Food composition for preventing or alleviating andropause syndrome, comprising fermented noni fermented with lactobacillus plantarum NST1805, and preparation method therefor

Abstract

The present application provides a food composition for preventing or alleviating andropause syndrome, comprising fermented noni fermented with Lactobacillus plantarum NST1805, and a preparation method therefor. More specifically, the present application provides a food composition for preventing or alleviating andropause syndrome and a preparation method therefor, the food composition being capable of efficiently preventing or alleviating andropause syndrome through regulation of male hormone production and / or improvement of sperm motility.

Description

Food composition for preventing or improving male menopausal syndrome, comprising fermented noni fermented with Lactobacillus plantarum NST1805, and method for producing the same

[0001] The present invention relates to a food composition for preventing or improving male menopausal syndrome, comprising fermented noni fermented with Lactobacillus plantarum NST1805, and a method for producing the same. More specifically, the present invention relates to a food composition for preventing or improving male menopausal syndrome, which can effectively prevent or improve male menopausal syndrome by regulating male hormone production and / or enhancing sperm motility, and a method for producing the same.

[0002] Menopause refers to the period in which various symptoms appear due to a decrease in sex hormones, and it also occurs in men in their late 30s as sex hormone secretion gradually decreases.

[0003] Male menopause refers to a series of symptoms and conditions resulting from physiological and endocrine changes in men after middle age. It is primarily caused by a gradual decline in testosterone levels, the primary male sex hormone, leading to various physical and mental changes. Representative symptoms include decreased energy, decreased libido, decreased muscle mass, depression, and sleep disturbances. Unlike female menopause, which involves rapid hormonal changes, male menopause is characterized by a gradual progression, and the severity and pattern of symptoms vary from person to person. Consequently, male menopause is often dismissed as a natural consequence of aging or mistaken for depression.

[0004] However, in modern medicine, awareness is increasing and it is being defined as male LOH (Late-Onset Hypogonadism), and it is becoming established as a health problem that needs to be actively managed.

[0005] Accordingly, interest in understanding and managing male menopause is growing, and the related market is steadily growing. However, research on effective treatment methods or preventive foods for improving or treating male menopause with minimal side effects is still lacking.

[0006] Current methods of testosterone supplementation include intramuscular injections, oral administration, and transdermal medications. However, intramuscular injections have been associated with problems such as abnormally high androgen concentrations, adverse reactions like breast pain, and the need to take them more than twice a day. Furthermore, oral hormones must be taken with a fatty meal and can cause indigestion. Furthermore, side effects such as increased red blood cell count, sleep apnea, benign prostatic hyperplasia, and prostate cancer have been reported when supplementing with testosterone through intramuscular or oral methods. Furthermore, transdermal medications have been associated with the potential for skin irritation.

[0007] Therefore, there is a need for the development of natural health functional foods and therapeutic compositions with minimal side effects that can be easily managed by individuals and alleviate the symptoms of male menopause syndrome with simple intake.

[0008] As a background technology of the present invention, a composition for preventing or treating male menopause syndrome containing rice bran extract is described in Korean Patent Publication No. 10-2020-0085156 (published on July 14, 2020).

[0009] The purpose of the present invention is to provide a food composition that can effectively prevent or improve male menopausal symptoms, including fermented noni.

[0010] Another object of the present invention is to provide a manufacturing method capable of efficiently manufacturing a food containing fermented noni that can prevent or improve male menopausal symptoms.

[0011] Another object of the present invention is to provide a pharmaceutical composition comprising fermented noni that can effectively prevent or treat male menopausal symptoms.

[0012] Other objects and advantages of the present invention will become more apparent from the detailed description, claims and drawings below.

[0013] According to one aspect, a food composition for preventing or improving male menopausal syndrome is provided, which comprises fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

[0014] According to one embodiment, the food composition of the present invention for preventing or improving male menopause syndrome can prevent or improve male menopause syndrome by controlling the expression of a gene that regulates the production of male hormones.

[0015] According to one embodiment, the food composition of the present invention for preventing or improving male menopausal syndrome can increase the expression of one or more of the genes LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 that promote the production of androgens.

[0016] According to one embodiment, the food composition of the present invention for preventing or improving male menopausal syndrome can reduce the expression of aromatase, a gene that converts testosterone into estradiol.

[0017] According to one embodiment, the food composition of the present invention for preventing or improving male menopause syndrome can increase the expression of androgen receptors.

[0018] According to one embodiment, the food composition of the present invention for preventing or improving male menopause syndrome can improve at least one of quadriceps femoris weight, sperm count, and sperm motility.

[0019]

[0020] According to another aspect, a pharmaceutical composition for preventing or treating male menopausal syndrome is provided, comprising fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

[0021] According to one embodiment, a pharmaceutical composition for preventing or treating male menopause syndrome can prevent or treat male menopause syndrome by controlling the expression of a gene that regulates androgen production.

[0022] According to one embodiment, a pharmaceutical composition for preventing or treating male menopausal syndrome can increase the expression of one or more of the genes LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 that promote androgen production.

[0023] In one embodiment, the pharmaceutical composition for preventing or treating male menopause syndrome can reduce the expression of the gene aromatase, which converts testosterone into estradiol.

[0024] In one embodiment, the pharmaceutical composition for preventing or treating male menopause syndrome can increase the expression of androgen receptors.

[0025] According to one embodiment, the pharmaceutical composition for preventing or treating male menopause syndrome can improve one or more of quadriceps femoris weight, sperm count, and sperm motility.

[0026]

[0027] According to another aspect, a method for producing a composition for preventing, improving, or treating male menopausal syndrome is provided, comprising: (1) a step of inoculating noni fruit with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) and fermenting and maturing the noni; and (2) a step of juicing the fermented noni obtained by the fermentation and maturation.

[0028] According to one embodiment, in the method for manufacturing a composition for preventing, improving, or treating male menopause syndrome of the present invention, the fermentation and maturation in step (2) may include a step of fermenting and maturating at 35 to 40°C for 20 to 120 days.

[0029] In one embodiment, the food composition or pharmaceutical composition of the present invention can effectively prevent, improve, or treat male menopausal syndrome by including fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

[0030] According to one embodiment, the food composition or pharmaceutical composition of the present invention can effectively prevent, improve, or treat male menopausal syndrome by controlling the expression of a gene that regulates the production of male hormones without side effects on the human body using a natural extract.

[0031] According to one embodiment, the method for producing a composition for preventing, improving, or treating male menopause syndrome of the present invention can efficiently produce a composition having a high effect in preventing, improving, or treating male menopause symptoms.

[0032] According to one embodiment, the method for producing a composition for preventing, improving, or treating male menopausal syndrome of the present invention is fermented with a single strain of Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P), so that the fermentation process is easy to control and productivity is high.

[0033] Figure 1 is a graph showing the results of measuring LHR gene expression (in vitro, TM3 Leydig cells) according to examples and comparative examples of the present invention.

[0034] Figure 2 is a graph showing the results of measuring StAR gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0035] Figure 3 is a graph showing the results of measuring CYP11A1 gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0036] Figure 4 is a graph showing the results of measuring 3β-HSD2 gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0037] Figure 5 is a graph showing the results of measuring 17,20-desmolase gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0038] Figure 6 is a graph showing the results of measuring 17β-HSD3 gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0039] Figure 7 is a graph showing the results of measuring aromatase gene expression (in vitro, TM3 Leydig cells) according to the examples and comparative examples of the present invention.

[0040] FIG. 8 is a graph showing the results of measuring FSHR (Follicle-Stimulating Hormone Receptor) gene expression (in vitro, TM4 Sertoli cells) when fermented noni fermented with a single strain of Lactobacillus plantarum NST1805 was treated at various concentrations according to one embodiment of the present invention.

[0041] FIG. 9 is a graph showing the results of measuring androgen receptor (AR) gene expression (in vitro, TM4 Sertoli cells) when fermented noni fermented with a single strain of Lactobacillus plantarum NST1805 at various concentrations according to one example of the present invention.

[0042] FIG. 10 is a graph showing the results of measuring the weight of the quadriceps femoris (in vivo) when fermented noni fermented with a single strain of Lactobacillus plantarum NST1805 at various concentrations according to one embodiment of the present invention.

[0043] FIG. 11 is a graph showing the results of measuring the number of sperm and sperm motility (in vivo) when fermented noni fermented with a single strain of Lactobacillus plantarum NST1805 at various concentrations according to one embodiment of the present invention.

[0044] The objects, advantages and features of the present invention will become more apparent from the following detailed description and examples in conjunction with the attached tables and drawings.

[0045] Prior to this, the terms or words used in this specification and claims should not be interpreted in their usual or dictionary meanings, but should be interpreted in their meanings and concepts that are consistent with the technical idea of ​​the present disclosure based on the principle that the inventor can appropriately define the concept of the term to explain his or her own invention in the best way.

[0046] The terminology used herein is for the purpose of describing specific embodiments only and is not intended to limit the present disclosure. Singular expressions include plural expressions unless the context clearly dictates otherwise.

[0047] In this application, terms such as “include” or “have” are intended to specify the presence of a feature, number, step, operation, component, part or combination thereof described in the specification, but should be understood not to exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts or combinations thereof.

[0048] In this application, when a part is said to "include" a certain component, this does not mean that it excludes other components, but rather that it may include other components, unless specifically stated otherwise.

[0049] In this specification, descriptions using the phrase "for example" or the like should not be construed as limiting the embodiments of the invention in terms of the effects of variations such as tolerances, measurement errors, limitations of measurement accuracy, and other commonly known factors, including the information presented, such as cited characteristics, variables, or values, which may not be exact matches.

[0050] The present invention is susceptible to various modifications and embodiments. Specific embodiments are illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, but rather to encompass all modifications, equivalents, and alternatives falling within the spirit and technical scope of the present invention. In describing the present invention, detailed descriptions of related known technologies will be omitted if they are deemed to obscure the gist of the present invention.

[0051] In this specification, “prevention” refers to all actions that suppress or delay male menopausal symptoms by administering the composition of this invention.

[0052] As used herein, “improvement” means at least reducing the severity of a symptom, for example, a parameter associated with a condition being treated by administration of the composition of the present invention.

[0053] In this specification, “treatment” means reversing, alleviating, inhibiting the progression of, or preventing male menopause symptoms by administering the composition of this invention.

[0054]

[0055] According to one aspect of the present invention, the food composition for preventing or improving male menopausal syndrome of the present invention includes fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

[0056] According to another aspect of the present invention, the pharmaceutical composition for preventing or treating male menopause syndrome of the present invention comprises fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

[0057] The present invention provides a composition for preventing, improving, and / or treating male menopause syndrome, including fermented noni, which is fermented with a single strain called Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) to maximize the efficacy of preventing or improving male menopause syndrome.

[0058] Our Lactobacillus plantarum NST1805 (Accession Number: KCCM12833P) strain can maximize the efficacy of fermented noni in preventing, improving, and / or treating male menopausal syndrome compared to other single strains and composite strains.

[0059] Our fermented noni includes all forms including fermented products, juices of fermented products, and concentrates thereof fermented with the strain Lactobacillus plantarum NST1805 (Accession Number: KCCM12833P).

[0060] Symptoms of andropause syndrome may vary in form and number from person to person. Although not limited to, the symptoms of andropause syndrome at our hospital may be at least one selected from the group consisting of hypogonadism, benign prostatic hyperplasia, lower urinary tract symptoms, nervousness, lethargy, chronic fatigue, decreased concentration, emotional instability, depression, abdominal obesity, tachycardia, sweating, facial flushing, sleep disorders, decreased energy, decreased work ability, decreased libido, erectile dysfunction, decreased energy, decreased physical strength, decreased exercise ability, and low testosterone.

[0061] Although not limited thereto, the food composition or pharmaceutical composition of the present invention can prevent, improve, and / or treat andropause syndrome by controlling the expression of genes that regulate androgen production.

[0062] Although not limited thereto, the food composition or pharmaceutical composition of the present invention can increase the expression of one or more of the genes LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 that promote the production of androgens.

[0063] The Luteinizing Hormone Receptor (LHR) is produced in Leydig cells of the testis. LHR binds to LH (luteinizing hormone), activating a signaling pathway that increases intracellular cAMP and thus activates the steroidogenic pathway. Activation of LHR triggers androgen and testosterone synthesis, increasing androgen production and potentially helping prevent and alleviate male menopausal symptoms.

[0064] StAR (Steroidogenic Acute Regulatory Protein) is involved in transporting cholesterol across the inner mitochondrial membrane. It is a protein that facilitates the production of pregnenolone during testosterone synthesis, which is then converted by enzymes into androgens, playing a role in the early stages of steroid hormone synthesis. Therefore, StAR expression may be effective in preventing and alleviating male menopausal syndrome by increasing androgen expression.

[0065] CYP11A1 (Cholesterol Side-Chain Cleavage Enzyme) converts cholesterol into pregnenolone, a precursor to steroid hormones, including androgens. Therefore, increased CYP11A1 expression may promote androgen synthesis, potentially helping prevent and alleviate male menopausal syndrome.

[0066] 3β-HSD2 (3β-Hydroxysteroid Dehydrogenase type 2) is an enzyme that converts pregnenolone to progesterone and 17-hydroxypregnenolone to 17-hydroxyprogesterone. This enzyme produces progesterone and androstenedione, ultimately contributing to testosterone synthesis. Therefore, increasing 3β-HSD2 expression may be effective in preventing and alleviating andropause syndrome.

[0067] 17,20-desmolase (CYP17A1) is a key enzyme that converts pregnenolone to dehydroepiandrosterone (DHEA) through 17α-hydroxylase and 17,20-lyase activities. DHEA is an androgen precursor, through which androstenedione and testosterone are synthesized. Therefore, increasing the expression of 17,20-desmolase (CYP17A1) may be effective in preventing and improving andropause syndrome.

[0068] 17β-HSD3 (17β-Hydroxysteroid Dehydrogenase type 3) is an enzyme that converts androgen precursors such as androstenedione into testosterone. This enzyme can produce testosterone by reducing the ketone group of androgen precursors such as androstenedione to a hydroxyl group. Therefore, increasing 17β-HSD3 expression may be effective in preventing and alleviating androgen-related symptoms.

[0069] Therefore, an increase in the expression of at least one of the LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 can activate androgen and testosterone synthesis through the interaction of enzymes and proteins, thereby performing androgen function, and thus can be effective in preventing, improving, and / or treating male menopausal symptoms.

[0070] Although not limited thereto, the food composition or pharmaceutical composition of the present invention can reduce the expression of the gene aromatase, which converts testosterone into estradiol.

[0071] Aromatase is an enzyme that converts testosterone into estrogen (primarily estradiol). Increased aromatase expression can lower overall testosterone levels. Increased aromatase activity can lead to decreased testosterone levels, which in turn can lead to muscle loss and impaired fat metabolism. This can lead to symptoms such as andropause, breast enlargement (gynecomastia), increased body fat, and mood swings.

[0072] Therefore, the food composition or pharmaceutical composition of the present invention can prevent, improve, and / or treat a decrease in male hormones by inhibiting the expression of aromatase.

[0073] Although not limited thereto, the food composition or pharmaceutical composition of the present invention can increase the expression of androgen receptor (AR).

[0074] The androgen receptor (AR) is a nuclear receptor activated by androgen hormones (primarily testosterone and dihydrotestosterone) within cells. Activated androgen receptors interact with testosterone in Sertoli cells, regulating cell differentiation, proliferation, autophagy, and spermatogenesis in the testis. Furthermore, they regulate various physiological functions, including male secondary sexual characteristics, muscle mass maintenance, sexual function, and bone health. However, androgen receptor expression may decrease with age, and even in the presence of sufficient testosterone, a deficiency of androgen receptors may reduce effects such as spermatogenesis, exacerbating the symptoms of androgen-related menopausal syndrome. Therefore, the food composition or pharmaceutical composition of the present disclosure can prevent, improve, and / or treat androgen-related menopausal syndrome by increasing androgen receptor expression.

[0075] Although not limited thereto, the food composition or pharmaceutical composition of the present invention can improve at least one of the following: quadriceps femoris weight, sperm count (sperm volume), and sperm motility.

[0076] The quadriceps, one of the major muscles, is influenced by testosterone levels. Testosterone plays a crucial role in muscle growth and maintenance, and as one of the major muscles, the quadriceps are significantly affected by testosterone levels.

[0077] Quadriceps femoris can lose weight due to decreased testosterone levels, which can lead to decreased muscle protein synthesis and decreased muscle mass. Lower body muscles, such as the quadriceps femoris, are particularly stimulated by daily activities and exercise, and testosterone deficiency can lead to decreased muscle size and weight, as well as decreased strength and function.

[0078] Because sperm count (sperm volume) is affected by testosterone, which plays a role in sperm production in the testes, a decrease in testosterone can lead to a decrease in sperm production.

[0079] Sperm motility is closely related to sperm morphology, mitochondrial activity, and testosterone levels. In particular, a decrease in testosterone can affect mitochondrial function involved in sperm energy production, which can lead to a decrease in sperm motility.

[0080] Quadriceps femoris weight, sperm count (sperm volume), and sperm motility are closely related to andropause, and a decrease in quadriceps femoris weight, a decrease in sperm count (sperm volume), and a decrease in sperm motility may be indicators of andropause syndrome. Therefore, the food composition or pharmaceutical composition of the present disclosure can effectively improve quadriceps femoris weight, sperm count (sperm volume), and sperm motility, thereby preventing, improving, and / or treating andropause syndrome.

[0081]

[0082] In this application, 'food composition' means a natural product or processed product containing one or more nutrients, preferably a product that has gone through a certain degree of processing to become directly edible, and in its usual sense, includes all foods, food additives, functional foods, and beverages.

[0083] In addition, in this application, the term 'preventive or improvement food composition' refers to a food group or food composition that has been designed and processed to sufficiently express the body's regulation function for regulating the biological defense rhythm, disease prevention, and recovery, etc., by using physical, biochemical, or bioengineering techniques to give added value to the food so that the food's function can be performed and expressed for a specific purpose.

[0084] Food compositions for preventing or improving male menopausal syndrome according to the present invention include, for example, various foods, beverages, gum, tea, vitamin complexes, health functional foods, etc. Furthermore, the food compositions of the present invention may contain additional ingredients such as various nutrients, vitamins, minerals (electrolytes), flavorings such as synthetic flavorings and natural flavorings, coloring agents and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages, and the above-mentioned additional ingredients may be used independently or in combination. The above-mentioned additional ingredients may be added in an appropriate amount within a range that does not inhibit the andropause syndrome prevention or improvement efficacy of fermented noni. For example, the above-mentioned additional ingredients may be included in an amount of 0.001 to 1 wt% based on the total weight of the above-mentioned food composition for preventing or improving andropause syndrome.

[0085] In addition, the amount of fermented noni extract or powder to be added to the health functional food of this invention may vary depending on the type of the target health functional food and cannot be uniformly regulated, but may be added within a range that does not damage the original taste of the food, and may be typically in the range of 0.01 to 100 wt%, 0.1 to 80 wt%, and 0.1 to 50 wt% with respect to the target food. In addition, in the case of health functional foods in the form of beverages, pills, granules, tablets, or capsules, may be added within the range of typically 0.1 to 100 wt%, and preferably 0.5 to 80 wt%.

[0086] In addition, the food composition for preventing or improving male menopausal syndrome of the present invention may include a food additive acceptable from a food science perspective, and may further include an appropriate carrier, excipient, and diluent commonly used in the manufacture of a food composition for preventing or improving male menopause syndrome.

[0087] The food composition for preventing or improving male menopause syndrome of this invention can be formulated in various forms, and thus its form is not particularly limited. Preferably, the food composition for preventing or improving male menopause syndrome may be formulated in any one form selected from the group consisting of a beverage, granules, tablets, powder, pills, and capsules.

[0088] The food composition for preventing or improving male menopause syndrome of this invention, having the form of a beverage, granule, tablet, powder, pill, or capsule, is easy to carry and can be easily consumed anytime, anywhere.

[0089] The composition for preventing or treating male menopause syndrome of this hospital may be used alone or in duplicate, or may be used in combination with a composition for preventing or treating male menopause syndrome of another hospital.

[0090] The composition for preventing or treating male menopause syndrome of this hospital may include fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) as an active ingredient.

[0091] Meanwhile, the term "comprising as an active ingredient" herein means including a sufficient amount to achieve the efficacy or activity of fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P). In one specific example of the present invention, the fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) in the composition of the present invention may be included in an amount of, for example, 0.001 mg / kg or more, preferably 0.1 mg / kg or more, more preferably 10 mg / kg or more, still more preferably 100 mg / kg or more, still more preferably 250 mg / kg or more, and most preferably 0.1 g / kg or more. Fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) is a natural product and does not cause side effects to the human body even when administered in excessive amounts. Therefore, the quantitative upper limit of fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) included in the composition of the present invention can be selected and implemented by a person skilled in the art within an appropriate range.

[0092] The pharmaceutical composition of the present invention can be manufactured using pharmaceutically suitable and physiologically acceptable auxiliary agents in addition to the above-mentioned effective ingredient, and the auxiliary agents can include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, glidants, or flavoring agents.

[0093] The above pharmaceutical composition may be preferably formulated as a pharmaceutical composition by additionally including one or more pharmaceutically acceptable carriers in addition to the above-described effective ingredients for administration.

[0094] The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants, and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracheacanth, or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, etc.

[0095] In the composition to be formulated as a liquid solution, acceptable pharmaceutical carriers include those that are sterile and biocompatible, such as saline solution, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures of one or more of these components. If necessary, other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate the composition into injectable formulations such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.

[0096] Furthermore, it can be preferably formulated according to the ingredient using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, as an appropriate method in the relevant field.

[0097] The pharmaceutical composition of this invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., and oral administration is preferred.

[0098] The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, patient age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity. A skilled physician can easily determine and prescribe a dosage effective for the desired treatment or prevention. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention may be 0.001 to 10 g per 1 kg of the subject's weight.

[0099] The pharmaceutical composition of the present invention may be manufactured in a unit dosage form or may be manufactured by inserting it into a multi-dose container by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains. In this case, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granule, tablet, or capsule, and may additionally include a dispersant or stabilizer.

[0100] According to another aspect, the method for preparing a composition for preventing, improving, and / or treating male menopause syndrome of the present invention comprises: (1) a step of inoculating noni fruit with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) and fermenting and maturing the fruit; and (2) a step of juicing the fermented noni obtained by the fermentation and maturation.

[0101] As described above, the method for manufacturing the composition for preventing, improving, and / or treating male menopause syndrome of this hospital comprises a step of inoculating a single strain called Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) and fermenting it, thereby making it easy to control the fermentation process and achieving high productivity.

[0102] Although not limited thereto, in the step (2), the fermentation and maturation may include a step of fermenting and maturating at 35 to 40°C for 20 to 120 days, and preferably a step of fermenting and maturating for 21 to 72 days. If the fermentation and maturation temperature is lower than 35°C, fermentation may not occur normally, and if it exceeds 40°C, the fermentation and maturation time becomes long, which may cause lactic acid bacteria to die, making it difficult to efficiently mass-produce a composition having excellent effects of preventing, improving, and / or treating andropause syndrome of fermented noni, and the taste and flavor of the beverage may deteriorate. In addition, when fermented and maturated for less than 20 days, fermentation may not occur sufficiently, which may deteriorate the taste and flavor, and when fermented for 120 days or more, over-fermentation may cause deterioration of the taste and flavor.

[0103] Although not limited thereto, in the present invention, the maturation may be performed by pouring the fermentation liquid produced during the fermentation process onto the top of the fermented product at regular intervals.

[0104] By maturing in this manner, bitterness and other flavors can be eliminated and the taste can be homogenized. Preferably, maturation can be accomplished by pouring the fermented liquid over the fermented product at intervals of 5 to 10 days. If the interval between pouring the fermented liquid over the fermented product is 5 days or less (e.g., every 3 days) or 10 days or more (e.g., every 11 days), a bitter taste may remain.

[0105]

[0106] Hereinafter, the present invention will be described in more detail through examples. However, these examples are intended solely to illustrate the present invention, and the scope of the present invention is not to be construed as being limited by these examples.

[0107]

[0108] Example. Preparation of Fermented Morinda citrifolia Extract (FME_3)

[0109] Morinda citrifolia fruits harvested in Indonesia were used. The harvested noni fruits were washed twice and stored frozen at -27°C. The frozen noni was thawed at 37°C for 48 h, inoculated with L. plantarum NST 1805 culture (2.0% v / w), and fermented at 37°C for 60 days. The fermented noni was then filtered through filter paper and a vacuum filter (80 mesh) to remove foreign substances and impurities. The resulting extract was concentrated to 60 ± 5 Brix, sterilized, and stored at -20°C for subsequent use in the experiments.

[0110] Comparative Example 1. Preparation of non-fermented noni extract (ME)

[0111] Morinda citrifolia fruit harvested in Indonesia was used. The harvested noni fruit was washed twice and stored frozen at -27°C. The frozen noni was thawed at 37°C for 48 hours, then incubated and aged for 60 days with an equal volume of sterilized water. The noni was then filtered through paper and a vacuum filter (80 mesh) to remove foreign substances and impurities. The resulting extract was concentrated to 60 ± 5 Brix, sterilized, and stored at -20°C for subsequent use in the experiments.

[0112] Comparative Example 2. Production of Fermented Morinda citrifolia Extract (FME_1)

[0113] Instead of the L. plantarumNST 1805 culture medium of the example, Lactiplanti bacillus. rhamnosusR1 was inoculated and used, and all other process conditions were the same as in the example.

[0114] Comparative Example 3. Production of Fermented Morinda citrifolia Extract (FME_2)

[0115] Instead of the L. plantarumNST 1805 culture medium of the example, a mixed lactic acid bacteria of 7 types (Lactobacillus plantarum 60 to 65 wt%; Bifidobacterium lactis 10 to 15 wt%; Lactobacillus rhamnosus 5 wt%; Lactobacillus casei 1 to 10 wt%; Lactobacillus fermentum 1 to 10 wt%; Bifidobacterium breve 1 to 10 wt%; and Lactococcus lactis subspicious lactis 1 to 10 wt%) was inoculated and used, and all other process conditions were the same as in the example.

[0116]

[0117] Experimental example

[0118] 1. Cell culture

[0119] TM3 cells (mouse Leydig cells) and TM4 cells (mouse Sertoli cells) were purchased from the Korea Cell Line Bank (Seoul, South Korea) and cultured in Dulbecco's modified Eagle's medium (DMEM; HyClone, Logan, UT, USA) supplemented with 10% FBS (Gibco BRL, Life Technologies Co., New York, NY, USA) and 1% antibiotics (Welgene, Daegu, South Korea). Cells were maintained at 37°C with 5% CO2 and passaged every 3 days. Oxidative stress was induced by replacing the medium with serum-free medium supplemented with 100 μM hydrogen peroxide (Sigma-Aldrich, St. Louis, MO, USA) and incubating for 4 h. Samples were then treated with various concentrations and incubated for 24 h before collecting the cells and medium for experiments.

[0120] 2. Laboratory animals

[0121] Eight- and 32-week-old male Sprague Dawley (SD) rats were purchased from Jungang Laboratory Animal Co., Ltd. The animals were housed in a breeding environment set at 23±3℃, 50±10% relative humidity, 12-hour lighting schedule, and 150–300 Lux of light. Throughout the entire experiment, the animals were allowed free access to solid food and water for laboratory animals. After a one-week acclimatization period, the animals were divided into the following groups: the control group (administered only saline), the 300 mg / kg Testofen (positive control group), the 125 mg / kg FME group, the 250 mg / kg FME group, and the 500 mg / kg FME group, with nine animals per experimental group. The test substances were dissolved in saline and administered orally at regular times for 4 weeks. The control group was administered orally the same volume of saline containing no extract.

[0122] 3. Quantitative Real-Time PCR (qRT-PCR) Analysis

[0123] Total RNA was isolated from cells using the easy-Blue™ kit (iNtRON, Seongnam, South Korea), and cDNA was synthesized using the High-Capacity RNA-to-cDNA kit (Thermo Fisher Scientific, Waltham, MA, USA). Template DNA was prepared using AccuPrep ® Genomic DNA was extracted using a genomic DNA extraction kit (Bioneer, Daejeon, South Korea). Quantification was performed over 40 cycles under the following culture conditions: 48°C for 15 minutes, 95°C for 10 minutes, 95°C for 15 seconds, and 60°C for 1 minute. Data analysis was performed using StepOne Software v2.3. The expression of the GAPDH housekeeping gene was normalized using a mathematical model of relative expression ratios that account for PCR efficiency. The primer sequences used are listed in Table 1. Table 1 shows the primer sequences for qRT-PCR used.

[0124]

[0125] 4. Measurement of sperm count and sperm motility

[0126] After sacrificing the experimental animals, the left and right epididymis were removed, weighed, and then finely chopped and homogenized in a container containing 1 mL of M199 media (Gibco) containing 0.5% bovine serum albumin (BSA, Sigma-Aldrich Co.). 50 μL of the homogenate was diluted with 950 μL of M199 media containing 0.5% BSA. To measure the sperm count, a certain amount of the left epididymis homogenate was evenly distributed into a hemocytometer, and the sperm count was measured under a light microscope. To measure sperm motility, the right epididymis homogenate was incubated at 37°C for 5 minutes, then evenly distributed into a hemocytometer, and motility was observed under a light microscope. 100 sperm per individual were observed for motility. Sperm motility was counted and classified into three categories: progressive, non-progressive, and immotile, based on the WHO sperm motility measurement guidelines.

[0127] 5. Statistical analysis

[0128] Experimental results are expressed as mean ± standard deviation, and statistical significance was verified using Student's t-test. P values ​​less than 0.05 were considered statistically significant and are marked with a single asterisk (*). P values ​​less than 0.01 were marked with a double asterisk (**), and P values ​​less than 0.001 were marked with a triple asterisk (***).

[0129] 6. Results

[0130] 6-1. Increased gene expression of LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3.

[0131] According to one experimental example described herein, the composition of the present invention was confirmed to be effective in preventing and improving male menopausal syndrome by increasing the gene expression levels of LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3, which promote an increase in male hormones.

[0132]

[0133] According to Fig. 1 and Table 2, the LHR gene expression level showed the highest average value (0.91) in the fermented noni extract of L. plantarumNST 1805 prepared according to one example of the present invention compared to the control group. When LHR is activated, the androgen and testosterone synthesis process is triggered, thereby increasing the production of male hormones, which may be effective in preventing and improving male menopausal syndrome.

[0134] In particular, it was confirmed that the average value of gene expression was higher and the standard deviation was lower than that of the fermented noni extract fermented with 7 types of mixed lactic acid bacteria, making it easier to control fermentation conditions and showing superior results using simpler processes and materials.

[0135]

[0136] According to Fig. 2 and Table 3, the StAR gene expression level was the highest (0.93) in the fermented noni extract of L. plantarum NST 1805 prepared according to one example of the present invention compared to the control group. The high expression level of StAR acts to increase the expression of male hormones, and thus may be effective in preventing and improving male menopausal syndrome.

[0137] In particular, it was confirmed that the average value of gene expression was higher and the standard deviation was lower than that of the fermented noni extract fermented with 7 types of mixed lactic acid bacteria, making it easier to control fermentation conditions and showing superior results using simpler processes and materials.

[0138]

[0139] According to Fig. 3 and Table 4, the CYP11A1 gene expression level was the highest (0.82) in the fermented noni extract of L. plantarum NST 1805 prepared according to one example of the present invention compared to the control group. An increase in CYP11A1 can promote androgen synthesis and thus be effective in preventing and improving male menopausal syndrome.

[0140]

[0141] According to Fig. 4 and Table 5, the 3β-HSD2 gene expression level was the highest (0.85) in the fermented noni extract of L. plantarumNST 1805 prepared according to one example of the present invention compared to the control group. The increase in 3β-HSD2 contributes to testosterone synthesis and thus may be effective in preventing and improving male menopausal syndrome.

[0142] In particular, it was confirmed that the average value of gene expression was higher and the standard deviation was lower than that of the fermented noni extract fermented with 7 types of mixed lactic acid bacteria, making it easier to control fermentation conditions and showing superior results using simpler processes and materials.

[0143]

[0144] According to Fig. 5 and Table 6, the expression level of 17,20-desmolase gene was the highest (0.86) in the fermented noni extract of L. plantarumNST 1805 prepared according to one example of the present invention compared to the control group. The increase in 17,20-desmolase (CYP17A1) activates androgen precursors to synthesize testosterone, so it may be effective in preventing and improving male menopausal syndrome.

[0145]

[0146] According to Fig. 6 and Table 7, the 17β-HSD3 gene expression level was the highest (0.82) in the fermented noni extract of L. plantarumNST 1805 prepared according to one example of the present invention compared to the control group. An increase in 17β-HSD3 contributes to testosterone production and thus may be effective in preventing and improving male menopausal syndrome.

[0147] In particular, it was confirmed that the average value of gene expression was higher and the standard deviation was lower than that of the fermented noni extract fermented with 7 types of mixed lactic acid bacteria, making it easier to control fermentation conditions and showing superior results using simpler processes and materials.

[0148] 6-2. Decreased aromatase gene expression

[0149] According to one experimental example described herein, it was confirmed that the composition of the present invention is effective in preventing and improving male menopausal syndrome by reducing the expression level of aromatase, which converts testosterone into estradiol.

[0150]

[0151] According to Fig. 7 and Table 8, the aromatase gene expression level was the lowest (1.38) in the fermented noni extract of L. plantarum NST 1805 prepared according to one example of the present invention compared to the control group. It was confirmed that the low activity of aromatase is effective in preventing and improving male menopausal syndrome by preventing the conversion of testosterone to estrogen and thus suppressing the decrease in androgen levels.

[0152] 6-3. Increase in gene expression of FSHR and androgen receptor (AR) (in vitro, TM4 Sertoli cells) when fermented noni with NST1805 single strain according to one example of the present invention

[0153]

[0154] According to Figure 8 and Table 9, the higher the content of fermented noni treated with the single NST1805 strain, the higher the FSHR expression level. FSHR mRNA expression decreased by 50.60% after H2O2 treatment compared to untreated cells and significantly increased after FME treatment (p < 0.05).

[0155] FSHR is a receptor that regulates reproductive function in both men and women. It primarily binds to follicle-stimulating hormone (FSH) to regulate the maturation and development of germ cells. FSHR is a receptor that contributes to male reproductive function, particularly sperm production. When testosterone levels decline during andropause, the pituitary gland compensates by increasing the secretion of FSH and LH (luteinizing hormone). When FSHR is sufficiently expressed and functioning in the testes, sperm production can be maintained even with elevated FSH levels. However, when FSHR function is impaired, sperm production can decline even with high FSH levels.

[0156] Therefore, the results of this experiment suggest that high FSHR levels may be effective in maintaining sperm production, and thus, it can be predicted to be effective in preventing and improving male menopausal syndrome.

[0157]

[0158] According to Figure 9 and Table 10, the higher the content of fermented noni treated with the NST1805 single strain, the higher the androgen receptor expression. AR mRNA levels decreased by 76.30% compared to untreated cells, but significantly increased with FME treatment (p < 0.05).

[0159] Therefore, the results of this experiment suggest that the level of androgen receptors increases and increases with the fermented noni content, which may be effective in maintaining sperm production and thus in preventing and improving male menopausal syndrome.

[0160] 6-4. According to one example of the present invention, the weight of the quadriceps femoris increased when fermented noni from a single strain of NST1805 was treated.

[0161]

[0162] According to Fig. 10 and Table 11, it was confirmed that the weight of the quadriceps femoris increased as the content of NST1805 single strain fermented noni increased.

[0163] Therefore, it is presumed that muscle loss was prevented by preventing and improving the decrease in male hormones, and it can be predicted to be effective in preventing and improving male menopausal syndrome.

[0164] 6-5. According to one example of the present invention, the number of sperm and sperm motility increased when fermented noni with a single strain of NST1805 was treated.

[0165]

[0166] According to Fig. 11 and Table 12, it was confirmed that the higher the content of NST1805 single strain fermented noni, the better the sperm count and sperm motility.

[0167] Therefore, it can be predicted that the number of sperm and sperm motility indices, which are sensitive to the increase or decrease of testosterone, are excellent, and thus it is effective in preventing and improving male menopausal syndrome by preventing and improving the decrease in androgens.

[0168]

[0169] Above, one embodiment of the present invention has been described, but a person having ordinary skill in the art will be able to modify and change the present invention in various ways by adding, changing, deleting or adding components, etc., within the scope that does not depart from the spirit of the present invention described in the claims, and this is also included within the scope of the rights of the present invention.

[0170]

[0171] [Accession number]

[0172] Name of depositor: Korea Center for Microbiological Conservation (KCCM)

[0173] Accession number: KCCM12833P

[0174] Date of acceptance: 20201117

[0175]

Claims

1. A food composition for preventing or improving male menopausal syndrome, comprising fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

2. In paragraph 1, A food composition for preventing or improving male menopause syndrome, which prevents or improves male menopause syndrome by controlling the expression of genes that regulate male hormone production.

3. In paragraph 1, A food composition for preventing or improving male menopausal syndrome, which increases the expression of at least one of the genes LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 that promote the production of male hormones.

4. In paragraph 1, A food composition for preventing or improving male menopausal syndrome, which reduces the expression of aromatase, a gene that converts testosterone into estradiol.

5. In paragraph 1, A food composition for preventing or improving male menopausal syndrome, which increases the expression of androgen receptors.

6. In paragraph 1, A food composition for preventing or improving male menopause syndrome, which improves at least one of quadriceps femoris weight, sperm count, and sperm motility.

7. A pharmaceutical composition for preventing or treating male menopausal syndrome, comprising fermented noni fermented with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P).

8. In paragraph 7, A pharmaceutical composition for preventing or treating male menopause syndrome, which prevents or treats male menopause syndrome by controlling the expression of genes that regulate the production of male hormones.

9. In paragraph 7, A pharmaceutical composition for preventing or treating male menopausal syndrome, which increases the expression of at least one of the genes LHR, StAR, CYP11A1, 3β-HSD2, 17,20-desmolase, and 17β-HSD3 that promote the production of androgens.

10. In paragraph 7, A pharmaceutical composition for preventing or treating male menopausal syndrome, which reduces the expression of the gene aromatase that converts testosterone into estradiol.

11. In paragraph 7, A pharmaceutical composition for preventing or treating male menopausal syndrome, which increases the expression of androgen receptors.

12. In paragraph 7, A pharmaceutical composition for preventing or treating male menopause syndrome, which improves at least one of quadriceps femoris weight, sperm count, and sperm motility. 13.(1) A step of inoculating noni fruit with Lactobacillus plantarum NST1805 (Accession No.: KCCM12833P) and fermenting and maturing it; and (2) A method for producing a composition for preventing, improving, or treating male menopause syndrome, comprising a step of extracting the fermented noni obtained through the above fermentation and maturation.

14. In paragraph 13, A method for producing a composition for preventing, improving, or treating male menopause syndrome, comprising the step of fermenting and maturing at 35 to 40°C for 20 to 120 days in step (2).

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