Composition for improving sexual function comprising salvia miltiorrhiza extract as active ingredient

Abstract

The present invention relates to a pharmaceutical composition for improving sexual function, comprising a Salvia miltiorrhiza extract as an active ingredient. Specifically, the pharmaceutical composition can improve overall sexual satisfaction through the improvement of one or more selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

Description

A composition for improving sexual function containing Salvia miltiorrhiza extract as an active ingredient

[0001] The present invention relates to a composition for improving sexual function comprising Salvia miltiorrhiza extract as an active ingredient.

[0002] Sexual dysfunction, sexual malfunction, or sexual disorder is a condition characterized by difficulty in normal sexual activity (including physical pleasure, sexual desire, preferences, sexual arousal, and orgasm). While sexual dysfunction was previously considered to be caused by psychogenic impotence, advancements in medicine have revealed that more than 50% of patients with sexual dysfunction suffer from organic impotence rather than psychogenic causes, such as diseases of the vascular, nervous, and endocrine systems, diabetes, hypertension, and medication use.

[0003] In men, male sexual dysfunction can be broadly classified into erectile dysfunction, characterized by the inability to achieve or / or maintain an erection necessary for sexual activity, and sexual neurasthenia, which results from the loss of ejaculatory control. Erectile dysfunction generally refers to erectile dysfunction (inability to achieve an erection), priapism (persistent and painful penile erection), and disorders of the penile cavernous tissue and related fascia. Erectile dysfunction is largely caused by psychogenic and organic factors, with organic causes accounting for 70–80% of cases; organic causes include neurogenic, vascular, and endocrine factors. This decline in sexual function is closely related to a decrease in the body's physiological functions and, in severe cases, can develop into chronic erectile dysfunction. Furthermore, sexual neurasthenia, typified by premature ejaculation, is known to manifest as a loss of sexual control resulting from the disruption of the balance between the peripheral and central nervous systems and the failure to maintain a smooth cooperative system.

[0004] Treatment for sexual dysfunction often involves the replacement of sex hormones, and injectables containing Carverjet are FDA-approved treatments that can be administered via self-injection. Alternatively, a vacuum erection device can be used to induce an erection and maintain it by wrapping a rubber band around the base of the penis to block blood flow, or penile vascular reconstruction surgery can be performed to reconstruct blood vessels when they are blocked due to injury or disease. Inflatable or non-inflatable penile implants may also be inserted.

[0005] Sexual function enhancers using natural products have also been used since ancient times, and the use of such naturally derived drugs can provide a broader approach to disease treatment with fewer side effects. Accordingly, the sexual function-improving activity of various plant extracts is being investigated.

[0006] Meanwhile, Salvia miltiorrhiza (SM) is a medicinal herb that has been widely used in traditional Korean medicine since ancient times. It is a perennial plant belonging to the order Lamiales and the family Lamiaceae, and its origin is China. Cryptotanshinone, tanshinone I, tanshinone IIA, tanshinone IIB, dihydrotanshinone, salvianolic acid B, methyl tanshinonate, methylene tanshinquinone, beta-sitosterol, hydroxytanshinone, neotanshinone, salviol, isocryptotanshinone, miltirone, tanshinol I, tanshinol II, and vitamin E have been reported as components contained in the roots of Salvia miltirone. Furthermore, Salvia miltiorrhiza has been reported to possess various efficacies, including protection against ischemic injury, coronary artery relaxation, inhibition of atherosclerosis, antihypertensive, antihyperlipidemic, antidiabetic, antibacterial, antioxidant, anticancer, antimutagenic, and antithrombotic effects. In vitro experiments have revealed that this extract can inhibit the proliferation of prostate cancer cell lines and reduce prostate size and improve other indicators of prostate health in a BPH mouse model. While research is ongoing regarding the diverse applications of Salvia miltiorrhiza extract, there is currently no research available regarding its use in improving sexual function.

[0007] The objective of the present invention is to provide a composition for improving sexual function comprising Salvia miltiorrhiza extract as an active ingredient.

[0008] The present invention provides a composition for improving sexual function characterized by containing Salvia miltiorrhiza extract as an active ingredient.

[0009] The above Salvia miltiorrhiza extract may be a distilled water or ethanol extract, and other solvents may also be used. Depending on the type of extraction solvent, the extraction temperature, extraction time, amount of solvent, and method of treating residual components may be designed differently. Various solvents may also be used for extraction, and extractable solvents include water, ethanol, methanol, fatty oil, glycerin, horse oil, ethyl acetate, acetone, butanol, isopropanol, methylene chloride, and supercritical carbon dioxide.

[0010] The above Salvia miltiorrhiza extract may be an extract obtained particularly with an alcohol having 1 to 6 carbon atoms or a mixed solvent thereof. The alcohol may be ethanol, and may be 40 to 99% ethanol. Preferably, the Salvia miltiorrhiza extract of the present invention is an aqueous alcohol extract.

[0011] The above Salvia miltiorrhiza extract can be concentrated. Additionally, moisture can be removed by heating the extract at 40 to 80°C using a microwave drying method. Alternatively, the extract can be concentrated and dried using a low-temperature vacuum drying method. Low-temperature vacuum drying is a drying method in which the pressure inside the dryer is maintained at a vacuum and the temperature is controlled to approximately 5 to 15°C, which prevents denaturation of the extract components and ensures that the taste and aroma are not lost. Depending on the design conditions, methods such as spray drying, cold air drying, hot air drying, freeze drying, far-infrared drying, shade drying, and vacuum drying may also be used.

[0012] The above Salvia miltiorrhiza concentrate can be dried to produce various formulations. The extract can be concentrated and dried using a spray drying method and then prepared into various formulations. For example, it can be prepared as a powder. Low-temperature vacuum drying is a drying method in which the pressure inside the dryer is maintained at a vacuum and the temperature is controlled to approximately 5 to 15°C; this method prevents denaturation of the extract components and ensures that the taste and aroma are not lost. Depending on the design conditions, methods such as cold air drying, hot air drying, freeze-drying, far-infrared drying, shade drying, and reduced-pressure drying may also be used. Preferably, Salvia miltiorrhiza can be eluted with 50 L of ethanol for 24 hours and then concentrated under reduced pressure. To this, 1500 mL of water is added, and equal amounts of n-hexane, dichloromethane (CH2Cl2), and ethyl acetate (EtOAc) are added in sequence and extracted twice to produce a red extract in a gel state.

[0013] The above pharmaceutical composition may include a carrier or an excipient, and each of the above may be added in an amount preferably from 0.001% to 90% by weight, more preferably from 0.001% to 50% by weight, and most preferably from 0.001% to 30% by weight based on the total weight of the pharmaceutical composition.

[0014] The appropriate dosage of the above pharmaceutical composition can be prescribed in various ways depending on factors such as the formulation method, mode of administration, patient's age, body weight, sex, pathological condition, food, time of administration, route of administration, excretion rate, and response sensitivity. The pharmaceutical composition of the present invention contains the above tanshinone derivatives as active ingredients. The above pharmaceutical composition can be administered orally or parenterally during clinical administration and can be used in the form of a general pharmaceutical formulation. That is, the composition of the present invention can be administered in various oral and parenteral formulations during actual clinical administration; when formulated, it is prepared using diluents or excipients such as commonly used fillers, volume expanders, binders, humectants, disintegrants, and surfactants. Solid formulations for oral administration include tablets, pills, powders, granules, and capsules, and these solid formulations are prepared by mixing at least one or more excipients, such as starch, calcium carbonate, sucrose, lactose, and gelatin, with the tanshinone derivatives. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid formulations for oral administration include suspensions, oral liquids, emulsions, and syrups; in addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as humectants, sweeteners, flavorings, and preservatives, may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspension solvents. Witepsol, macrogol, Tween 61, cocoa paste, laurin paste, glycerol, and gelatin may be used as bases for suppositories.

[0015] The dosing unit may contain, for example, 1, 2, 3, or 4 times the individual dose, or 1 / 2, 1 / 3, or 1 / 4 times. The individual dose preferably contains an amount of the active drug administered in a single dose, which corresponds to the entire, 1 / 2, 1 / 3, or 1 / 4 of the usual daily dose. The effective dose of tanshinones (Tanshinone I, Tanshinone IIA, Cryptotanshinone, 15,16-Dihydrotanshinone, Tanshinoic acid, etc.) is concentration-dependent but preferably 0.1 mg to 1,000 mg / kg, more preferably 0.4 to 500 mg / kg, and may be administered 1 to 6 times a day. Accordingly, it may be administered in the range of 0.1 to 6,000 mg / day per kg of adult body weight.

[0016] The above pharmaceutical composition may be administered to mammals, such as rats, livestock, and humans, via various routes. Any mode of administration is expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater, or intracerebrovascular injection.

[0017] In the present invention, the improvement of sexual function is one or more improvements selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

[0018] The present invention provides a health functional food for improving sexual function characterized by comprising a Salvia miltiorrhiza extract as an active ingredient. The Salvia miltiorrhiza extract may be an extract obtained by extracting Salvia miltiorrhiza (Salvia miltiorrhiza Bunge) with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.

[0019] The Salvia miltiorrhiza extract of the present invention may be added in an amount of preferably 0.001% to 50% by weight, more preferably 0.001% to 40% by weight, and most preferably 0.001% to 10% by weight, based on the total weight of the health functional food.

[0020] The above-mentioned health functional foods include forms such as tablets, capsules, pills, granules, oral films, or liquids, and foods to which the extract of the present invention may be added include, for example, meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, powdered milk, health food, raw food, fermented milk, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes. Specifically, health foods containing Salvia miltiorrhiza extract may include health foods and confectionery such as juices, teas, jellies, and juices made with Salvia miltiorrhiza extract as the main ingredient, as well as folk remedies intended for edema, nephritis, urethritis, etc.

[0021] The present invention provides a method for improving sexual function in a subject with reduced sexual function, wherein the method comprises administering a therapeutically effective amount of Salvia miltiorrhiza extract to the subject.

[0022] The above Salvia miltiorrhiza extract may be obtained by extracting Salvia miltiorrhiza Bunge with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.

[0023] The above improvement of sexual function may be one or more selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

[0024] The present invention relates to a composition for improving sexual function comprising Salvia miltiorrhiza extract as an active ingredient, and specifically, can improve overall sexual satisfaction through one or more improvements selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

[0025] Figure 1 is a schematic diagram of the human application plan for a clinical trial to improve sexual function using Salvia miltiorrhiza extract.

[0026] Figure 2 is a graph showing the change in the total IIEF score at 0 and 12 weeks when the Salvia miltiorrhiza extract according to the present invention is applied to the human body.

[0027] Preferred embodiments of the present invention are described in detail below. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms, and the contents introduced herein are provided to sufficiently convey the concept of the present invention.

[0028] <Example 1. Preparation of Salvia miltiorrhiza extract (SAGX)>

[0029] After crushing the roots of *Salvia miltiorrhiza*, they were extracted with a 40–99% ethanol aqueous solution at 30–80°C. The process of extracting in the ethanol aqueous solution for 2 to 24 hours and, if necessary, extracting again in fresh ethanol for 2 to 12 hours was repeated 2 to 5 times to collect the extracts, which were then centrifuged to obtain the supernatant. Subsequently, the obtained supernatant was collected, evaporated and dried at 30–75°C, ground, and filtered through a mesh of 80 or larger to prepare the *Salvia miltiorrhiza* extract (SAGX).

[0030]

[0031] <Example 2. Clinical Trial on Improvement of Sexual Function with Salvia miltiorrhiza Extract>

[0032] The clinical trial participants were 74 adult males aged 40 to 80 years, and a schematic diagram of the human application plan for this clinical trial is shown in Figure 1.

[0033]

[0034] Participants were randomly assigned to a test group (N=40) and a control group (N=34). For 12 weeks, the test group consumed a test food containing Salvia miltiorrhiza extract once a day, taking 2 capsules with water after breakfast (400 mg / day of Salvia miltiorrhiza extract), while the control group (Placebo) consumed it in the same manner as the test food.

[0035] From December 8, 2021, to March 10, 2023, the International Index of Erectile Function (IIEF) was measured using the International Index of Erectile Function Questionnaire during four visits, including a screening visit. The aforementioned International Index of Erectile Function Questionnaire consisted of 15 items across five domains, including erectile ability, orgasmic ability, sexual desire, sexual intercourse satisfaction, and overall sexual satisfaction, and the scores of each item were aggregated and analyzed according to the purpose of the analysis.

[0036] The change in the total IIEF score is shown in Table 1 and Figure 2 below.

[0037] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 31.80±20.18 30.44±19.22 1 After 2 weeks 41.15±21.84 27.09±18.78 Change from baseline 9.35±13.64 -3.35±19.96 0.000 2 Data are expressed as mean ± standard deviation

[0038] As shown in Table 1 and Figure 2, in the analysis of changes in the total score of the International Index of Erectile Function (IIEF), after 12 weeks of intake, the test group increased by 9.35±13.64 points (p<0.0001), while the control group decreased by 3.35±19.96 points (p=0.3344), showing a statistically significant difference between the two groups (p=0.0002). The results of the analysis of changes in erectile function among the IIEF sub-items are shown in Table 2. In the analysis of changes in erectile function, after 12 weeks of intake, the test group increased by 5.20±7.50 points (p<0.0001), while the control group decreased by 1.56±10.89 points (p=0.4098), showing a statistically significant difference between the two groups (p=0.0006).

[0039] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 12.00±10.14 11.82±9.83 12 weeks after 17.20±11.22 10.26±9.76 Change from baseline 5.20±7.50 -1.56±10.89 0.0006 Data are expressed as mean ± standard deviation

[0040]

[0041] The results of the analysis of changes in sexual pleasure among the IIEF sub-items are shown in Table 3. In the analysis of changes in sexual pleasure, after 12 weeks of intake, the test group increased by 1.70±3.05 points (p=0.0011), and the control group decreased by 0.47±4.05 points (p=0.5025), and a statistically significant difference was found between the two groups (p=0.0034).

[0042] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 3.85±3.99 3.47±3.651 After 2 weeks 5.55±4.27 3.00±3.68 Change from baseline 1.70±3.05 -0.47±4.05 0.0034 Data are expressed as mean ± standard deviation

[0043]

[0044] The results of the analysis of changes in sexual desire among the IIEF sub-items are shown in Table 4. In the analysis of changes in sexual desire, after 12 weeks of intake, the test group increased by 0.38±1.66 points (p=0.1609), and the control group decreased by 0.35±1.39 points (p=0.1482), and a statistically significant difference was found between the two groups (p=0.0351).

[0045] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 6.30±1.68 6.09±1.601 After 2 weeks 6.68±1.89 5.74±1.52 Change from baseline 0.38±1.66 -0.35±1.39 0.0351 Data are expressed as mean ± standard deviation

[0046]

[0047] The results of the analysis of changes in sexual satisfaction among the IIEF sub-items are shown in Table 5. In the analysis of changes in sexual satisfaction, after 12 weeks of intake, the test group increased by 1.50±2.86 points (p=0.0019), while the control group decreased by 0.82±4.27 points (p=0.2694), and a statistically significant difference was found between the two groups (p=0.0050).

[0048] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 4.08±4.23 3.88±3.96 After 2 weeks 5.58±4.19 3.06±3.70 Change from baseline 1.50±2.86 -0.82±4.27 0.00 Data are expressed as mean ± standard deviation

[0049]

[0050] The results of the analysis of changes in overall sexual satisfaction are shown in Table 6. In the analysis of changes in overall sexual satisfaction, after 12 weeks of intake, the test group increased by 0.58±1.26 points (p=0.0063), and the control group decreased by 0.15±1.42 points (p=0.5492), showing a statistically significant difference between the two groups (p=0.0304).

[0051] Test group (N=40) Control group (N=34) p-value Baseline (0 weeks) 5.58±1.66 5.18±1.731 After 2 weeks 6.15±1.56 5.03±1.66 Change from baseline 0.58±1.26 -0.15±1.42 0.0304 Data are expressed as mean ± standard deviation

[0052]

[0053] As shown in the results above, it was confirmed that the Salvia miltiorrhiza extract of the present invention significantly improves sexual function and improves overall sexual satisfaction.

[0054]

[0055] <Formulation Example 1. Pharmaceutical Formulation>

[0056] Formulation Example 1-1. Preparation of Tablets

[0057] 400 mg of the Salvia miltiorrhiza extract of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silica. A 10% gelatin solution was added to this mixture, and the mixture was ground and passed through a 14-mesh sieve. This was dried, and the mixture obtained by adding 160 g of potato starch, 50 g of active ingredient, and 5 g of magnesium stearate was made into tablets.

[0058] Formulation Example 1-2. Preparation of Injectable Solution

[0059] 100 mg of the Salvia miltiorrhiza extract of the present invention, 0.6 g of sodium chloride, and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20°C for 30 minutes.

[0060] <Preparation Example 2. Preparation of a Health Functional Food>

[0061] Preparation Example 2-1. Preparation of a health functional food

[0062] The present invention was prepared by mixing 400 mg of Salvia miltiorrhiza extract, an appropriate amount of a vitamin mixture, 70 μg of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B1, 0.15 mg of vitamin B2, 0.5 mg of vitamin B6, 0.2 μg of vitamin B12, 10 mg of vitamin C, 10 μg of biotin, 1.7 mg of nicotinamide, 50 μg of folic acid, 0.5 mg of calcium pantothenate, an appropriate amount of a mineral mixture, 1.75 mg of ferrous sulfate, 0.82 mg of zinc oxide, 25.3 mg of magnesium carbonate, 15 mg of monopotassium phosphate, 55 mg of disodium phosphate, 90 mg of potassium citrate, 100 mg of calcium carbonate, and 24.8 mg of magnesium chloride to form granules, but it can be prepared by modifying it into various formulations depending on the use. In addition, the composition ratio of the above vitamin and mineral mixture may be arbitrarily modified, and the above ingredients may be mixed and manufactured according to a conventional method for manufacturing health functional foods.

[0063] Preparation Example 2-2. Preparation of a health functional beverage

[0064] 400 mg of the Salvia miltiorrhiza extract of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water were mixed and a beverage was prepared by stirring, heating, filtering, sterilizing, and refrigerating according to a conventional beverage preparation method.

Claims

1. A composition for improving sexual function characterized by containing Salvia miltiorrhiza extract as an active ingredient.

2. In Paragraph 1, A composition for improving sexual function, characterized in that the above-mentioned Salvia miltiorrhiza extract comprises an extract of Salvia miltiorrhiza Bunge obtained by extracting it with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.

3. In Paragraph 1, A composition for improving sexual function, characterized in that the above-mentioned improvement of sexual function is one or more selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

4. A health functional food for improving sexual function characterized by containing Salvia miltiorrhiza extract as an active ingredient.

5. In Paragraph 4, A health functional food for improving sexual function, characterized in that the above-mentioned Salvia miltiorrhiza extract comprises an extract of Salvia miltiorrhiza Bunge obtained with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.

6. In Paragraph 4, The above health functional food is a health functional food for improving sexual function, characterized in that it is a tablet, capsule, pill, granule, oral film, or liquid.

7. As a method to improve sexual function in subjects with reduced sexual function, The above method is characterized by including administering a therapeutically effective amount of Salvia miltiorrhiza extract to a subject.

8. In Paragraph 7, A method characterized by obtaining the above-mentioned Salvia miltiorrhiza extract by extracting Salvia miltiorrhiza Bunge with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.

9. In Paragraph 7, The above method is characterized by improving one or more selected from the group consisting of erectile function, sexual pleasure, sexual desire, and sexual intercourse satisfaction.

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