document 4 describes that α -lactalbumin exhibits a prebiotic effect. However, patent document 4 does not describe any effect other than α -lactalbumin.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open No. 2008-195728

Patent document 2: international publication WO2012/133825

Patent document 3: international publication WO2008/140041

Patent document 4: international publication WO2002/060279

Disclosure of Invention

Problems to be solved by the invention

The problem of the present invention is to provide a hot flash suppressant which is easy to take by a patient and is safer and more effective.

Means for solving the problems

The present inventors have conducted intensive studies to solve the above problems, and as a result, have found that α -lactalbumin, which is a widely consumed milk protein, can exert a hot flash inhibitory effect, and have completed the present invention.

That is, the present invention includes the following.

[1] A hot flash inhibitor contains alpha-lactalbumin as effective component.

[2] The hot flash inhibitor according to the above [1], which is used for inhibiting hot flash symptoms of climacteric disorder.

[3] The hot flashes suppressing agent according to [1] or [2] above, which consists of a unit package containing an effective amount of alpha-lactalbumin.

[4] A climacteric disorder improving agent comprising the hot flashes suppressing agent of [1] or [2 ].

[5] The menopausal disorder improving agent according to the above [4], which comprises a unit package containing an effective amount of alpha-lactalbumin.

[6] A method of suppressing hot flashes, comprising: administering alpha-lactalbumin or the hot flash inhibitor of any one of [1] to [3] above to a subject.

[7] The method according to the above [6], wherein the subject has symptoms of climacteric disorder.

[8] A method for improving a menopausal disorder, comprising: the ameliorating agent for menopausal disorder according to the above [4] or [5] wherein the agent is administered to a subject.

[9] A food or beverage for suppressing hot flashes, comprising alpha-lactalbumin as an active ingredient or the hot flashes suppressor of any one of the above [1] to [3 ].

[10] A pharmaceutical agent for suppressing hot flashes, which comprises alpha-lactalbumin as an active ingredient or the hot flashes suppressing agent of any one of the above [1] to [3 ].

The present specification includes the disclosure of Japanese patent application No. 2015-078574, which is the basis of priority of the present application.

Effects of the invention

The hot flash symptom can be effectively inhibited by the invention.

Drawings

FIG. 1 is a graph showing the change of skin temperature over time in the tail root of a rat affected by the administration of alpha-lactalbumin (. alpha. -La). In the figure, white circles indicate the results of the normal group, white triangles indicate the results of the control group (water + yohimbine administration), and black circles indicate the results of the α -La administration group (α -lactalbumin + yohimbine administration). Statistical significance was indicated by p <0.05 and by p <0.01 relative to the control group.

FIG. 2 is a graph showing the change in skin temperature over time at the tail root of a rat affected by administration of celecoxib. In the figure, white circles indicate the results of the normal group, white triangles indicate the results of the control group (water + yohimbine administration), and black triangles indicate the results of the celecoxib administration group (celecoxib + yohimbine administration).

FIG. 3 is a graph showing the change with time of the skin temperature at the tail root of a rat affected by the administration of beta-lactoglobulin (. beta. -Lg). In the figure, white triangles indicate the results of the control group (water + yohimbine administration), and black squares indicate the results of the β -Lg administration group (β -lactoglobulin + yohimbine administration).

FIG. 4 is a graph showing the change of skin temperature over time at the tail root of a rat affected by administration of a Chinese medicinal preparation (Guizhi Fuling Wan). In the figure, white triangles show the results of the control group (water + yohimbine administration), and black diamonds show the results of the herbal preparation administration group (Guizhi Fuling Wan + yohimbine administration).

Detailed Description

The present invention will be described in detail below.

The invention relates to a hot flash inhibitor with alpha-lactalbumin as an effective component.

Alpha-lactalbumin, casein, beta-lactoglobulin, lactoferrin and the like are main components of proteins in milk of beasts (milk of mammals) such as milk. Alpha-lactalbumin is an acidic protein of about 14kDa and is contained in milk products and whey (whey) in high concentrations. The α -lactalbumin used in the present invention may be any α -lactalbumin derived from a mammal (human, bovine, sheep, goat, pig, etc.), preferably α -lactalbumin derived from bovine milk (cow milk) (bovine α -lactalbumin). The amino acid sequence of the bovine alpha-lactalbumin precursor is disclosed in accession numbers J05147 and AAA30367 by NCBI database, and in the full-length amino acid sequence (142 amino acids in length), 1 to 19 positions are signal peptides, and 20 to 142 positions are the amino acid sequence of mature protein. It is also known that a variant of bovine α -lactalbumin has a glutamine (Q) substituted for arginine (R) at position 29 of the amino acid sequence thereof (ミルク Gross dictionary, p.35 from the retail store). The alpha-lactalbumin secreted in milk is a mature form in which the signal peptide portion is cleaved from its precursor. In the present invention, alpha-lactalbumin generally refers to the mature form of alpha-lactalbumin which does not contain a signal peptide

Alpha-lactalbumin can be prepared from mammalian milk, especially veterinary milk and processed products thereof, by known techniques such as ammonium sulphate precipitation, ultrafiltration, ion exchange and the like. The content of alpha-lactalbumin in milk varies somewhat depending on the place of production, feed, etc., whereas the content of alpha-lactalbumin in milk produced in japan is usually about 1.2g/kg, and if milk is used as a raw material, a large amount of alpha-lactalbumin can be easily prepared. Alpha-lactalbumin can be chemically synthesized based on the amino acid sequence and base sequence, or can be produced by genetic engineering methods well known to those skilled in the art. Further, a commercially available α -lactalbumin (Sigma-Aldrich, Davisco, etc.) can be used as the α -lactalbumin.

As shown in examples described later, α -lactalbumin is effective in suppressing hot flashes and is useful as an active ingredient of a hot flash inhibitor.

In the present invention, "hot flashes" are symptoms of abnormal fever that occur in a chronic and repeated manner on the surface of the skin close to the face or the body. Here, "abnormal fever" means fever due to factors other than the following, such as an increase in ambient temperature, external factors such as use of a heating device, and transient factors such as fever, sunburn, sunstroke, exercise, mental stress accompanying infection and inflammation, or fever exceeding the normal level due to these transient factors. Hot flashes occur not only as one of typical symptoms of climacteric disorder but also as other disease symptoms accompanied by autonomic nervous system abnormalities, such as autonomic nervous system dysfunction, goiter, alcohol dependence, and diabetes.

The hot flash suppressing agent according to the present invention can suppress hot flashes associated with other disease symptoms accompanied by autonomic nervous system abnormalities, such as goiter, alcohol dependence, diabetes, and the like, and can suppress hot flashes associated with climacteric disorders in a subject to which α -lactalbumin contained therein is administered (ingested) in an effective amount. Thus, for example, the present invention also provides a method of suppressing hot flashes comprising: the hot flash suppressing agent of the present invention is administered to a subject in a dose equivalent to an effective amount of α -lactalbumin.

The hot flash inhibitor of the present invention can suppress hot flashes associated with other disease symptoms accompanied by autonomic nervous system abnormalities, such as goiter, alcohol dependence, and diabetes, and preferably can suppress hot flashes associated with climacteric symptoms.

In the present invention, "suppression" of hot flashes means improvement of hot flashes from a state in which hot flashes have already occurred and a state in which hot flashes are likely to occur (climacteric disorder, etc.), and includes reduction of the level of hot flashes and prevention of hot flashes.

As described in the examples below, the effect of suppressing hot flashes can be determined (evaluated) using the continuity of skin temperature as an index. For example, the hot flash suppression effect can be determined by measuring the degree of suppression of the increase in skin temperature at the tail root of the rat over time while comparing the state of administration of the test substance with the state of non-administration of the test substance (the state of administration of water instead of the test substance) using an ovariectomized rat to which yohimbine is administered (yohimbine administration model). Specifically, the yohimbine administration model was used to compare the state in which the test substance was administered (test substance-administered group) with the state in which the test substance was not administered (control group), and the average value of the rise range of the skin temperature from 10 minutes to 80 minutes after the administration of yohimbine was evaluated based on the skin temperature immediately before the administration of yohimbine. Then, in the test substance-administered group, the average value of the skin temperature rise ranges is 70% or less, preferably 65% or less, more preferably 60% or less, and still more preferably 55% or less, with respect to the control group, and it can be determined that the hot flashes are suppressed.

The hot flash suppressing agent of the present invention may be a composition containing other pharmacologically active components, in addition to α -lactalbumin.

The hot flashes suppressing agent of the present invention can be used for suppressing hot flashes, preferably hot flashes due to climacteric symptoms, independently of the inhibitory action of cyclooxygenase 2(COX-2) or anti-inflammatory action based thereon. Therefore, for example, the present invention also provides an agent for ameliorating menopausal disorders, which comprises the hot flashes inhibitor of the present invention. In this case, the agent for ameliorating menopausal disorders, which contains the hot flashes suppressing agent according to the present invention, may be a composition containing other pharmacologically active ingredients, in addition to the hot flashes suppressing agent having an effect of ameliorating menopausal disorders. The present invention also provides a method for improving a menopausal symptom, which comprises: the agent for improving a menopausal disorder is administered to a subject. In the present invention, the improvement of the climacteric disorder means the improvement, alleviation or disappearance of the climacteric disorder including hot flashes. The hot flash suppressant according to the present invention may also be used for reducing the risk of hot flashes, for example, hot flashes that are symptoms of climacteric disorders. Thus, the hot flashes suppressing agent of the present invention can be used as a component of a therapeutic or prophylactic agent for various diseases associated with hot flashes. The hot flashes suppressing agent of the present invention may be administered (ingested) parenterally, for example, enterally, or orally, preferably orally.

As the subject (subject) to which the hot flash suppressing agent of the present invention is administered, there may be mentioned: including any mammals (subjects) such as humans, domestic animals (horses, cows, sheep, goats, pigs, etc.), pets (dogs, cats, rabbits, etc.), experimental (test) animals (mice, rats, monkeys, etc.), and preferably, there are exemplified: mammals suffering from hot flashes, mammals with diseases and factors that are susceptible to hot flashes.

The dose or intake amount of the hot flashes suppressing agent of the present invention can be appropriately set in consideration of various factors such as the route of administration and age, weight, and symptoms of the subject, and preferably can be set in accordance with the dose or intake amount of α -lactalbumin, and for example, 30mg to 10g, preferably 50mg to 5g, and more preferably 100mg to 2g can be administered once or one meal. The hot flashes related to the invention may be administered in a single dose, or may be administered several times at intervals of several hours to several months.

The hot flash suppressing agent of the present invention is preferably packaged (composed of unit packages) in a unit dose (one-time intake amount) from the viewpoint of hygiene at the time of administration (ingestion) and ease of handling at the time of transportation and storage. Thus, for example, the present invention also provides a hot flash suppressant which consists of a unit package. In the present invention, the "unit package form" may be a unit dose package form of one administration or one meal. The unit dose of the hot flashes inhibitor according to the invention for one administration or one meal is, for example, 5g to 500g (or 5mL to 500mL), preferably 10g to 300g (or 10mL to 300mL), and more preferably 50g to 200g (or 50mL to 200 mL). The unit dose of the hot flash suppressant of the present invention may be a daily dose, or 1/2 to 1/10 daily doses obtained by dividing the daily dose into small portions.

The hot flash suppressing agent of the present invention may be incorporated (added) to a drug or a food or drink, or may be used in combination with a drug or a food or drink. Therefore, for example, the present invention also provides a pharmaceutical or food or beverage containing the hot flashes related to the invention, and a combination of the pharmaceutical or food or beverage with the hot flashes related to the invention. The drug or food or drink containing the hot flashes suppressing agent of the invention or the drug or food or drink combined with the hot flashes suppressing agent of the invention can be administered (ingested) to the subject for suppressing hot flashes.

The present invention also provides a pharmaceutical, a food or a drink containing α -lactalbumin as an active ingredient. The medicine and food and drink are preferably used for suppressing hot flashes. In a preferred embodiment, the drug, food, or drink of the present invention may be a drug, food, or drink for suppressing hot flashes associated with a climacteric disorder and for improving a climacteric disorder by suppressing the hot flashes. The drug and food and drink of the present invention can also be used for a drug and food and drink that reduces the risk of developing hot flashes, such as hot flashes that are symptoms of climacteric disorders.

The drug according to the present invention may further contain pharmaceutically acceptable adjuvants for pharmaceutical preparations (for example, inert carriers (solid and liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizing agents, suspending agents, coating agents, coloring agents, taste corrigents, preservatives, buffers, pH adjusters) and the like as other pharmacologically active components. Specifically, the drug according to the present invention may contain an artificial cell structure such as a ribosome, in addition to water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerol, propylene glycol, polyethylene glycol, vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, and the like. In this case, the formulation auxiliary agent and the like can be appropriately selected according to the formulation of the formulation. The drug of the present invention may contain appropriate amounts of vitamins, minerals, saccharides, amino acids, peptides, antibiotics, and the like.

The medicine can be prepared into any of the following dosage forms: solid preparations such as tablets, granules, powders, pills, capsules and the like; liquid preparations such as liquid preparations, suspensions, syrups and the like; gels, aerosols, and the like. When the drug is used as a liquid preparation, the drug may be reconstituted with, for example, physiological saline before use to prepare a desired dry product. The amount of the α -lactalbumin to be incorporated into the drug of the present invention may be appropriately set, and may be changed depending on the form of the drug, the adjuvant of the preparation, the severity of the target disease, and the like.

The food or drink of the present invention may further contain adjuvants (for example, inert carriers (solid and liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizing agents, suspending agents, coating agents, coloring agents, taste corrigents, preservatives, buffers, pH regulators) and the like which are acceptable in the production of food or drink. Specifically, the food or drink according to the present invention may further contain water, proteins, sugars, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, and the like.

In the present invention, examples of the raw material (raw material) of the protein include: examples of the protein include animal proteins such as whole milk powder, skim milk powder, partially skim milk powder, whole condensed skim milk, partially skim condensed skim milk, casein (α -casein, β -casein, and κ -casein), whey, desalted whey, whey powder, desalted whey powder, Whey Protein Concentrate (WPC), Whey Protein Isolate (WPI), β -lactoglobulin, lactoferrin, egg protein, and meat protein, plant proteins such as soybean protein, decomposed products thereof, peptides such as casein phosphopeptides, arginine, and lysine, and amino acids. In the present invention, examples of the sugar-containing raw material include: lactose, saccharides, modified starch (soluble starch, British starch, oxidized starch, starch esters, starch ethers, etc., in addition to dextrin), dietary fiber, etc. In the present invention, examples of the lipid material include: animal fat and oil such as butter, cream, phospholipid, lard, fish oil, fractionated oil thereof, hydrogenated oil, and interesterified oil; vegetable oils and fats such as palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, hydrogenated oils, and transesterified oils. These substances and components may be used alone or in combination of two or more. These substances and components may be synthetic products or natural products.

In the present invention, examples of the raw materials of vitamins include: non-protein nitrogen, sialic acid, vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, nicotinic acid, pantothenic acid, biotin, inositol, choline, folic acid, etc. In the present invention, examples of the mineral-based raw material include: whey minerals, calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, etc. In the present invention, examples of the organic acid raw material include: malic acid, citric acid, lactic acid, tartaric acid, erythorbic acid, and the like. These substances and components may be used alone or in combination of two or more. These substances and components may be synthetic products or natural products.

The food or drink according to the present invention may be in any form such as a dairy product, a processed food, a prepared dish, a snack, a seasoning, a beverage, or the like. The food or drink according to the present invention is preferably in the form of a functional food. The food or drink according to the present invention may be a supplement for humans, for example, in a state of having an onset of hot flashes or a state of being likely to have an onset of hot flashes (climacteric disorder or the like).

In the present invention, the "functional food" refers to a food that can impart a predetermined functionality to a living body, and includes, for example: specific health foods (including the contingent special care [ specific health food ]); health functional food including functional labeled food and nutritious functional food; food for special use; a nutritional supplement food; a health aid food; supplements (for example, supplements in various dosage forms such as tablets, coated tablets, sugar-coated tablets, capsules, and liquids); all health foods such as beauty foods (for example, diet foods). In addition, in the present invention, the "functional food" includes a Health food suitable for the Health emphasis statement (Health close) based on the CODEX (FAO/WHO joint food standards committee) food standard.

The food or drink of the present invention may be prepared in any form such as solid, liquid, mixture, suspension, paste, gel, powder, granule, capsule, etc. The food or drink according to the present invention may contain the hot flash suppressing agent or α -lactalbumin according to the present invention by any suitable method available to those skilled in the art. Specifically, the food or drink according to the present invention may be prepared in any form such as a capsule containing the moist heat inhibitor or α -lactalbumin, an edible film or an edible coating agent covering the moist heat inhibitor or α -lactalbumin, or a tablet containing the moist heat inhibitor or α -lactalbumin and (or with) a suitable excipient. The food or drink according to the present invention may be produced by processing a composition containing the hot flash inhibitor or α -lactalbumin according to the present invention and other food materials. The food or drink according to the present invention may be prepared by adding (adding) a moist heat inhibitor or α -lactalbumin to various foods (e.g., milk, a refreshing drink, fermented milk, yogurt, cheese, bread, cookies, salty cookies, pizza crusts, prepared milk powder, liquid foods, foods for patients, nutritional foods, frozen foods, processed foods, and other commercially available foods), or may be prepared by combining various foods with a moist heat inhibitor or α -lactalbumin. The pharmaceutical or food or drink of the present invention may contain the hot flash suppressing agent or α -lactalbumin of the present invention in a single administration or a single meal.

The subject to which the pharmaceutical or food or beverage of the present invention is administered (subject) may be the same as the subject to which the tidal fever inhibitor is administered (subject).

The present invention also includes the following items (1) to (6).

(1) A method for suppressing hot flashes (improving climacteric complaints), which comprises: and (d) a step of (orally) administering (allowing the subject to ingest) α -lactalbumin or a composition (agent) containing α -lactalbumin to the subject.

(2) Use of alpha-lactalbumin in the manufacture of a hot flash inhibitor.

(3) Alpha-lactalbumin for use in inhibiting hot flashes.

(4) A method of manufacturing a hot flash suppressing agent, comprising: and (3) compounding the alpha-lactalbumin and a pharmaceutically acceptable carrier.

(5) A composition (agent) containing alpha-lactalbumin, which is added into medicine (pharmaceutical composition) or food and drink (dietary composition) and is used for inhibiting hot flashes.

(6) A method for imparting a hot flashes suppressing effect to a pharmaceutical composition, nutraceutical composition, medicament, pharmaceutical agent, dietary composition, food or drink, nutritional composition, food for special use, nutritional functional food, health food, or the like, comprising: adding (blending) alpha-lactalbumin or a composition containing alpha-lactalbumin to a pharmaceutical composition, a nutraceutical composition, a drug, a medicament, a dietary composition, a food or drink, a nutritional composition, a food for special use, a nutritional functional food, a health food, or the like.

Examples

The present invention will be further specifically described below by way of examples. However, the technical scope of the present invention is not limited by these examples.

[ example 1]

Ovariectomized rats given yohimbine (yohimbine dosing model) were used as an animal model of hot flashes. Therefore, this example investigated the effect of α -lactalbumin (α -La) on the inhibition of skin temperature rise (hot flashes) using a yohimbine dosing model.

Ovaries of 7-week-old female SD rats (SLC, Japan) were removed to prepare climacteric disorder model animals, and the animals were used in the experiment after one week. In this experiment, rats were equally divided into 3 groups (each group: n-6) by average body weight.

For the normal group and the control group, distilled water for injection was orally administered in an amount of 10mL/kg body weight; for the α -La-administered group, α -La was orally administered in an amount of 300mg/kg body weight (α -La in distilled water solution for injection was orally administered in an amount of 10mL/kg body weight).

After 30 minutes from the oral administration, distilled water for injection was subcutaneously injected in an amount of 2mL/kg body weight in the normal group; for the control group and the α -La administration group, yohimbine was subcutaneously administered in an amount of 2mg/kg body weight (a distilled water solution for injection to which yohimbine was subcutaneously administered in an amount of 2mL/kg body weight). Further, the skin temperature of the rat tail root was measured every 5 minutes with the passage of time from the time the subcutaneous injection was administered to 80 minutes later.

The changes in skin temperature over time in the root of the tail of the rat are shown in table 1. The skin temperature of the normal group hardly rose. The skin temperature of the control group increased with time due to the action of yohimbine. In contrast, the α -La administered group showed a suppression of yohimbine action and a significant suppression of skin temperature increase, as compared with the control group.

The results show that the skin temperature rise (hot flashes) can be suppressed by the action of α -La.

[ example 2]

Inhibition of cyclooxygenase 2(COX-2) is known as one of the mechanisms of action of the anti-inflammatory effect of alpha-lactalbumin (. alpha. -La). Therefore, in this example, the inhibitory effect of COX-2 inhibition on skin temperature rise (hot flashes) was investigated using a yohimbine administration model. Herein, Celecoxib (Celecoxib) is used as a selective COX-2 inhibitor.

Ovaries of 7-week-old female SD rats (SLC, Japan) were removed to prepare climacteric disorder model animals, and the animals were used in the experiment after one week. In this experiment, rats were equally divided into 3 groups (each group: n-6) by average body weight.

For the normal group and the control group, the gum arabic solution (1 wt%) was orally administered in an amount of 10mL/kg body weight; for the celecoxib administration group, celecoxib was orally administered in an amount of 10mg/kg body weight (a dispersion of celecoxib in gum arabic solution (1 wt%) was orally administered in an amount of 10mL/kg body weight). Here, in order to improve the dispersibility of celecoxib, a gum arabic solution is used.

After 30 minutes from the oral administration, distilled water for injection was subcutaneously injected in an amount of 2mL/kg body weight in the normal group; for the control group and the α -La administration group, yohimbine was subcutaneously administered in an amount of 2mg/kg body weight (a distilled water solution for injection to which yohimbine was subcutaneously administered in an amount of 2mL/kg body weight). Further, the skin temperature of the rat tail root was measured every 5 minutes with the passage of time from the time the subcutaneous injection was administered to 80 minutes later.

The changes in skin temperature over time in the root of the tail of the rat are shown in Table 2. The skin temperature of the normal group hardly rose. The skin temperature of the control group increased with time due to the action of yohimbine. In addition, the effect of yohimbine was not inhibited in the celecoxib-administered group compared with the control group, and the skin temperature was increased with the passage of time.

The results show that inhibition of the cyclooxygenase 2(COX-2) enzyme of celecoxib does not inhibit the rise in skin temperature (hot flashes). Namely, the following results are shown: the COX-2 inhibitory effect of alpha-La, which brings an anti-inflammatory effect, cannot inhibit the increase in skin temperature (hot flashes), and the mechanism of action of the COX-2 inhibitory effect of alpha-La on the increase in skin temperature (hot flashes) is different from that of COX-2 inhibition.

[ example 3]

Beta-lactoglobulin (. beta. -Lg) is a representative whey protein (milk protein) other than alpha-lactalbumin (. alpha. -La). Therefore, this example investigated the effect of β -lactoglobulin (β -Lg) on the inhibition of the rise in skin temperature (hot flashes) using a yohimbine administration model.

Ovaries of 7-week-old female SD rats (SLC, Japan) were removed to prepare climacteric disorder model animals, and the animals were used in the experiment after one week. In this experiment, rats were equally divided into 2 groups (each group: n-4) by average body weight.

For the control group, distilled water for injection was orally administered in an amount of 10mL/kg body weight; in the β -Lg administration group, β -Lg was orally administered in an amount of 300mg/kg body weight (β -Lg in distilled water for injection was orally administered in an amount of 10mL/kg body weight).

After 30 minutes had elapsed since the oral administration, yohimbine (a distilled water solution for injection to which yohimbine was administered by subcutaneous injection in an amount of 2mg/kg body weight) was administered to the control group and the β -Lg administration group by subcutaneous injection in an amount of 2mL/kg body weight. Further, the skin temperature of the rat tail root was measured every 5 minutes with the passage of time from the time the subcutaneous injection was administered to 80 minutes later.

The changes in skin temperature over time in the tail root of the rat are shown in table 3. The skin temperature of the control group increased with time due to the action of yohimbine. In addition, the β -Lg-administered group had no effect of yohimbine inhibition, as compared with the control group, and the skin temperature increased with time.

The results show that whey proteins other than α -La, such as β -Lg, do not inhibit the increase in skin temperature (hot flashes). Namely, the following results are shown: the inhibitory effect of skin temperature rise (hot flashes) is not visible in all milk proteins, but is specifically visible in α -La.

[ example 4]

The cassia twig and tuckahoe pill is a typical traditional Chinese medicine preparation suitable for improving climacteric disturbance. Therefore, in this example, the inhibitory effect of Guizhi Fuling Wan on skin temperature rise (hot flashes) was studied using a yohimbine administration model.

Ovaries of 7-week-old female SD rats (SLC, Japan) were removed to prepare climacteric disorder model animals, and the animals were used in the experiment after one week. In this experiment, the rats were equally divided into 2 groups (each group: n-5) by average body weight.

For the control group, distilled water for injection was orally administered in an amount of 10mL/kg body weight; for the group to which the Chinese medicinal preparation was administered, Guizhi Fuling pills (distilled water solution for injection to which Guizhi Fuling pills were orally administered in an amount of 10mL/kg body weight) were orally administered in an amount of 1g/kg body weight.

After 30 minutes had elapsed since the oral administration, yohimbine (a distilled aqueous solution for injection to which yohimbine was administered by subcutaneous injection in an amount of 2mg/kg body weight) was administered to the control group and the group to which the Chinese medicinal preparation was administered by subcutaneous injection in an amount of 2mL/kg body weight. Further, the skin temperature of the rat tail root was measured every 5 minutes with the passage of time from the time the subcutaneous injection was administered to 80 minutes later.

The changes with time of the skin temperature at the tail root of the rat are shown in table 4. The skin temperature of the control group increased with time due to the action of yohimbine. In addition, compared with the control group, the effect of yohimbine in the group to which the Chinese medicinal preparation was administered was not inhibited, and the skin temperature was increased with the lapse of time.

The results show that the traditional Chinese medicine preparation such as Guizhi Fuling pill which is suitable for improving climacteric disturbance can not inhibit the rise of skin temperature (hot flash). This indicates that: the effect of suppressing the rise in skin temperature (hot flashes) is observed with a single administration of α -La, whereas the effect of suppressing hot flashes is not observed with a single administration of a traditional Chinese medicine preparation, and even a preparation for improving climacteric symptoms is not always effective for suppressing hot flashes.

Industrial applicability

The present invention can be used for producing foods, drinks and medicines useful for ameliorating hot flashes, and particularly can be used for producing foods, drinks and medicines useful for ameliorating hot flashes caused by climacteric disorders.

All publications, patents and patent applications cited in this specification are herein incorporated by reference as if fully set forth.

Claims (7)

1. A hot flash inhibitor contains alpha-lactalbumin as effective component.

2. The hot flash inhibitor according to claim 1, which is used for inhibiting hot flash symptoms of climacteric disorder.

3. The hot flash suppressant according to claim 1 or 2, consisting of a unit package containing an effective amount of α -lactalbumin.

4. An ameliorating agent for menopausal disorder, which comprises the hot flash inhibitor according to claim 1 or 2.

5. An improver for menopausal disorder according to claim 4, which consists of a unit package form containing an effective amount of α -lactalbumin.

6. A food or drink for suppressing hot flashes, comprising alpha-lactalbumin as an active ingredient or the hot flashes suppressing agent according to any one of claims 1 to 3.

7. A medicament for suppressing hot flashes, comprising alpha-lactalbumin as an active ingredient or the hot flashes suppressing agent as claimed in any one of claims 1 to 3.