WO2004098630A1 - Menopausal disorder inhibitor - Google Patents

Abstract

A menopausal disorder inhibitor comprising nucleoprotamine as an active ingredient; and a health food comprising the menopausal disorder inhibitor in an effective amount. Nucleoprotamine is a complex resulting from linkage with a nucleic acid of protamine being a basic protein contained in mature sperm nuclei of vertebrates, and can be obtained from, for example, albinos of fins such as salmon, trout, herring and pollack. Various discomforts and subjective symptoms attributed to menopausal disorder can be effectively inhibited by adequate intake of the above menopausal disorder inhibitor or health food at fixed intervals, for example, every day.

Description

 Specification

 Menopause inhibitor

 Technical field

 The present invention relates to a climacteric disorder inhibitor that can effectively suppress various unpleasant symptoms during menopause, that is, a so-called climacteric disorder, and a health food containing the effective amount thereof. .

 ^ Scenic technology

 [0002] From middle age to old age, aging of the body due to aging not only causes changes in the appearance of a person (loss of muscle strength, obesity, alopecia, increase in spots and wrinkles, etc.) and loss of mental strength, but also endocrine secretion. Often accompanied by system degradation or abnormalities. Decreases in hormones, such as female hormones (estrogens), cause so-called menopause in women. Menopause not only in women but also recently in men resulting from a decrease in the male hormone (testosterone) has also become an issue.

 [0003] Menopause is a serious problem, especially in women, and induces various symptoms as exemplified below.

 a) Menstrual abnormalities

 Shortening or prolonging the menstrual cycle, decreasing the number of menstrual cycles, irregular bleeding, etc.

 b) Changes in vascular response system

 Sudden heat such as hot flashes or hot flashes.

 c) mental symptoms

 Insomnia and depressive symptoms.

 d) Urogenital symptoms

 Frequent urination and urinary incontinence.

 e) Other

 Osteoporosis, hyperlipidemia, arteriosclerosis, etc.

[0004] As a typical treatment method for menopause in women, for example, hormone replacement therapy can be cited. Hormone replacement therapy is not available for menopausal women. This is a method of treating or suppressing menopausal disorders by replenishing strogen or progestogen) with a preparation in the form of an oral solution or patch. In addition, for example, Chinese medicine therapy is sometimes used.

 [0005] In addition to hormone replacement therapy and Kampo therapy, attempts have been made to suppress menopause by, for example, daily ingesting foods containing specific ingredients (so-called healthy foods) (for example, see Japanese Patent Application Laid-Open No. 069946 and JP-A-2003-113117). Foods useful for controlling menopausal disorders include, for example, foods containing isoflavones and bone proteins.

 Patent Document 1: Japanese Patent Application Laid-Open No. 2001-069946

 Patent Document 2: JP-A-2003-113117

 Disclosure of the invention

 Problems the invention is trying to solve

[0006] While the above hormone replacement therapy is effective in treating or suppressing menopause, there is a risk that various side effects (eg, an increased incidence of breast cancer, uterine cancer, etc.) may occur. In addition, hormone replacement therapy and Kampo therapy must be performed strictly based on the instructions of a specialist, and are not simple methods.

 Conventionally, even foods (or specific ingredients added to foods) that are considered to be effective in controlling climacteric disorders have specific effects on a wide variety of symptoms (syndromes) of menopause. It has not been proven and effective.

 Therefore, there has been a strong demand for a means of suppressing menopause that can be easily and safely implemented by anyone.

 [0007] The present invention has been made to solve the above-mentioned problems of the prior art, and it is an object of the present invention to be able to easily ingest it orally and take it regularly (for example, daily). Accordingly, an object of the present invention is to provide a menopausal disorder inhibitor that can effectively suppress menopausal disorders and a health food containing the effective amount thereof.

 Means for solving the problem

[0008] The present inventors have conducted intensive studies on the control of menopause, and as a result, have found that nucleoprotamine can effectively suppress menopause, and completed the present invention. The climacteric disorder inhibitor of the present invention is characterized by containing nucleoprotamine as an active ingredient.

 As the nucleoprotamine, nucleoprotamine obtained from milt of fish can be used.

 Said fish may be salmon, trout, herring or 鳕.

 The health food of the present invention is characterized by containing an effective amount of the present climacteric disorder inhibitor. The invention's effect

 [0009] The climacteric disorder inhibitor of the present invention can be easily orally ingested and, by taking an appropriate amount without side effects, can effectively suppress a wide range of climacteric disorders. In addition, the health food of the present invention contains an effective amount of the present menopausal inhibitor, and can be appropriately selected from various forms such as solid, liquid, jelly, and paste. It is suitable for daily intake.

 Embodiment of the Invention

 [0010] Nucleoprotamine, which is an active ingredient of the climacteric disorder inhibitor of the present invention, is a complex in which protamine, which is a basic protein present in mature sperm nuclei of vertebrates, binds to nucleic acids to form a complex. , Form sperm chromatin.

 Protamine has a low molecular weight (usually less than 10,000), and most of the constituent amino acids are basic amino acids, especially arginine. Nitrogen derived from arginine is equivalent to 2590% of the total nitrogen content, and acidic amino acids are Usually not included.

 Arginine has a wide variety of physiological effects, and has a sedative effect, an endocrine stimulating effect, a maintenance effect on gastrointestinal functions, and the like.

[0011] Nucleoprotamine is abundant in fish, for example, milts such as salmon, trout, herring, and 鳕. For example, after removing skins, muscles, blood vessels, and the like from milt of fish, drying and extraction are performed. It can be produced by purification by a conventional method, and may be in various forms such as powder, granule, paste, and liquid.

 By taking nucleoprotamine, it is possible to take protamine and nucleic acid at the same time.

[0012] There are two types of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Saved. Fish milt contains abundant DNA containing four nucleotides, adenine (A), thymine (T), guanine (G) and cytosine (C). Nucleic acids have the effect of activating cells and preventing senescence.

[0013] The form of use of the climacteric disorder inhibitor of the present invention is not particularly limited, and examples thereof include powders, granules, tablets, capsules, jellies, pastes, and various forms of health foods (including health drinks). May be. The health drink may be, for example, an aqueous solution, a suspension, or the like. Nucleoprotamine can be used as it is as the climacteric disorder inhibitor of the present invention, and if desired, other active ingredients (eg, vitamins and the like) may be added in an appropriate amount.

 The content of nucleoprotamine in the climacteric disorder inhibitor of the present invention or the content of the climacteric disorder inhibitor in the health food of the present invention is appropriately selected as desired.

 The health food of the present invention may contain, besides the present menopause inhibitor, those that can be added to ordinary foods.

 [0014] The climacteric disorder inhibitor of the present invention preferably ingests an amount of, for example, 0.1 to 10 g, preferably 0.2 to 5 g per day, for example. The climacteric disorder inhibitor of the present invention may be ingested once to three times a day, but the dosage may be appropriately increased or decreased depending on age, body weight, symptoms of climacteric disorder and the like.

 Example

 [0015] The present invention will be described in more detail with reference to the following examples.

 1) Production of the menopause inhibitor of the present invention

 The climacteric disorder inhibitor of the present invention was produced from salmon milt by the following procedure.

 i: Pretreatment of salmon milt

 Salmon milt lOOOOg was taken, and blood was removed and washed with water. After draining, 300 mL of water was added, and the mixture was ground and stirred to obtain a suspension.

 ii: Powdering treatment

 The suspension was filtered to remove solids such as milt, and then spray-dried with a spray drier to obtain a powdery substance.

 iii: Cleaning and collection

The powdery substance is washed with ethanol to remove ethanol-soluble matter and moisture, and dried under reduced pressure. After drying, 180 g of the present climacteric disorder inhibitor was obtained as a powder.

 The thus obtained menopause inhibitor is a pale yellow powder containing nucleoprotamine as a main component, and its chemical and physical properties are as follows.

 Nucleic acid content: 25-50% by mass

 Protein content: 25-60% by mass

 Ash content: 5-15% by mass

 Ninhydrin reaction: positive

2) Evaluation means of the menopause inhibitor of the present invention

 The Kupperman Index was used to objectively assess the degree of menopause. Tatsu Perman index was calculated based on Table 1 below.

[table 1]

Table 1: Calculation table of the Kupperman index

<クッパーマン指数の計算 >

<Calculation of Kupperman index>

 Hereinafter, a method of calculating the Kupperman index will be described. For each of the 11 symptoms of the syndromes shown in Table 1, the severity of the symptoms (symptoms) is represented by a number from 0 to 3. The meaning of each number is as follows.

 3: strong

 2: Medium

 1: weak

0: None Each symptom belonging to the syndromes in Table 1 can be further subdivided into several types of symptoms. Taking the example of perceptual impairment-like symptoms as examples, the perceptual impairment-like symptoms can be divided into two types, a symptom of numbness in the limbs and a symptom of dull limbs. Then, for each of the symptom "numbness in the limbs" and the symptom "dullness in the limbs", the intensity of the symptom is represented by a number from 0 to 3. The Kupperman index of each symptom belonging to the syndromes in Table 1 is calculated by the following formula (I).

 Formula (I): Highest score of each type of symptom X evaluation factor

 Specifically, for example, if the intensity of the symptom “limb numbness” is 1 and the intensity of the symptom “feeling of the limbs is 0” is 0, the Kupperman index of “symptoms like paresthesia” is 1 (the highest score). X2 (evaluation factor) = 2.

<Determination of the degree of menopause based on the Kupperman index (total)>

 The sum of the Kupperman indexes (Kupperman index (total)) for each of the 11 symptoms shown in Table 1 is the Kupperman index for menopause. The degree of menopause is determined from the Kuppa-Man index (total) based on the following criteria.

 35 or more: severe

 21 to 34: Moderate

 16 days 20: mild

[0019] <Index of therapeutic effect on menopause: Calculation of menopause index>

 The menopause index was used as an index of the therapeutic effect of menopause. The menopause index is calculated by the following equation (II).

 Formula (Π): Kupperman index after treatment (total) / Kupperman index for all treatments (total)

 The therapeutic effect of menopause is determined from the menopause index based on the following criteria.

 0.3 or less: significant effect

 0.3 Review 0.7: Valid

 0.7 or more: Disabled

[0020] 3) Evaluation results of the climacteric disorder inhibitor of the present invention

A total of 25 women aged 52 to 68 years received the menopause inhibitor of the present invention lg / day, and 60 days later, the Kupperman Index of all the women was calculated. The results are shown in Table 2 below. Table 2: Evaluation results of the menopause inhibitor of the present invention (1)

 55-year-old woman 59-year-old woman 61-year-old woman 55-year-old woman 58-year-old woman 59-year-old woman 55-year-old Syndrome

顔が熱くなる 1 0 1 0 0 0 2 0 1 0 0 0 1 Before and after m After 後 After Before and after 後 After and after

The face gets hot 1 0 1 0 0 0 2 0 1 0 0 0 1

Easy to sweat 1 0 1 0 0 0 0 0 2 1 0 0 2 Vasomotor disorders Numbness of hips and limbs 0 0 0 0 0 0 0 0 0 0 0 0 0 Shortness of breath 0 0 0 0 1 1 0 0 2 0 0 0 0 Kupfferman index 4 0 4 0 4 4 8 0 8 4 0 0 8 Numbness of limbs 0 0 0 0 0 0 0 0 1 0 0 0 1 Symptoms of intellectual injury Damage of limbs 0 0 0 0 0 0 0 0 0 1 0 0 1 Kupperman index 0 0 0 0 0 0 0 0 2 2 0 0 2 I can't sleep well at night 0 0 0 0 0 0 0 0 0 0 1 0 2 Insomnia Arousal 0 0 0 0 0 0 0 0 2 2 2 0 2 Kupperman index 0 0 0 0 0 0 0 0 4 4 4 0 4 Excitable 0 0 0 0 0 0 1 0 0 0 1 0 2 Nervous 0 0 0 0 0 0 2 0 0 0 1 0 0 Kupfferman index 0 0 0 0 0 0 4 0 0 0 2 0 4 Immediately go well with boring 1 0 0 0 0 0 2 2 0 0 1 0 1 0 0 0 0 0 0 1 2 0 0 0 0 ¹ Kupperman index 1 0 0 0 0 0 2 2 0 0 1 0 Dizziness and nausea 0 0 0 0 1 0 0 0 1 0 0 0 dizziness

 Kupperman index 0 0 0 0 1 0 0 0 1 0 0 0 Easy to get tired 0 0 1 1 2 1 1 2 0 1 0 Overall fatigue

 Kupperman index 0 0 1 1 2 1 1 2 0 1 0 Pain and muscular pain Shoulder stiffness Back pain-Pain in limbs 3 1 1 1 2 1 1 2 1 2 0 0 Joints

 Kupperman index 3 1 1 1 2 1 1 2 1 2 0 0 Headache 0 0 0 0 1 0 0 0 0 1 0 0 Headache

 Kupperman index 0 0 0 0 1 0 0 0 0 1 0 0 Heart palpitations 0 0 0 0 0 0 1 0 1 1 0 0 1 Heart palpitations

 Kupperman's index 0 0 0 0 0 0 1 0 1 1 0 0 1 Skin JI feels like an ant 0 0 0 0 1 0 0 0 0 0 0 0 0

Kupperman index 0 0 0 0 1 0 0 0 0 0 0 0 0 Number of members 合計 Total 8 1 6 2 11 7 17 4 20 12 1 1 0 22

Table 3: Evaluation results of the menopause inhibitor of the present invention (2)

 56 storehouse female 53 years old woman 53 years old woman 52 years old woman 57 years old woman 64 years old woman 68 years old woman 55 years old woman 58 years old woman kind

 Before and after Before and after Before and after 刖 After Before and after Before and after 前 Before and after After m After the face gets hot 0 0 0 0 1 0 0 0 1 1 3 2 1 0 0 1 1 1 It is easy to sweat 0 0 0 0 2 2 0 1 0 0 1 1 Vasomotor disorders Numbness of hips and limbs 0 0 0 0 1 0 2 2 0 0 1 1 3 3 0 0 1 0

 Shortness of breath 0 0 0 0 1 0 0 0 0 0 3 3 1 1 0 0 0 0 Kupperman index 0 0 0 0 4 0 8 8 4 4 12 12 12 12 0 4 4 4 Hands and feet numb 0 0 0 0 1 0 2 2 0 0 1 1 3 0 1 1 1 0Symptoms of paresthesia-like limbs Sensation of limbs 0 0 0 0 0 0 0 0 1 0 0 2 1 2 0 0 0 1 0

 Kupperman index 0 0 0 0 2 0 4 4 0 0 4 2 6 0 2 2 2 0 I can't sleep well at night 1 1 0 0 0 0 1 0 0 0 1 1 0 0 0 1 1 0 Insomnia 1 1 0 0 2 1 0 0 0 0 3 2 1 1 0 0 1 0

 Kupperman index 2 2 0 0 4 2 2 0 0 0 6 4 2 2 0 2 2 0 Excitable 0 0 0 0 0 0 0 0 0 1 1 1 1 0 0 0 0 1 1 Nervous nervous 0 0 0 0 1 1 0 0 0 0 2 2 2 3 1 1 0 0

 Kupperman exponent 0 0 0 0 2 2 0 0 0 2 4 4 4 6 2 2 2 2 Immediately take care of boring 0 0 0 0 0 0 0 0 0 0 3 2 0 1 0 0 0 0 Many 0 0 0 0 1 0 0 0 0 0 2 1 0 0 0 0 0 0

 Kupperman index 0 0 0 0 1 0 0 0 0 0 3 2 0 1 0 0 0 0 Dizziness and nausea 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Vertigo Kupperman index 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0

 Easy to get tired 1 1 0 0 1 0 1 1 2 2 2 1 2 3 0 0 1 1 whole body fatigue

 Kupperman index 1 1 0 0 1 0 1 1 2 2 2 1 2 3 0 0 1 1

 2 2 2 2 2 2 3 3 1 0 2 1 Joint pain, muscle pain Shoulder stiffness-Back pain 'Pain in the limbs 2 2 2 1 1 2

 Kupperman index 2 2 2 2 1 1 2 2 2 2 2 2 3 3 1 0 2 1 Head ache 1 0 0 0 1 0 0 0 0 0 0 0 1 1 2 1 0 0 Head ache

 Kupperman index 1 0 0 0 1 0 0 0 0 0 0 0 1 1 2 1 0 0 Heart palpitations 0 0 0 0 1 0 0 0 0 0 2 2 1 0 0 0 0 0 Heart 九 九

 Kupperman exponent 0 0 0 0 1 0 0 0 0 0 2 2 1 0 0 0 0 0 Feels like ants wearing skin 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Ant running feeling

Kupperman exponent 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Tubbaman number Total 6 5 0 2 17 5 17 15 8 10 35 29 32 29 7 1 1 13 8

4) Examination of the evaluation results of the climacteric disorder inhibitor of the present invention

 From the figures in the Total column of the Kupperman index in Table 4, the menopause index for all 25 women was calculated. The results are as follows.

 Menopause index: 237/361 ^ 0.66 (valid)

That is, the menopause index is 0.66, which is in the range of 0.3 to 0.7. Treatment of climacteric disorders with a climacteric disorder inhibitor was determined to be effective.

 In addition, for each symptom belonging to the syndrome, an index calculated by the above formula (II) is shown below. These indices are a measure of the therapeutic effect for each symptom.

 Vasomotor disorders: 86/128 ^ 0.67

 Symptoms of paresthesia: 18/36 = 0.50

 Insomnia: 30/48 ^ 0.63

 Intermediate: 30/38 ^ 0.79

 Depressed: 9,15 = 0.60

 Dizziness: 2Z6 = 0.33

 General malaise: 16/25 ^ 0.64

 Joint pain · muscle pain: 36/48 = 0.75

 Headache: 5/10 = 0.50

 Palpitations: 3/8 0.38

 Ant running feeling: 1/3 0.33

 Although the therapeutic effect on each symptom varies, it can be seen that the climacteric disorder inhibitor of the present invention is useful for inhibiting a wide range of symptoms.

Claims

The scope of the claims  [1] A climacteric disorder inhibitor comprising nucleoprotamine as an active ingredient.  2. The climacteric disorder inhibitor according to claim 1, wherein the nucleoprotamine is nucleoprotamine obtained from milt of fish. 3. The climacteric disorder inhibitor according to claim 2, wherein the fish is salmon, trout, herring or 鳕.  [4] A health food comprising an effective amount of the climacteric disorder inhibitor according to claim 1.