Agent for ameliorating erectile dysfunction / agent for ameliorating male menopausal disorder

Abstract

[Problem] To propose a novel composition useful for ameliorating male menopausal disorder and / or erectile dysfunction. [Solution] An agent for ameliorating erectile dysfunction and / or an agent for ameliorating male menopausal disorder comprise a human stem cell supernatant liquid as an active ingredient. The agent for ameliorating erectile dysfunction and / or the agent for ameliorating male menopausal disorder are a cream to be used by being applied to a human body and comprise a human stem cell supernatant liquid as an active ingredient.

Description

Erectile dysfunction and male menopausal disorder treatment

[0001] The present invention relates to an agent for improving erectile dysfunction and / or male menopausal symptoms, which is useful for improving male erectile dysfunction and / or male menopausal symptoms.

[0002] Various proposals have been made in the past aimed at improving male erectile function and menopausal symptoms.

[0003] For example, Patent Document 1 proposes pharmaceuticals and foods containing one or more compounds selected from tangshenosides, lancemaside A, and syringin, which are said to suppress a decrease in blood testosterone levels and have an effect of improving various symptoms of male menopause.

[0004] Furthermore, Patent Document 2 proposes a composition for inhibiting phosphodiesterase 5 (PDE5) activity and a composition for improving erectile function, each of which contains a processed product of a plant of the genus Phyllanthus as an active ingredient.

[0005] JP 2006-306889 A JP 2022-7769 A

[0006] NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-90.Solomon H, et al. Heart 2003; 89: 251-253.Collinson P. Heart 2017; 103: 1231-1232.McCabe MP, et al. J Sex Med 2016; 13: 153-167.Kambou T, et al. Advances In Sexual Medicine 2014; 4:Diallo Y, et al. Open Journal of Urology 2015; 5: 147-154.Fatusi AO, et al. Aging Male 2003; 6: 79-85.Hatzichristou D, et al. J Sex Med 2005; 2: 751-758.Hattenhauer MG, et al. Am J Ophthalmol 1997; 123: 103-107.Khan AS, et al. Laryngoscope 2011; 121: 1049-1054.

[0007] Erectile dysfunction (hereinafter sometimes referred to as "ED" in this specification and drawings) affects approximately 40% of Japanese men aged 40 or older, and it is estimated that this proportion increases with age (Non-Patent Document 1). In addition, it is thought that ED has been on the rise in recent years (Non-Patent Document 2).

[0008] ED is thought to be caused by hormone deficiency, nerve damage, impaired blood flow to the penis, tissue damage, psychological factors, etc. (Non-Patent Document 3). Various factors are thought to be behind it, including lifestyle habits such as obesity and lack of exercise, lifestyle-related diseases such as diabetes and high blood pressure, and decreased testosterone levels (Non-Patent Documents 4 to 6).

[0009] Although lifestyle modification can be an effective intervention to improve erectile dysfunction (ED), there are currently limited effective measures to improve the age-related decline in testosterone and the resulting male menopausal symptoms (Non-Patent Documents 4 to 6). Male menopausal symptoms are thought to cause not only erectile dysfunction but also various other symptoms that impair the quality of life of middle-aged men, such as fatigue, mood changes, and decreased libido (Non-Patent Document 7).

[0010] Furthermore, ED treatments generally used in clinical practice are mainly limited to PDE5 inhibitors, etc., but PDE5 inhibitors have been reported to cause side effects ranging from mild headache and facial flushing to severe side effects such as anterior ischemic optic neuropathy and sudden hearing loss (Non-Patent Documents 8 to 10).

[0011] The object of the present invention is to propose a novel composition useful for improving erectile dysfunction and / or male menopausal symptoms.

[0012] While continuing their research into human stem cell supernatant, the inventors of the present application discovered that including human stem cell supernatant as an active ingredient is effective in improving erectile dysfunction and / or male menopausal symptoms.

[0013] The present invention can be exemplified as follows: [1] An agent for improving erectile dysfunction, comprising a human stem cell supernatant as an active ingredient.

[0014] [2] A drug for improving male menopausal symptoms containing human stem cell supernatant as an active ingredient.

[0015] [3] A drug for improving male menopause and erectile dysfunction containing human stem cell supernatant as an active ingredient.

[0016] [4] An erectile dysfunction treatment agent according to [1], which is a cream applied to the human body.

[0017] [5] A cream for use on the human body as described in [2] above to improve male menopausal symptoms.

[0018] [6] A cream for use on the human body to treat male menopause and erectile dysfunction as described in [3].

[0019] [7] The erectile dysfunction improving agent of [1] or [4], containing at least 10% by mass of human stem cell supernatant.

[0020] [8] The male menopausal disorder improving agent of [2] or [5], containing at least 10% by mass of human stem cell supernatant.

[0021] [9] A male menopausal disorder / erectile dysfunction improvement agent according to [3] or [6], containing at least 10% by mass of human stem cell supernatant.

[0022]

[10] The erectile dysfunction improving agent of [1] or [4], containing at least 5% by mass of liposome-processed human stem cell supernatant.

[0023]

[11] A male menopausal disorder improving agent according to [2] or [5], containing at least 5% by mass of liposome-processed human stem cell supernatant.

[0024]

[12] A male menopausal disorder / erectile dysfunction improvement agent according to [3] or [6], containing at least 5% by mass of liposome-processed human stem cell supernatant.

[0025] According to the present invention, a novel composition useful for improving erectile dysfunction and / or male menopausal symptoms can be provided.

[0026]

[0023] Figure 1 shows an example of a formulation for the erectile dysfunction improving agent, male menopausal disorder improving agent, and male menopausal disorder / erectile dysfunction improving agent of the present invention when provided in the form of a cream that is applied to the human body. Figure 2 shows changes in the erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Andropenic Menopause Index (AMS score) before and after use of a cream containing human stem cell supernatant (exosomes) of the present invention. Figure 3 shows changes in testosterone levels before and after use of a cream containing human stem cell supernatant (exosomes) of the present invention.

[0027] The agent for improving erectile dysfunction and / or the agent for improving male menopausal symptoms of this embodiment each contain human stem cell supernatant as an active ingredient.

[0028] Human stem cell supernatant is obtained by separating the culture medium that has been in direct or indirect contact with human stem cells after culturing the human stem cells for a predetermined period of time (e.g., several hours to several days) from the human stem cells. It can also be produced by a method such as the "Method for Producing Stem Cell Culture Supernatant" disclosed in Japanese Patent No. 6958350. Commercially available human stem cell supernatant can also be used in the present invention.

[0029] According to the investigations of the present inventors, a composition containing human stem cell supernatant as a compounded ingredient was found to have an effect of improving erectile dysfunction and male menopausal symptoms.

[0030] Erectile dysfunction is one type of male menopausal disorder. Research by the present inventors has shown that a composition containing human stem cell supernatant as a compounding ingredient not only acts as an erectile dysfunction improver, but also has the effect of improving male menopausal disorders, and improving male menopausal disorders and erectile dysfunction.

[0031] The agent for improving erectile dysfunction, the agent for improving male menopause, and the agent for improving male menopause and erectile dysfunction, which contain the human stem cell supernatant of this embodiment as an active ingredient, can be provided in various forms, such as food, cosmetics, and pharmaceuticals. In the case of food, it can be provided as a food or drink in various forms and styles as long as it is edible. In the case of cosmetics and pharmaceuticals, it can be provided in various forms and styles, such as creams and ointments to be applied to the human body, forms to be sprayed on the human body, and forms to be attached to the human body.

[0032] Regardless of the form in which it is provided, various ingredients that are traditionally added to foods, cosmetics, and pharmaceuticals can be added to produce an erectile dysfunction improvement agent and / or an erectile dysfunction improvement agent containing human stem cell supernatant as an active ingredient in various forms such as foods, cosmetics, and pharmaceuticals, as long as the effect of improving erectile dysfunction and / or improving male menopausal symptoms that is exerted by the inclusion of human stem cell supernatant in the formulation ingredients is not impaired.

[0033] As one of the various embodiments described above, the erectile dysfunction improving agent and / or male menopausal disorder improving agent of the present invention containing human stem cell supernatant as an active ingredient can be provided as a cream to be applied to the human body.

[0034] In this case, too, various ingredients that have traditionally been incorporated into creams that are applied to the human body can be incorporated, within a range that does not impair the erectile dysfunction improvement effect and / or male menopausal disorder improvement effect exerted by the inclusion of human stem cell supernatant as a compounding ingredient, to provide an erectile dysfunction improvement agent and / or male menopausal disorder improvement agent that contains human stem cell supernatant as an active ingredient as a cream that is applied to the human body.

[0035] In this case, a cream for application to the human body containing the human stem cell supernatant of the present invention as an active ingredient can be provided as an erectile dysfunction improving agent and / or male menopausal disorder improving agent, using a conventionally known method for producing a skin cream, such as adding and blending human stem cell supernatant with conventionally known ingredients and water used in the production of a skin cream for application to the human body, mixing them, and emulsifying the ingredients by stirring using a homomixer or the like.

[0036] An example of the formulation of the agent for improving erectile dysfunction and / or the agent for improving male menopausal disorder of this embodiment in the form of a cream to be applied to the human body is shown in Figure 1. The amounts of the ingredients in Figure 1 are expressed in mass %.

[0037] In the formulation examples shown in Figure 1, human adipose-derived stem cell conditioned medium, human dental pulp cell conditioned medium, and human uterine mesenchymal stem cell exosomes are human stem cell supernatants.

[0038] The human stem cell supernatant fluid described above can be liposome-processed to facilitate absorption by the human body, or non-liposome-processed human stem cell supernatant fluid can also be used.

[0039] When using human stem cell supernatant fluid that has not been liposome-processed, the agent can be an agent for improving erectile dysfunction and / or an agent for improving male menopausal symptoms, containing at least 10% by mass of human stem cell supernatant fluid.

[0040] When liposome-processed human stem cell supernatant is used, the agent for improving erectile dysfunction and / or male menopausal symptoms can be formulated with liposome-processed human stem cell supernatant at a concentration of at least 5% by mass.

[0041] According to the research conducted by the present inventors, when using human stem cell supernatant fluid that has not been liposome-processed, it has been found that the above-mentioned effect of improving erectile dysfunction can be achieved by incorporating human stem cell supernatant fluid at a concentration of at least 10% by mass.

[0042] Furthermore, when liposome-processed human stem cell supernatant is used, it has been found that the above-mentioned erectile dysfunction improving effect can be achieved by incorporating at least 5% by mass of human stem cell supernatant.

[0043] Examples of the present invention will be described below, but the present invention is not limited to the above-mentioned embodiments or the examples described below, and can be modified in various ways within the technical scope understood from the claims.

[0044] The cream of this example (cream containing human stem cell supernatant) was prepared according to the formulation shown in FIG. 1 using a conventional method for producing a cream to be applied to the human body.

[0045] The prepared human stem cell supernatant-containing cream contains 20% culture supernatant of various human stem cells collected from healthy Japanese individuals, which were cultured within 24 or 36 hours. As shown in Table 1, this cream also contains 3.50 x 10 １０ It has been confirmed that the dental pulp contains more than 1000 exosomes per mL, and that the main components are growth factors such as β-NGF, VEGF, HGF, TGF-β, and EGF.

[0046] The clinical efficacy of the prepared cream containing human stem cell supernatant in treating erectile dysfunction and male menopausal disorders was evaluated as follows.

[0047] The subjects were men in their late 30s to 60s with no underlying diseases and an Aging Male's Symptoms score (AMS score) of approximately 40 or above who had concerns or symptoms of male menopause (LOH syndrome), and men in their 40s to 60s with no underlying diseases and an International Index of Erectile Function-5 (IIEF-5) score of approximately 16 or below.

[0048] The subjects were asked to apply the human stem cell supernatant cream prepared as described above to the genitals and scrotum twice daily, and the erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Males' Symptoms score (AMS score) were evaluated before and 30 days after use, and the results were compared using a paired t-test. Qualitative opinions after use were also collected.

[0049] The ages and other details of the 10 subjects are as shown in Table 2 below.

[0050] The results of the clinical efficacy evaluation are shown in Table 3.

[0051] As shown in Table 3 above, after use of the cream, significant improvements were observed in EHS (2.3±0.7 → 3.3±0.7, P<0.001), IIEF-5 (11.3±4.6 → 16.4±5.5, P<0.001), and AMS score (45.7±6.6 → 36.4±6.2, P<0.001) compared to before use.

[0052] Qualitative comments included, "I have more morning erections," "I can now maintain an erection during sexual intercourse," and "I feel less tired after work."

[0053] Use of the cream containing human stem cell supernatant prepared as described above resulted in improvements in EHS, IIEF-5 score, and AMS score.

[0054] From this, it was recognized that a composition containing human stem cell supernatant as an active ingredient is useful for improving erectile dysfunction and / or male menopausal symptoms.

[0055] Human stem cell supernatant contains vascular endothelial growth factor and other factors, which may have contributed to the improvement of erectile dysfunction by improving the function of vascular endothelial cells in the corpus cavernosum.

[0056] The cream containing the human stem cell supernatant prepared in Example 1 was used to evaluate changes in testosterone levels and other factors before and after use of the cream in the 10 subjects from Example 1, as follows.

[0057] Each of the 10 subjects applied a cream containing human stem cell supernatant (exosomes) to the genitals and scrotum twice daily, and various scores were evaluated before and 30 days after use. Qualitative interviews were also conducted regarding subjective feelings before and after use. Blood testosterone levels were measured before and after use using the WELLMILL Saliva Testosterone + Cortisol Test Kit for Male Menopause (https: / / shop.well-mill.com / shop / 104).

[0058] The evaluation items were as follows: - Erection Hardness Score (EHS) - International Index of Erectile Function-5 (IIEF-5) - Andropause Index (AMS score) - Evaluation of subject's self-awareness (free-form questionnaire) - Changes in testosterone levels before and after cream use Analysis method: Various scores were compared before and after use of the cream containing human stem cell supernatant (exosomes), and paired t-tests and chi-squared tests were performed.

[0059] The changes in erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Andropause Index (AMS score) are shown in Figure 2, and the changes in testosterone levels before and after using the cream are shown in Figure 3.

[0060] As a result, use of the cream containing human stem cell supernatant resulted in improvements in erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5) score, and Aging Males' Symptoms score (AMS score), as shown in Figure 2. Furthermore, as shown in Figure 3, an increase in testosterone levels was observed before and after use of the cream.

[0061] According to interviews about subjective states before and after use, improvements were observed in subjective fatigue, decreased libido, and satisfaction during sexual intercourse.

[0062] As shown in Table 1, human stem cell supernatant is rich in various cytokines, including growth factors (EGF, VEGF, etc.).

[0063] Vascular endothelial cells have the ability to produce various physiologically active substances, such as nitric oxide (NO), which contributes to vasodilation. It is possible that the cytokines contained in the cream containing human stem cell supernatant (exosomes) may improve the function of these vascular endothelial cells, promoting blood flow to the penis and contributing to the improvement of ED.

[0064] It is also predicted that human stem cell supernatant contributes to the improvement of ED through various mechanisms, such as angiogenesis in the penis, improved erectile sensation through nerve repair, and anti-inflammatory effects of the corpus cavernosum tissue.

[0065] Subjective symptom assessment revealed an improvement in male menopausal symptoms, which is thought to be closely related to increased testosterone levels. Human stem cell supernatant may have contributed to improving not only penile function, but also testicular function through increased blood flow and nerve repair.

Claims

1. An agent for improving erectile dysfunction containing human stem cell supernatant as an active ingredient.

2. A drug for improving male menopausal symptoms that contains human stem cell supernatant as an active ingredient.

3. A drug for improving male menopause and erectile dysfunction that contains human stem cell supernatant as an active ingredient.

4. The erectile dysfunction improving agent according to claim 1, which is in the form of a cream that is applied to the human body.

5. The agent for improving male menopausal symptoms according to claim 2, which is a cream to be applied to the human body.

6. The agent for improving male menopausal disorders and erectile dysfunction according to claim 3, which is a cream that is applied to the human body.

7. An erectile dysfunction improving agent according to claim 1 or 4, containing at least 10% by mass of human stem cell supernatant.

8. A male menopausal disorder amelioration agent according to claim 2 or 5, containing at least 10% by mass of human stem cell supernatant.

9. A drug for improving male menopausal disorders and erectile dysfunction according to claim 3 or 6, containing at least 10% by mass of human stem cell supernatant.

10. An erectile dysfunction improving agent according to claim 1 or 4, containing at least 5% by mass of liposome-processed human stem cell supernatant.

11. A drug for improving male menopausal symptoms according to claim 2 or 5, containing at least 5% by mass of liposome-processed human stem cell supernatant.

12. A drug for improving male menopausal disorders and erectile dysfunction according to claim 3 or 6, containing at least 5% by mass of liposome-processed human stem cell supernatant.

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