JP6940864B2 - Testicular disorders preventive and / or improver - Google Patents

Description

The present invention relates to a testicular disorder preventive and / or ameliorating agent. More specifically, the present invention relates to pharmaceuticals, foods and drinks, feeds containing the testicular disorder preventive and / or ameliorating agent, and methods for improving testicular disorders in animals.

In recent years, it is said that one in six to seven couples has infertility in Japan due to the aging of childbirth plans, decrease in sperm count, stress, and the like. Therefore, there is a social problem that the declining birthrate is accelerating.
As a countermeasure, assisted reproductive technology is provided. The number of artificial insemination, in vitro fertilization, and intracytoplasmic sperm injection has increased rapidly year by year, and now nearly 400,000 cases are performed annually. The cost of artificial insemination is about 300,000-400,000 yen at a time. However, it is rare to succeed once, and the financial burden on the household is large. Above all, the physical and mental burden on women is great.

However, the cause of infertility comes from half men and women. Therefore, it is necessary to approach male infertility.
About 90% of male infertility is due to sperm dysfunction. The causes of male infertility are said to be the onset of varicocele and testicular inflammation, elevated testicular temperature, and impaired blood flow. However, considering the recent decrease in sperm count worldwide, various stresses that are converted into oxidative stress in the body are also expected to be a factor.

One of the important things in male infertility is the number and condition of sperm. Sperm grow from primordial germ cells in the order of spermatogonia, spermatocytes, and spermatocytes to become mature sperms. When stress such as heat is applied in the process of this growth, spermatogenesis is affected, spermatogenesis does not go well, the number of sperms decreases, and the ability is inferior.
In addition, mature sperms are stored in the epididymis and tail, and even if various stresses including heat stress are applied to the testes, the sperm's motility and fertilization ability are reduced.

Infertility is not only a problem for humans, but also for animals such as livestock. Livestock infertility is caused by summer temperature rise (global warming), livestock eutrophication, stress, and the like.
In particular, heat stress caused by high temperature and high humidity in summer reduces the fertility of livestock. This is called summer infertility. Along with the decline in fertility due to perinatal diseases, it has become a serious problem in the livestock industry.

Infertility of livestock will lead to a further decrease in food (protein source) self-sufficiency rate. Therefore, in vitro fertilization is also performed in livestock, but its effectiveness is said to be low in summer.

Therefore, in order to improve the above situation, various measures against infertility of males such as males or domestic animals have been studied.
For example, an edible plant-derived sperm function improving agent has been developed (Patent Document 1). The sperm function improving agent is contained as an active ingredient of xanthangelol and 4-hydroxydelicin contained in the Angelica keiskei extract.
The sperm function improving agent may be added to foods and feeds and can be orally administered. Therefore, infertile men and livestock can be easily ingested.

JP-A-2016-333131

An object of the present invention is to provide a testicular disorder preventive and / or ameliorating agent for preventing / ameliorating infertility caused by males or males.

As a result of diligent studies to solve the above problems, the present inventors have found that a compound having a hydroxytyrosol skeleton or a tyrosol skeleton is effective in improving testicular disorders, and completed the present invention.

Therefore, the present invention provides a testicular disorder preventive and / or ameliorating agent containing a hydroxytyrosol skeleton or a compound having a tyrosol skeleton as an active ingredient.
In the present invention, the compound having a hydroxytyrosol skeleton or a tyrosol skeleton is, for example, oleuropein, an oleuropein derivative or hydroxytyrosol. These are contained in olives, for example.
In addition, the present invention also contains a hydroxytyrosol skeleton or a compound having a tyrosol skeleton as an active ingredient, a drug for preventing and / or improving testis disorder, a food or drink for preventing and / or improving testis disorder, and a testis disorder prevention and /. Alternatively, a feed for improvement is also provided.
Furthermore, the present invention also provides a method for preventing and / or ameliorating testicular disorders, which comprises administering a hydroxytyrosol skeleton or a compound having a tyrosol skeleton to a male animal. Animals may or may not include humans.
Furthermore, the present invention uses a hydroxytyrosol skeleton or a compound having a tyrosol skeleton in the production of an agent for preventing and / or ameliorating testicular disorders, and a hydroxytyrosol skeleton or tyrosol used for preventing and / or ameliorating testicular disorders. It can also be expressed as a compound having a skeleton.

The testicular disorder includes, for example, a disorder in which the sperm production ability is reduced for some reason and the number and quality of sperms are lowered, or a disorder in which the number of mature sperms is reduced for some reason or the motor function is lowered. nothing.

INDUSTRIAL APPLICABILITY According to the present invention, a novel male or male infertility treatment agent having an effect of improving testicular disorders can be provided. Since the active ingredient contained in the agent may be derived from, for example, an olive extract, it is highly possible that the active ingredient has few side effects and is excellent in safety.

It is a graph which shows the sperm concentration of the mouse which administered or did not administer oleuropein. It is a graph which shows the sperm motility rate of the mouse which administered or did not administer oleuropein. It is a graph which shows the motile sperm concentration of the mouse which administered or did not administer oleuropein. It is a graph which shows the linear velocity of the sperm of the mouse which administered or did not administer oleuropein. It is a graph which shows the curve velocity of the sperm of the mouse which treated or did not administer oleuropein. It is a graph which shows the average rate of the sperm of the mouse which treated or did not administer oleuropein. It is a graph which shows the head amplitude of the sperm of the mouse which administered or did not administer oleuropein. It is a graph which shows the testis weight ratio of the mouse which administered or did not administer oleuropein. It is a graph which shows the sperm concentration of the mouse which administered or did not administer oleuropein. It is a graph which shows the sperm motility rate of the mouse which administered or did not administer oleuropein. It is a graph which shows the motile sperm concentration of the mouse which administered or did not administer oleuropein.

<1. Testicular disorders preventive and / or improver>
The active ingredient of the testicular disorder preventive and / or ameliorating agent of the present invention is a compound having a hydroxytyrosol skeleton or a tyrosol skeleton. Hydroxytyrosol and tyrosol are phenolic antioxidants found in various natural products.
The hydroxytyrosol skeleton is represented by the following structural formula (I).

The tyrosol skeleton is represented by the following structural formula (II).

Examples of the compound having a hydroxytyrosol skeleton or a tyrosol skeleton include, but are not limited to, oleuropein, an oleuropein derivative, and hydroxytyrosol. In the present invention, the above compounds may be used alone or in combination of two or more.
Oleuropein has the structure of formula (III) below.

In the present invention, the oleuropein derivative means a compound capable of exerting an effect of improving testicular disorders equivalent to the compound having the hydroxytyrosol skeleton of the structural formula (I) or the tyrosol skeleton of the structural formula (II) in vivo. .. Specifically, it is a compound that can be produced from oleuropein by an in vivo reaction such as oxidation / reduction, hydrolysis / dehydration, methylation / demethylation, esterification, and decarboxylation.

Specific examples of the oleuropein derivative include oleuropein aglycon represented by the following structural formula (IV), demethylated oleuropein aglycon represented by the following structural formula (V), oleuropein aglycon represented by the following structural formula (VI), and the following. Examples thereof include a dialdehyde-type oleuropein aglycon represented by the structural formula (VII) and a diacet-type oleuropein aglycon derivative represented by the following structural formula (VIII). Oleuropein aglycone is a compound in which glucose is removed from oleuropein.

Hydroxytyrosol skeletons or compounds having a tyrosol skeleton, oleuropein, oleuropein derivatives and hydroxytyrosol are contained in natural olives, enju, ibota and the like. These can be used in the present invention as raw materials, natural products as they are, processed products by drying, freezing, heating, crushing, pressing, extraction, etc., purified products of extracts, or derived products thereof. Of course, it is also possible to use chemically synthesized oleuropein or the like.

When a compound having a hydroxytyrosol skeleton or a tyrosol skeleton or the like is obtained from a natural product extract, extraction from olive (Olea europaea) is particularly preferable. Olive is an evergreen tree native to the Mediterranean Sea, and the olive oil obtained from its fruits has been edible for a long time. Regarding olive oil, it is widely known that its component, oleic acid, has an effect of lowering the amount of LDL cholesterol.

It is already known that olives contain a large amount of oleuropein and the like suitable for the present invention, and an extract containing oleuropein and the like can be obtained from olives by using an organic solvent such as water or alcohol or oil. As the organic solvent for olive extraction, methanol, ethanol, propanol, butanol, propylene glycol, 1,3-butylene glycol, glycerin, acetone, methyl ethyl ketone, ethyl acetate, ethers, chloroform, dichloromethane and the like can be used. .. Further, if the obtained extract is concentrated by a known method, oleuropein or the like can be obtained as a purified product.

For olives, any part of the fruit, leaves, flowers, stems and roots can be used, and these may be used in a raw state, or dried products, crushed products and the like may be used. Since olive contains a strong astringent component, it may be used as a raw material of this agent after being subjected to a well-known alkaline treatment with caustic soda or the like.

In particular, since olive leaves contain a large amount of oleuropein and the like, oleuropein and the like can be extracted by effectively utilizing the pruned and felled olive leaves. Olive leaves contain 5-20% oleuropein by dry weight. Further, when olive oil is squeezed from olive fruits, a large amount of plant water, treated water and squeezed residue are generated, and oleuropein and the like can be extracted from these. Further, since oleuropein and the like are also contained in olive oil, it may be extracted from olive oil or, in some cases, olive oil itself may be used.

As mentioned above, olive oil has been edible for a long time, which indicates the high safety of olive extract. Therefore, the testicular disorder preventive and / or ameliorating agent of the present invention containing oleuropein derived from olive extract as an active ingredient, and pharmaceuticals, foods and drinks, and feeds containing the same have the following advantages.

That is, since it is a component derived from a natural product, it is highly possible that health supplement foods and drinks (functional foods and drinks) such as pharmaceuticals and supplements can be continuously applied for a long period of time, and there is a high possibility that side effects are few. In addition, when applied to feed for industrial animals, it may be possible to prevent the occurrence of testicular disorders caused by stress due to poor management of the breeding environment and heat stress.

<2. Pharmaceuticals>
The pharmaceutical product of the present invention can be used orally as, for example, sugar-coated tablets, capsules, elixirs, microcapsules, granules, etc., or with water or other pharmaceutically acceptable liquids. Can be used parenterally in the form of injectables such as sterile solutions or suspensions. The dosage form of the pharmaceutical product of the present invention is not particularly limited, but an oral preparation is preferable from the viewpoint of ease of administration.

The pharmaceutical product of the present invention is a generally accepted preparation of the testicular disorder preventive and / or ameliorating agent of the present invention together with physiologically recognized carriers, flavoring agents, excipients, vehicles, preservatives, stabilizers, binders and the like. Manufactured by mixing in the unit dose form required for practice. Additives that can be mixed with tablets, capsules, etc. include, for example, binders such as gelatin, cornstarch, tragant, gum arabic, excipients such as crystalline cellulose, cornstarch, gelatin, alginic acid and the like. A swelling agent, a lubricant such as magnesium stearate, a sweetener such as sucrose, lactose or saccharin, a flavoring agent such as peppermint, red mono oil or cherry is used.

In addition to the testicular disorder preventive and / or ameliorating agents, the pharmaceutical products of the present invention further include other components that are effective for animals (including humans), such as polyphenols, proteins, amino acids, steroids, and vitamins. Kinds, sugars, lipids, minerals, hormonal agents, antibiotics, pigments and the like may be blended. Specific examples thereof include astaxanthin, coenzyme Q10, vitamin E, vitamin C, vitamin A, potassium chloride, calcium gluconate, sodium saccharin and the like.

The amount of the testicular disorder preventive and / or ameliorating agent to be added to the pharmaceutical product of the present invention is not particularly limited as long as the effect of the present invention is not impaired. In addition, the blending amount may change depending on the dosage form.
The amount to be blended in the pharmaceutical product is, for example, olive or its extract (in terms of dried product), usually 1 to 95% by mass, more preferably 5 to 90% by mass, and particularly preferably 10 to 50% by mass.

The dose of the drug of the present invention is not particularly limited as long as the effects of the present invention are not impaired, and the type of dosage form, administration method, age, body weight, symptoms, etc. of the administration target (human, animal) are taken into consideration. It can be changed as appropriate.
The daily dose at which the subject to be administered obtains the desired effect is preferably, for example, 5 to 6000 mg / 60 kg body weight per day as olive or its extract (dry matter equivalent), and further 10 to 3000 mg / day. It is preferably 60 kg body weight, particularly 20 to 1000 mg / 60 kg body weight, and most preferably 30 to 200 mg / 60 kg body weight.

<3. Food and drink>
The food and drink of the present invention can be in the form of, for example, a beverage, a powder, a powdered beverage, a tablet, a supplement, a jelly, a hard capsule or a soft capsule, and the shape is suitable for oral ingestion.

The food and drink of the present invention contains glucose, fructose, sucrose, maltose, sorbitol, stebioside, rubusoside, corn syrup, lactose, citric acid, tartrate acid, malic acid, succinic acid, and lactic acid in addition to the above-mentioned testicular disorder preventive and / or ameliorating agents. , L-ascorbic acid, dl-α-tocopherol, sodium erythorbinate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, Arabic gum, carrageenan, casein , Gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts and other minerals, and various other nutrients, pigments, fragrances, preservatives, etc., which are usually used as raw materials for food and drink. It can be produced by appropriately blending the above-mentioned substances. It may also be mixed with rice, wheat, corn, potatoes, sweet potatoes, soybeans, kelp, wakame seaweed, gelidiaceae, etc., which are generally used as food and drink materials.

The amount of the testicular disorder prevention and / or ameliorating agent to be added to the food or drink of the present invention is not particularly limited, but is usually 0.001 to 10% by mass, and more, in the case of olive or its extract (dry matter equivalent, the same applies hereinafter). It is preferably 0.01 to 5% by mass, particularly 0.1 to 1% by mass.
For example, in the case of a beverage, the amount of olive or its extract in the beverage is 0.001 to 0.5% by mass, further 0.005 to 0.25% by mass, particularly 0.02 to 0.15% by mass. Is preferable.
In the case of supplements such as capsules and tablets, those containing 1 to 95% by mass, more 5 to 90% by mass, and particularly 10 to 50% by mass of olive or its extract are preferable.

Examples of foods and drinks include health foods, functional foods, foods for specified health uses, nutritional supplements, enteral nutritional foods, and the like. In addition, these foods and drinks can also be fed to animals.

<4. Feed>
The feed of the present invention can be obtained by mixing the above-mentioned fertility therapeutic agent with raw grass, hay, green-cut feed crops (green-cut corn, etc.), straws, and the like.

Generally, livestock feed is roughly classified into three types: roughage, concentrated feed, and special feed. Of these, roughage refers to feed that has a relatively high crude fiber content and a small amount of digestible nutrients for its large volume. Raw grass, hay, green-cut forage crops (green-cut corn, etc.), root vegetables, straws, etc. are used as the roughage. In addition, concentrated feed refers to feed having a relatively high nutrient content and a low water content and crude fiber content. Concentrated feed includes cereals such as corn, mylo, barley, embaku, rice, millet, barnyard millet, millet, and kolyan, grain by-products (bran) such as rice bran and bran, peanut cake, cottonseed meal, and sunflower cake. Oil cakes such as rapeseed meal, sesame meal, and flaxseed meal are used.

The feed of the present invention can also be produced by adding olive fruits, flowers, stems, roots, preferably leaves to these feeds in a raw state or as a dried product. Olive leaves and the like can be added as they are or crushed into powder. It is also possible to add pomace generated during the squeezing of olive oil.

The amount and dose of the testicular disorder prevention and / or ameliorating agent to be added to the feed of the present invention can be determined according to the above-mentioned pharmaceutical products and foods and drinks.

<5. How to Prevent and / or Ameliorate Testicular Disorders>
Testicular disorders can be prevented and / or ameliorated by administering a hydroxytyrosol skeleton or a compound having a tyrosol skeleton to males or males of non-human animals.
Specifically, the above-mentioned drug, food and drink, and feed may be ingested by the administration target at the above-mentioned dose.
Although it depends on the administration subject, symptoms, etc., the administration period is preferably continuous administration, for example, for about 1 week to 1 year.

In addition, while administering the testicular disorder preventing and / or improving agent of the present invention, it is also possible to take an antioxidant, review the eating habits, review the lifestyle such as smoking, and the like.

Hereinafter, the present invention will be described in more detail based on Examples. It should be noted that the examples described below show an example of a typical example of the present invention, and the scope of the present invention is not narrowly interpreted by this.

In the following experiments, the effect was examined using oleuropein as an example of a compound having a hydroxytyrosol skeleton or a tyrosol skeleton, but the present invention is not limited to oleuropein.
In addition, mice were used as experimental animals, and the cause of infertility was determined to be due to serious heat stress in livestock.

<6. Examination of preventive and ameliorating effects of oleuropein on mature sperm disorders>
[1] Administration of oleuropein to mice and heat stress load Mature male mice,
It was divided into three groups: (1) room temperature treatment (room temperature treatment), oleuropein non-administration (2) hot heat treatment (42 ° C), oleuropein non-administration (3) hot heat treatment (42 ° C), and oleuropein administration.
Oleuropein (Extrasynthese (France), Cat.No.SSX0204) was orally administered daily (5 mg / kg / day) 5 days before the heat treatment.
The heat treatment was performed by exposing the posterior 1/2 including the testis and epididymis tail of the mouse to a constant temperature bath at 42 ° C. for 20 minutes. For room temperature treatment (control), the mice were allowed to stand at room temperature without being placed in a constant temperature bath. Environmental conditions other than temperature (lighting, ventilation, feeding method, etc.) were the same in both groups.
Twenty-four hours after heat treatment and room temperature treatment, mature sperms present in the epididymal tail were collected and analyzed as follows.

[2] Measurement of sperm concentration Buffer (2.2 mM HEPES, 1.2 mM MgCl ₂ , 100 mM NaCl, 4.7 mM KCl, 1 mM Pyruvic acid, 4.8 mM) for sperm placed on a heating plate at 37 ° C. It was cultured in Lactic acid hemi calcium salt, 5.5 mM D-Glucose, 20 mM Sodium bicarbonate, pH 7.35), and the sperm culture solution was collected after 15 minutes.
The sperm culture solution was centrifuged (conditions: 100 g, 1 min), and the sperm in the supernatant was measured. A sperm motility analyzer SMAS (Sperm Motility Analysis System) (Detect, Inc. (Japan)) was used to measure sperm concentration. More than 200 sperms were measured per sample, and the average value was used as the result.

(result)
The measurement result of sperm concentration is shown in FIG.
Compared with the control (room temperature treatment), the sperm concentration was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the sperm concentration in the hot heat-treated / oleuropein-administered group, which had been administered with oleuropein from 5 days before the hot-heat treatment, was equivalent to that of the control, and the sperm concentration was significantly higher than that in the hot-heat-treated / oleuropein-non-administered group. From this, it was clarified that oleuropein can suppress the decrease of mature sperm due to heat stress and prevent or improve the mature sperm disorder.

[3] Measurement of sperm motility rate The sperm motility rate was measured using a sperm motility analysis system SMAS (Sperm Motility Analysis System) (Detect Co., Ltd. (Japan)) according to the operating procedure of the system.

(result)
The measurement results of sperm motility are shown in FIG.
Compared with the control (room temperature treatment), the sperm motility was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the hot heat-treated / oleuropein-administered group had a sperm motility equal to or higher than that of the control, and the sperm motility was significantly higher than that of the hot-heated / oleuropein-non-administered group. From this, it was clarified that oleuropein can suppress or improve the decrease in the motility of mature sperm due to heat stress, and prevent and improve mature sperm disorder.

Further, FIG. 3 shows the result of the motile sperm concentration calculated by multiplying the sperm concentration and the sperm motility rate. Motile sperm concentration represents the concentration of sperm that can actually be involved in fertilization and can be a more important indicator of male or male infertility.
The motile sperm concentration was also significantly lower in the hot heat treatment / oleuropein non-administration group than in the control (room temperature treatment), but the hot heat treatment / oleuropein administration group had good results equal to or better than the control. Met. In addition, the motile sperm concentration was significantly higher than that in the hot heat-treated / oleuropein non-administered group.

[4] Measurement of linear sperm velocity The linear velocity of sperm was measured using the above-mentioned sperm motility analysis system SMAS.

(result)
The measurement result of the linear velocity of sperm is shown in FIG.
Compared with the control (room temperature treatment), the linear velocity was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the hot heat treatment / oleuropein administration group had a linear velocity equal to or higher than that of the control, and the linear velocity was significantly higher than that of the hot heat treatment / oleuropein non-administration group. From this, it was clarified that oleuropein can suppress or improve the decrease in the linear velocity of mature sperm due to heat stress, and prevent and improve mature sperm disorder.

[5] Measurement of sperm curve velocity The sperm curve velocity was measured using the sperm motility analysis system SMAS.

(result)
The measurement result of the curve velocity of sperm is shown in FIG.
Compared with the control (room temperature treatment), the curve velocity was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the hot heat treatment / oleuropein administration group had a curve speed equal to or higher than that of the control, and the curve speed was significantly higher than that of the hot heat treatment / oleuropein non-administration group. From this, it was clarified that oleuropein can suppress or improve the decrease in the curve velocity of mature sperm due to heat stress, and prevent or improve mature sperm disorder.

[6] Measurement of average sperm velocity The curve velocity of spermatozoa was measured using the above-mentioned sperm motility analysis system SMAS.

(result)
The measurement result of the average sperm velocity is shown in FIG.
Compared with the control (room temperature treatment), the mean rate was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the hot heat treatment / oleuropein administration group had an average rate equal to or higher than that of the control, and the average rate was significantly higher than that of the heat treatment / oleuropein non-administration group. From this, it was clarified that oleuropein can suppress or improve the decrease in the average rate of mature sperm due to heat stress, and prevent or improve mature sperm disorder.

[7] Measurement of sperm head amplitude The sperm head amplitude was measured using the sperm motility analysis system SMAS.

(result)
The measurement result of the sperm head amplitude is shown in FIG.
Compared with the control (room temperature treatment), the head amplitude was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the heat-treated / oleuropein-administered group had the same head amplitude as the control, and the head amplitude was significantly higher than that of the heat-treated / oleuropein-non-administered group. From this, it was clarified that oleuropein can suppress the decrease in head amplitude of mature sperm due to heat stress and prevent and improve mature sperm disorder.

<7. Examination of the effect of oleuropein on improving spermatogenic ability (spermatogenic ability)>
Except for the fact that the mice were bred at room temperature after performing heat heat treatment for 15 minutes, the timing, dose, etc. of oleuropein administration were described in <6. Examination of the improvement effect of mature sperm disorder by oleuropein> was carried out, and sperm present in the testis and epididymal tail were collected 28 days later, and the following analysis was performed.

[1] Measurement of testis weight ratio The weights of the collected testis and the mouse were measured, and the testis weight ratio per mouse body weight was calculated.

(result)
The calculation result of the testis weight ratio is shown in FIG.
Compared with the control (room temperature treatment), the testis weight ratio tended to decrease in the hot heat treatment / oleuropein non-administration group. On the other hand, the testis weight ratio of the hot heat treatment / oleuropein administration group, which had been administered with oleuropein 5 days before the heat treatment, was almost the same as that of the control, and the testis weight ratio was higher than that of the heat treatment / oleuropein non-administration group. It showed a tendency. From this, it was clarified that oleuropein can prevent and improve the decrease in spermatogenic ability due to heat stress.

[2] Measurement of sperm concentration The same method as the above-mentioned method for measuring sperm concentration was performed.

The measurement result of sperm concentration is shown in FIG.
Compared with the control (room temperature treatment), the sperm concentration was clearly reduced in the hot heat treatment / oleuropein non-administration group. On the other hand, the hot heat treatment / oleuropein administration group had a sperm concentration equal to or higher than that of the control, and the sperm concentration was significantly higher than that of the heat treatment / oleuropein non-administration group. From this, it was clarified that oleuropein can prevent and improve the decrease in spermatogenic ability due to heat stress.

[3] Measurement of sperm motility The same method as the above-mentioned method for measuring sperm motility was performed.

The measurement result of the sperm motility is shown in FIG.
Compared with the control (room temperature treatment), the sperm motility tended to decrease in the hot heat-treated / oleuropein non-administered group and the hot-heated / oleuropein-administered group.

Further, FIG. 11 shows the result of the motile sperm concentration calculated by multiplying the sperm concentration and the sperm motility rate.
The motile sperm concentration was also significantly lower in the hot heat treatment / oleuropein non-administration group than in the control (room temperature treatment), but the hot heat treatment / oleuropein administration group had good results equal to or better than the control. Met. In addition, the motile sperm concentration was significantly higher than that in the hot heat-treated / oleuropein non-administered group.

The testicular disorder preventive and / or ameliorating agent of the present invention can be suitably used as pharmaceuticals, foods and drinks and feeds for infertility treatment of humans and animals, or for improving the production efficiency of industrial animals.

Claims (7)

Compounds having a hydroxytyrosol bone rated is contained as an active ingredient, an oral agent for the prevention and / or amelioration of testicular failure due to heat stress,
An oral preparation, wherein the compound is a compound selected from the group consisting of oleuropein and hydroxytyrosol . It said compound is contained in the olives, oral agent for the prevention and / or amelioration of testicular failure due to heat stress of claim 1. Compounds having a hydroxytyrosol bone rated is contained as an active ingredient, an oral medicament for the prevention and / or amelioration of testicular failure due to heat stress,
A pharmaceutical product, wherein the compound is a compound selected from the group consisting of oleuropein and hydroxytyrosol . Compounds having a hydroxytyrosol bone rated is contained as an active ingredient, a food or beverage for the prevention and / or amelioration of testicular failure due to heat stress,
A food or drink in which the compound is a compound selected from the group consisting of oleuropein and hydroxytyrosol . Compounds having a hydroxytyrosol bone rated is contained as an active ingredient, a feed for prevention and / or amelioration of testicular failure due to heat stress,
A feed in which the compound is a compound selected from the group consisting of oleuropein and hydroxytyrosol . A compound having a hydroxytyrosol bone price, the compound (excluding humans) oleuropein, and a compound selected from the group consisting of hydroxytyrosol, comprising orally administering the compound to male animals How to prevent and / or ameliorate testicular damage due to heat stress. Heat stress due for prevention and / or amelioration of testicular failure, oral pharmaceuticals, food and drink, or feed in the manufacture of, a compound having a hydroxytyrosol bone price, the oral pharmaceutical, food or beverage, or the feed is the use of as an active ingredient,
Use, wherein the compound is a compound selected from the group consisting of oleuropein and hydroxytyrosol .

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