Composition for treating menstruation-related disease or symptom

Abstract

Provided is a composition for preventing and / or ameliorating premenstrual or postmenstrual discomfort or for preventing and / or ameliorating a menstruation-related disease or symptom.　Also provided is a Nannochloropsis-containing composition for preventing and / or ameliorating premenstrual or postmenstrual discomfort or for preventing and / or ameliorating a menstruation-related disease or symptom.

Description

Compositions for the treatment of menstruation-related diseases or conditions

[0001] The present invention relates to compositions for the treatment of menstruation-related diseases or conditions.

[0002] Adenomyosis is a disease in which tissue similar to the endometrium forms within the uterine muscles, causing the walls of the uterus to thicken and the entire uterus to enlarge.The main symptoms are menstrual pain, menorrhagia, and anemia associated with menorrhagia.

[0003] On the other hand, Nannochloropsis is a genus of algae that has been known for a long time (Non-Patent Document 1), and contains more than 60 types of nutrients, including ω3 series eicosapentaenoic acid and ω7 series palmitoleic acid, and is used in a wide range of industries, such as fish and shellfish feed in aquaculture, livestock feed in livestock farming, fertilizer in agriculture, and food supplements.

[0004] Perspectives in Phycology 4(1): DOI: 10.1127 / pip / 2016 / 0065

[0005] The problem to be solved by the present invention is to provide a composition for the treatment of menstruation-related diseases or symptoms.

[0006] The present invention encompasses, for example, the following subjects. Item 1. A composition containing Nannochloropsis for preventing and / or improving premenstrual and / or menstrual disorders, or for preventing and / or improving menstrual-related diseases or symptoms. Item 2. The composition according to Item 1, which is a composition for preventing and / or improving menstrual-related diseases or symptoms, wherein the menstrual-related diseases or symptoms include at least one selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia. Item 3. The composition according to Item 1, which is a composition for preventing and / or improving premenstrual and / or menstrual disorders. Item 4. The composition according to any one of Items 1 to 3, which contains Nannochloropsis powder. Item 5. The composition according to any one of Items 1 to 4, which is a food composition. Item 6. The composition according to any one of Items 1 to 4, which is a pharmaceutical composition. Item 7. Use of Nannochloropsis in the manufacture of a composition for preventing and / or improving premenstrual and / or menstrual disorders, or for preventing and / or improving menstrual-related diseases or symptoms.

[0007] According to the present invention, menstruation-related diseases or symptoms can be effectively treated.

[0008] In this specification, the term "comprise" is a concept that encompasses "consist essentially only of" and "consist only of."

[0009] As used herein, "prevention and / or improvement" can also be expressed as "both prevention and improvement, or either one of prevention and improvement." Therefore, "prevention and / or improvement" of the present invention includes (1) prevention and improvement, (2) prevention, and (3) improvement. Furthermore, as used herein, "improvement" can also be expressed as "treatment."

[0010] The following describes further embodiments of the present invention. Note that the embodiments described below are examples of typical embodiments of the present invention, and are not intended to limit the scope of the invention.

[0011] The composition of the present invention for preventing and / or ameliorating menstruation-related diseases or symptoms contains Nannochloropsis, particularly as an active ingredient.

[0012] Nannochloropsis is a "Eukaryote / Stramenopyra / Heterokontophyta / Eustigmatophyceae / Eustigmatophyceae / Genus Nannochloropsis". It is a unicellular alga that is exceptionally green among heterokontophytes. While most heterokontophytes grow in freshwater or soil, the genus Nannochloropsis is an exception, growing in the ocean. Seven species of Nannochloropsis are known: Nannochloropsis australis, Nannochloropsis gaditana, Nannochloropsis granulata, Nannochloropsis limnetica, Nannochloropsis oceanica, Nannochloropsis oculata, and Nannochloropsis salina, and they are currently cultivated on a large scale in Japan.

[0013] Nannochloropsis powder or concentrate obtained by culturing Nannochloropsis by known methods may be used in the composition of the present invention, or Nannochloropsis powder or concentrate may be purchased from a supplier.

[0014] Preferably, the Nannochloropsis in the composition of the present invention comprises Nannochloropsis powder, which can be obtained by filtering a culture solution containing Nannochloropsis and powdering the resulting Nannochloropsis, and examples of methods for powdering include a spray dryer method in which the filtered liquid Nannochloropsis is sprayed and instantly dried with hot air, and a method in which the filtered Nannochloropsis is freeze-dried and then pulverized in a grinder.

[0015] The subject to which the composition of the present invention is ingested or administered is a human.

[0016] The content of Nannochloropsis in the composition of the present invention may be any amount sufficient to achieve the desired effect. The dosage or intake of the composition can be appropriately determined taking into account various factors, such as the age, body weight, and symptoms of the subject. The daily amount of Nannochloropsis can be, for example, 50 mg or more, preferably 100 mg or more. The upper limit of the content per single dose or daily dose can be 20 g or less, preferably 10 g or less, regardless of the lower limit. The composition is taken in divided doses 1 to 4 times per day, preferably 1 to 3 times per day. The daily amount of Nannochloropsis per body weight can be, for example, 1 mg / kg or more, preferably 2 mg / kg or more. The upper limit of the content per single dose or daily dose can be 400 mg / kg or less, preferably 200 mg / kg or less, regardless of the lower limit.

[0017] The amount of Nannochloropsis per administration or per meal can be, for example, 25 mg or more, preferably 50 mg or more. The upper limit of the content per dose or per day, regardless of the lower limit, can be 20 g or less, preferably 10 g or less.

[0018] Preferably, the Nannochloropsis in the composition of the present invention has a palmitoleic acid content of 5 g or more per 100 g of fatty acid composition, as determined by component analysis by the Japan Food Research Laboratories. This palmitoleic acid content is 30 to 40 times that of other algae. Palmitoleic acid is known to have anti-inflammatory effects, improving the intestinal environment and preventing inflammation.

[0019] The compositions of the present invention may also contain other active or nutrient ingredients that are food or pharmaceutically acceptable, such as amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), peptides, proteins, carbohydrates, lipids, electrolytes (e.g., sodium, potassium, calcium, magnesium), vitamins, minerals, organic acids, herbs, herbal extracts, and antibiotics.

[0020] The composition of the present invention may further contain additives acceptable for use as foods or pharmaceuticals, such as inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, flavoring agents, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavorings, acidulants, and natural products. More specifically, examples of the additives include water, other aqueous solvents, pharmaceutically acceptable organic solvents, finely divided silicon dioxide, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, calcium stearate, human serum albumin, crystalline cellulose, hydroxypropyl cellulose, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, and vegetable juice.

[0021] The composition of the present invention containing Nannochloropsis is particularly effective in preventing and / or improving premenstrual disorders in women, and can be used to treat diseases or symptoms resulting from a disturbance (e.g., an increase or decrease) in sex hormones (especially female hormones) or diseases or symptoms related to menstruation. Premenstrual disorders in women include premenstrual syndrome (PMS). PMS can be evaluated based on one or more symptoms selected from the group consisting of breast tenderness / pain, rough skin, vaginal discharge, onset / worsening of allergic symptoms, headache / heavy headache, stiff shoulders, dizziness, abdominal pain / lower abdominal distension, edema (swelling), appetite changes (overeating / loss of appetite), digestive symptoms (diarrhea / constipation), changes in taste, sleep disorders, depression / autism, irritability / aggression, tearfulness / loneliness / isolation / anxiety, decreased concentration / decreased efficiency, menstrual flow, menstrual pain, and anemia. Improvement of these symptoms indicates the effectiveness of the composition of the present invention containing Nannochloropsis in preventing and / or ameliorating PMS. Examples of treatment for menstruation-related diseases or symptoms include uterine adenomyosis, menstrual pain, menorrhagia, anemia, etc. Preferably, the composition of the present invention containing Nannochloropsis can be used to treat at least one disease or symptom selected from the group consisting of uterine adenomyosis, menstrual pain, menorrhagia, and anemia.

[0022] The composition of the present invention containing Nannochloropsis can be used to treat at least one menstruation-related disease or symptom selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia. Treatment includes suppressing, inhibiting, or reducing the onset or manifestation (expression) of the target disease or condition, reducing the risk of its onset or manifestation, treating the onset or manifestation of the target disease or condition, or suppressing, inhibiting, or slowing the progression of the target disease or condition.

[0023] The composition of the present invention may be administered parenterally, for example enterally, or orally, but is preferably administered orally.

[0024] In some preferred embodiments, the composition of the present invention for preventing and / or ameliorating at least one menstruation-related disease or symptom selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia is a food composition.

[0025] When the composition of the present invention is a food, it may be a food with health claims such as a food for specified health uses, a food with nutrient functions, or a food with functional claims, or may be a general food, or may be in the form of a food supplement.

[0026] The food composition of the present invention may be prepared in any form, such as a solid, liquid, mixture, suspension, thickened liquid, powder, granules, paste, sol, gel, capsule, etc. In the case of a solid form, it may be in the form of a tablet, granule, powder, pill, capsule, etc.

[0027] In some preferred embodiments, the composition of the present invention for preventing and / or ameliorating at least one menstruation-related disease or symptom selected from the group consisting of uterine adenomyosis, menstrual pain, menorrhagia, and anemia is a pharmaceutical composition.

[0028] The pharmaceutical composition of the present invention can be made into any dosage form suitable for oral administration, such as solid preparations such as tablets, granules, powders, pills, and capsules; liquid preparations such as solutions, suspensions, and syrups; and gels.

[0029] The unit amount per administration or meal as a composition is, for example, 50 mg to 50 g, preferably 100 mg to 20 g, and more preferably 150 mg to 10 g. The unit amount per meal may be the daily dose, or may be 1 / 2 to 1 / 10 of the daily dose by dividing the daily dose.

[0030] The composition of the present invention can be labeled to the effect that it can be used to treat the symptoms described above, and can also be labeled to recommend its ingestion to the subjects described above. Labeling can be direct or indirect. Examples of direct labeling include descriptions on tangible objects such as the product itself, packaging, containers, labels, tags, etc., and examples of indirect labeling include advertising and promotional activities by place or means such as websites, stores, exhibitions, books, newspapers, magazines, television, radio, mail, email, and voice.

[0031] The composition of the present invention is femtech, and supports the resolution of women's health issues and their participation in society.

[0032] The present invention also provides the following: Item 1. A composition containing Nannochloropsis for preventing and / or improving premenstrual and / or menstrual discomfort, or for preventing and / or improving menstrual-related diseases or symptoms. Item 2. The composition according to Item 1, which is a composition for preventing and / or improving menstrual-related diseases or symptoms, wherein the menstrual-related diseases or symptoms include at least one selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia. Item 3. The composition according to Item 1, which is a composition for preventing and / or improving premenstrual and / or menstrual discomfort. Item 4. The composition according to Item 3, which is a composition for preventing and / or improving premenstrual syndrome (PMS). Item 5. The composition according to any one of Items 1 to 4, which contains Nannochloropsis powder. Item 6. The composition according to Item 1, which is a composition for preventing and / or improving adenomyosis. Item 7. The composition according to Item 1, which is a composition for preventing and / or improving menstrual pain. Item 8. Item 1. The composition according to Item 1, which is a composition for preventing and / or improving menorrhagia. Item 9. The composition according to Item 1, which is a composition for preventing and / or improving anemia. Item 10. The composition according to any one of Items 1 to 9, which is a food composition. Item 11. The composition according to Item 10, which is a composition for preventing and / or improving adenomyosis. Item 12. The composition according to Item 10, which is a composition for preventing and / or improving menstrual pain. Item 13. The composition according to Item 10, which is a composition for preventing and / or improving menorrhagia. Item 14. The composition according to Item 10, which is a composition for preventing and / or improving anemia. Item 15. The composition according to Item 10, which is a composition for preventing and / or improving premenstrual syndrome. Item 16. The composition according to any one of Items 1 to 9, which is a pharmaceutical composition. Item 17. The composition according to Item 16, which is a composition for preventing and / or treating adenomyosis. Item 18. Item 16. The composition according to Item 16, which is a composition for preventing and / or treating menstrual pain. Item 19. The composition according to Item 16, which is a composition for preventing and / or treating menorrhagia. Item 20. The composition according to Item 16, which is a composition for preventing and / or treating anemia. Item 21. The composition according to Item 16, which is a composition for preventing and / or treating premenstrual syndrome.Item 22. The composition according to any one of Items 1 to 21, further comprising an additive acceptable as a food or pharmaceutical. Item 23. A non-therapeutic method for preventing and / or ameliorating premenstrual and / or postmenstrual disorders, or preventing and / or ameliorating menstrual-related diseases or symptoms in a subject, comprising orally administering the composition according to any one of Items 1 to 22 to the subject. Item 24. The method according to Item 23, wherein the menstrual-related disease or symptom includes at least one selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia. Item 25. The method according to Item 23, wherein the premenstrual and / or postmenstrual disorders include premenstrual syndrome (PMS). Item 26. Use of Nannochloropsis in the manufacture of a product for preventing and / or ameliorating premenstrual and / or postmenstrual disorders, or preventing and / or ameliorating menstrual-related diseases or symptoms. Item 27. The use according to Item 26, wherein the menstrual-related disease or symptom includes at least one selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia. Item 28. The use according to Item 26, wherein the premenstrual and postmenstrual disorders include premenstrual syndrome (PMS). Item 29. The use according to any one of Items 26 to 28, wherein the composition further contains an additive acceptable as a food or pharmaceutical. Item 30. The use according to any one of Items 26 to 28, wherein the composition is a food composition. Item 31. The use according to any one of Items 26 to 28, wherein the composition is a pharmaceutical composition.

[0033] The following examples are intended for illustrative purposes only and are not intended to limit the scope of the present invention in any way. Unless otherwise specified, reagents are commercially available or are obtained or prepared according to conventional techniques or literature procedures in the art.

[0034] Example 1: A 40-year-old woman began taking a Nannochloropsis-containing supplement (trade name "Nannochloropsis," 180 tablets, marketed by Green Algae Tech JAPAN Co., Ltd.) in July 2023. The supplement contained Nannochloropsis powder (approximately 70% by weight of the supplement) and the remaining additives such as excipients (crystalline cellulose, hydroxypropyl cellulose, calcium stearate, and fine silicon dioxide). According to an analysis by the Japan Food Research Laboratories, the fatty acid composition of the supplement is shown in Table 1, and the vitamin composition is shown in Table 2.

[0035] This woman had been suffering from uterine enlargement due to uterine adenomyosis since she was 20 years old, and had symptoms of menstrual pain and excessive bleeding (menorrhagia). After six months of taking the drug, the pain eased and the bleeding decreased, and the doctor diagnosed her with normal anemia and endoscopy results at a regular checkup in April 2024 (at Watanabe Obstetrics and Gynecology, Iwaki City, Fukushima Prefecture).

[0036]

[0037]

[0038] Example 2: Nannochloropsis was used in a study on three female subjects, Subjects A-C (A: 47 years old, B: 20 ​​years old, C: 49 years old), who were 20 years of age or older at the start of the study and experiencing physical and mental discomfort associated with menstruation. 1. Study Period: May 1, 2025 to August 5, 2025. 2. Intake Method: The same Nannochloropsis supplement used in Example 1 (3 tablets per day) was taken daily on an empty stomach between 1:00 AM and 8:00 AM before dawn or before breakfast. 3. Questionnaire Response Schedule: Subjects were asked to report their usual symptoms before and during their menstrual periods. After starting the supplement, they were asked to report their symptoms during their first and second menstrual periods. However, Subject A did not experience her second period after starting the supplement, and so was unable to provide questionnaire responses for the premenstrual and menstrual periods. They were asked to write freely about the changes they felt after the end of three menstrual cycles.

[0039]

[0040] 4. Questionnaire items The questionnaire items and scores were as follows: (1) Breast tenderness / pain 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (2) Rough skin 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (3) Vaginal discharge 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (4) Appearance / worsening of allergy symptoms 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (5) Headache / heavy headache 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (6) Stiff shoulders 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (7) Dizziness 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (8) Abdominal pain / lower abdominal distension 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (9) Edema (swelling) 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (10) Changes in appetite (overeating / loss of appetite) 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (11) Digestive symptoms (diarrhea / constipation) 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (12) Changes in taste (craving different foods) 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (13) Insomnia / able to sleep for any length of time 0 (none) 1 (a little) 2 (yes) 3 (quite often) 4 (severe) (14) Depression / autism 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (15) Irritability / aggression 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (16) Tearfulness / loneliness / isolation / anxiety 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (17) Decreased concentration / efficiency 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (18) Menstrual flow 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (19) Menstrual pain 0 (none) 1 (a little) 2 (some) 3 (quite a lot) 4 (severe) (20) Symptoms of anemia0 (none) 1 (somewhat) 2 (some) 3 (quite a lot) 4 (severe) (21) Free writing after the test

[0041] 5. Results As shown in Table 3, all subjects experienced a significant reduction in symptoms across multiple categories. Improvements were seen in both "physical symptoms" and "psychiatric symptoms." When the total PMS symptom scores for items (1) to (20) were added up, all three subjects' scores decreased after using the supplement compared to before using the supplement, with the total score improving by more than 40%.

[0042] Subject A: 27 → 16 → No data (No menstruation in the second cycle) (First cycle → First cycle → Second cycle) Subject B: 29 → 14 → 12 (First cycle → First cycle → Second cycle) Subject C: 21 → 12 → 10 (First cycle → First cycle → Second cycle)

[0043] More specifically, subject A's scores for "headache / heavy head feeling," "stiff shoulders," and "abdominal pain" were high before taking the supplement, but after the first supplement, all scores dropped to 0-1. The mental symptom of "irritability" also decreased significantly.

[0044] For subject B, the scores for "headache," "abdominal pain," "digestive symptoms," and "tearfulness" significantly decreased after taking the supplement, and remained stable at "0" or "1." The scores for the mental symptoms of "irritability" and "poor concentration" also significantly decreased after the second dose.

[0045] Before taking the supplements, subject C experienced moderate to severe symptoms such as "allergic symptoms," "stiff shoulders," and "dizziness," but after taking the supplements for the first and second cycles, all symptoms were reduced to a mild level of 0 to 1. According to self-reporting, the "dizziness" was an effect of the medication and was independent of the effects of the supplements.

[0046] Regarding item (21), Subject B responded that she felt a great effect on premenstrual symptoms and also felt an effect on menstrual symptoms. Subject C responded that she felt a slight effect on premenstrual symptoms and also felt a slight effect on menstrual symptoms.

[0047] From the above, it was suggested that taking Nannochloropsis supplements had an effect of alleviating PMS symptoms in all cases, and a clear trend of improvement was observed in "headache," "abdominal pain," and "mental disorders" in particular.

Claims

1. A composition containing Nannochloropsis for preventing and / or improving pre- and postmenstrual discomfort, or for preventing and / or improving menstrual-related diseases or symptoms.

2. The composition according to claim 1, which is a composition for preventing and / or improving menstrual-related diseases or symptoms, wherein the menstrual-related diseases or symptoms include at least one selected from the group consisting of adenomyosis, menstrual pain, menorrhagia, and anemia.

3. The composition according to claim 1, which is a composition for preventing and / or improving pre- and postmenstrual disorders.

4. The composition of claim 1 containing the Nannochloropsis powder.

5. The composition according to any one of claims 1 to 4, which is a food composition.

6. The composition according to any one of claims 1 to 4, which is a pharmaceutical composition.

7. Use of Nannochloropsis in the manufacture of a composition for preventing and / or ameliorating perimenopausal disorders or for preventing and / or ameliorating diseases or symptoms associated with menstruation.