SYNERGISTIC HERBAL COMPOSITION FOR SEXUAL DISORDERS

Abstract

The invention disclosed herein is a synergistic herbal composition comprising extracts of Mucuna pruriens, Cynara cardunculus, Trigonella foenum graecum, Withania somnifera and L-arginine along with pharmaceutically acceptable excipients, having libido enhancing, testosterone levels increasing and ejaculation delaying properties. The present invention also disclosed herein a process for preparation of said composition.

Claims

1. An herbal composition comprising an extract of Mucunapruriens, an extract of Cynara cardunculus, an extract of Trigonella foenum graecum, an extract of Withania somnifera, L-arginine, and a pharmaceutically acceptable excipient, wherein the herbal composition meets at least one of the following conditions: the extract of Mucuna pruriens and at least one of the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, and the extract of Withania somnifera are present in the herbal composition in a first ratio of 1:2 by weight; and the extract of Cynara cardunculus and at least one of the extract of Trigonella foenum graecum, and the extract of Withania somnifera are present in the herbal composition in a second ratio of 1:1 by weight.

2. The herbal composition as claimed in claim 1, wherein the extract of Mucuna pruriens and the extract of Cynara cardunculus are present in the herbal composition in the first ratio of 1:2 by weight.

3. The herbal composition as claimed in claim 2, wherein the extract of Mucuna pruriens and at least one of the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in the first ratio of 1:2 by weight.

4. The herbal composition as claimed in claim 1, wherein the extract of Mucuna pruriens and the extract of Trigonella foenum graecum are present in the herbal composition in the first ratio of 1:2 by weight.

5. The herbal composition as claimed in claim 1, wherein the extract of Mucuna pruriens and the extract of Withania somnifera are present in the herbal composition in the first ratio of 1:2 by weight.

6. The herbal composition as claimed in claim 1, wherein the extract of Cynara cardunculus and the extract of Trigonella foenum graecum are present in the herbal composition in the second ratio of 1:1 by weight.

7. The herbal composition as claimed in claim 1, wherein the extract of Cynara cardunculus and the extract of Withania somnifera are present in the herbal composition in the second ratio of 1:1 by weight.

8. The herbal composition as claimed in claim 1, wherein the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in the second ratio of 1:1 by weight.

9. An herbal composition, wherein said composition is a dosage form, said dosage form comprising: a) an extract of Mucuna pruriens in an amount of 40 to 80 mg; b) an extract of Cynara cardunculus in an amount of 90 to 150 mg; c) an extract of Trigonella foenum graecum in an amount of 90 to 150 mg; d) an extract of Withania somnifera in an amount of 90 to 150 mg; e) L-arginine in an amount of 40 to 80 mg; and f) a pharmaceutically acceptable excipient.

10. The herbal composition as claimed in claim 9, wherein said dosage form comprises: a) the extract of Mucuna pruriens in an amount of 50 to 72 mg; b) the extract of Cynara cardunculus in an amount of 100 to 144 mg; c) the extract of Trigonella foenum graecum in an amount of 100 to 144 mg; d) the extract of Withania somnifera in an amount of 100 to 144 mg; and e) L-arginine in an amount of 50 to 72 mg.

11. The herbal composition as claimed in claim 9, wherein said dosage form comprises: a) the extract of Mucuna pruriens in an amount of 50 mg; b) the extract of Cynara cardunculus in an amount of 100 mg; c) the extract of Trigonella foenum graecum in an amount of 100 mg; d) the extract of Withania somnifera in an amount of 100 mg; and e) L-arginine in an amount of 50 mg.

12. The herbal composition as claimed in claim 9, wherein said pharmaceutically acceptable excipient is selected from the group consisting of binders, glidants, lubricants, diluents, disintegrants, emulsifying agents, anti-caking agents, anti-adherents, granulating agents, flavors and mixtures thereof.

13. The herbal composition as claimed in claim 12, wherein said pharmaceutically acceptable excipient comprises a mixture of 40 to 70 mg Microcrystalline Cellulose and 4 to 8 mg Silicon dioxide.

14. The herbal composition as claimed in claim 9, wherein said pharmaceutically acceptable excipient is present in the dosage form in an amount of 40 mg to 100 mg.

15. The herbal composition as claimed in claim 9, wherein said dosage form is selected from the group consisting of tablets, capsules, granules, and pills.

16. A process for preparation of an herbal composition as claimed in claim 1, comprising; a) sieving and weighing the extract of Mucuna pruriens, the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, the extract of Withania somnifera, and L-Arginine; b) after the step of sieving and weighing, blending the extract of Mucuna pruriens, the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, the extract of Withania somnifera, and L-Arginine for 5 minutes at 25 rpm to produce a blended mixture; c) adding the pharmaceutically acceptable excipient to the blended mixture, followed by blending for 10 minutes at 25 rpm to obtain a homogenized mixture; and d) filling the homogenized mixture into a capsule shell to obtain the dosage form.

17. A process for preparation of an herbal composition as claimed in claim 9, comprising; a) sieving and weighing the extract of Mucuna pruriens, the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, the extract of Withania somnifera, and L-Arginine; b) after the step of sieving and weighing, blending the extract of Mucuna pruriens, the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, the extract of Withania somnifera, and L-Arginine for 5 minutes at 25 rpm to produce a blended mixture; c) adding the pharmaceutically acceptable excipient to the blended mixture, followed by blending for 10 minutes at 25 rpm to obtain a homogenized mixture; and d) filling the homogenized mixture into a capsule shell to obtain the dosage form.

18. A method of treating a sexual disorder by at least one of increasing testosterone levels, enhancing erection, reducing anxiety, and delaying ejaculation, comprising administering an herbal composition as claimed in claim 1 to a subject in need thereof.

19. A method of treating a sexual disorder by at least one of increasing testosterone levels, enhancing erection, reducing anxiety, and delaying ejaculation, comprising administering an herbal composition as claimed in claim 9 to a subject in need thereof.

20. An herbal composition comprising an extract of Mucuna pruriens, an extract of Cynara cardunculus, an extract of Trigonella foenum graecum, an extract of Withania somnifera, L-arginine, and a pharmaceutically acceptable excipient, wherein the herbal composition meets at least one of the following conditions: L-arginine and the extract of Mucuna pruriens are present in a third ratio of 1:1 by weight; and L-arginine and at least one of the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, and the extract of Withania somnifera are present in the herbal composition in a fourth ratio of 1:2 by weight.

21. An herbal composition comprising: a first extract selected from the group consisting of an extract of Mucuna pruriens, an extract of Rhodiola Rosea, an extract of horny goat weed, an extract of Asparagus racemosus, an extract of Hypericum peoratum, an extract of Butea Superba, an extract of Griffonia simplicifolia, an extract of Muira Puma, an extract of Damiana, and a mixture thereof; an extract of Cynara cardunculus, an extract of Trigonella foenum graecum, an extract of Withania somnifera, L-arginine, and a pharmaceutically acceptable excipient, wherein: the extract of Cynara cardunculus and at least one of the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in a second ratio of 1:1 by weight; the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in the second ratio of 1:1 by weight; and/or the first extract and at least one of the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, and the extract of Withania somnifera are present in the herbal composition in a first ratio of 1:2 by weight.

Description

BRIEF DESCRIPTION OF FIGURE

[0075] FIG. 1: Mean change from baseline in IELT subscale score at the end of the treatment

[0076] FIG. 2: Mean change from baseline in PEP subscale score at the end of the treatment

DETAILED DESCRIPTION OF THE INVENTION

[0077] The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

[0078] Source and Geographical Origin of the Biological Material Used in the Invention:

[0079] Mucuna pruriens

[0080] Source: Sami Labs Limited, 19/1, 1.sup.st Main Rd, 2.sup.nd Phase, Nalagadderanahalli, Peenya, Bengaluru, Karnataka 560058, India. Geographical Origin: Native to Africa and tropical Asia and the Caribbean. In India, it is found in the Himalayas and Western Ghats.

[0081] Cynara cardunculus

[0082] Source: S V Agrofood, India 503/C, Panavally, P. O., Cherthala, Alappuzha, Kerala-688 526, India.

[0083] Geographical Origin: Native to western and central Mediterranean region.

[0084] Trigonella foenum graecum

[0085] Source: Sami Labs Limited, 9/1, 1.sup.st Main Rd, 2.sup.nd Phase, Nalagadderanahalii, Peenya, Bengaluru, Karnataka 560058, India.

[0086] Geographical Origin: Native to Western Mediterranean and spread throughout the Mediterranean region.

[0087] Withania somnifera

[0088] Source: Sami Labs Limited, 19/1, 1.sup.st Main Rd, 2.sup.nd Phase, Nalagadderanahalli, Peenya, Bengalum, Kamataka-560058, India.

[0089] Geographical Origin: Native to drier parts of India. Also found in Nepal, China and Yemen.

[0090] L-arginine L-arginine is of synthetic origin and is procured from K P Manish Global Ingredients Pvt. Ltd. 41, Raghunayakulu Street, Park Town, Chennai-600003, Tamil Nadu India.

[0091] The present invention provides a synergistic composition comprising herbal extracts of Mucuna pruriens, Cynara cardunculus, Trigonella foenum graecum, Withania somnifera and L-arginine along with pharmaceutically acceptable excipients, wherein said composition is having libido enhancing, testosterone increasing, erection enhancing, anxiety reducing and ejaculation delaying properties at the same time.

[0092] In the present invention, seeds of Mucuna pruriens, leaves of Cynara cardunculus, seeds of Trigonella foenum graecum and whole plant of Withania somnifera are used for preparing the respective extracts. The herbal extracts are prepared by using solvents selected from ethanol, methanol and water.

[0093] L-arginine used in the composition of present invention is an amino acid that helps to make proteins. L-arginine is important for the production of nitric oxide (NO) in the body which is required for proper erectile of penis. It exerts its activity through vasodilation, which increases the blood flow into the penile arteries leading to the penile erection. Healthy blood flow to the arteries of the penis is essential for normal erectile function.

[0094] Accordingly, in one embodiment, the present invention discloses a synergistic composition comprising herbal extracts of; [0095] a) Mucuna pruriens in an amount of 40 to 80 mg; [0096] b) Cynara cardunculus in an amount of 90 to 150 mg; [0097] c) Trigonella foenum graecum in an amount of 90 to 150 mg; [0098] d) Withania somnifera in an amount of 90 to 150 mg; [0099] e) L-arginine in an amount of 40 to 80 mg of the total weight of the composition and pharmaceutically acceptable excipients.

[0100] In another embodiment, the present invention discloses a synergistic composition comprising herbal extracts of; [0101] a) Mucuna pruriens in an amount of 50 mg; [0102] b) Cynara cardunculus in an amount of 100 mg; [0103] c) Trigonella foenum graecum in an amount of 100 mg; [0104] d) Withania somnifera in an amount of 100 mg; [0105] e) L-arginine in an amount of 50 mg of the total weight of the composition and pharmaceutically acceptable excipients.

[0106] In another embodiment, the present invention discloses a synergistic composition comprising herbal extracts of; [0107] a) Mucuna pruriens in an amount of 72.22 mg; [0108] b) Cynara cardunculus in an amount of 144.44 mg; [0109] c) Trigonella foenum graecum in an amount of 144.44 mg; [0110] d) Withania somnifera in an amount of 144.44 mg; [0111] e) L-arginine in an amount of 72.22 mg of the total weight of the composition and pharmaceutically acceptable excipients.

[0112] Various embodiments disclosed herein relate to an herbal composition comprising: [0113] a first extract selected from the group consisting of an extract of Mucuna pruriens, an extract of Rhodiola Rosea, an extract of horny goat weed, an extract of Asparagus racemosus, an extract of Hypericum perforatum, an extract of Butea Superba, an extract of Griffonia simplicifolia, an extract of Muira Puma, an extract of Damiana, and a mixture thereof; [0114] an extract of Cynara cardunculus, [0115] an extract of Trigonella foenum graecum, [0116] an extract of Withania somnifera, [0117] L-arginine, and [0118] a pharmaceutically acceptable excipient.

[0119] In various embodiments, the extract of Cynara cardunculus and at least one of the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in a second ratio of 1:1 by weight; [0120] the extract of Trigonella foenum graecum and the extract of Withania somnifera are present in the herbal composition in the second ratio of 1:1 by weight; and/or [0121] the first extract and at least one of the extract of Cynara cardunculus, the extract of Trigonella foenum graecum, and the extract of Withania somnifera are present in the herbal composition in a first ratio of 1:2 by weight.

[0122] Accordingly, in one embodiment, the present invention discloses a synergistic composition comprising herbal extracts of; [0123] a) a first extract which may be an extract of Mucuna pruriens, an extract of Rhodiola Rosea, an extract of horny goat weed, an extract of A an extract of Hypericum peoratum, an extract of Butea Superba, an extract of Griffonia simplicifolia, an extract of Muira Puma, an extract of Damiana, or a mixture thereof, the first extract being present in an amount of 40 to 80 mg; [0124] b) Cynara cardunculus in an amount of 90 to 150 mg; [0125] c) Trigonella foenum graecum in an amount of 90 to 150 mg; [0126] d) Withania somnifera in an amount of 90 to 150 mg; [0127] e) L-arginine in an amount of 40 to 80 mg of the total weight of the composition and pharmaceutically acceptable excipients.

[0128] The pharmaceutically acceptable excipients are selected from binder, glidants, lubricants, diluents, disintegrants, emulsifying agents, anti-caking agents, anti-adherents and granulating agents and the like. Said excipients are present in an amount of 40-70 mg of the total weight of the composition.

[0129] The pharmaceutical acceptable excipients used in present invention are Microcrystalline Cellulose and Silicon dioxide in an amount of 40 to 70 mg and 4 to 8 mg, respectively of total weight of the composition.

[0130] In another embodiment, the present composition can be formulated into tablet, capsule, granules, pills and the like, preferably a capsule.

[0131] In yet another embodiment, the present invention discloses a process for preparation of present synergistic herbal composition comprising; [0132] a) Sieving and weighing required quantities of Mucuna pruriens extract, Cynara cardunculus extract, Trigonella foenum graecum extract, Withania somnifera extract and L-Arginine separately; [0133] b) blending all the raw material of step (a) for 5 minutes at 25 rpm; [0134] c) adding microcrystalline cellulose and silicon dioxide into step (b) followed by blending for 10 minutes at 25 rpm to obtained homogenized mixture; [0135] d) filling the homogenized mixture of step (c) into size “0” capsule using capsule filling machine to obtain final product.

[0136] In yet another embodiment, the synergistic composition of present invention enhances sustained libido and erection through boosting testosterone levels.

[0137] In yet another embodiment, the synergistic composition of present invention increases intra-vaginal ejaculation latency time (IELT) leading superior sexual experience and sexual stamina; and also providing long term benefits in people/animal with low sex drive, low libido and in premature ejaculation without any side effects.

[0138] In another embodiment, the present invention demonstrates the efficacy of present composition (Example 2, coded as OLNP-05) versus placebo for the treatment of subjects with premature ejaculation (PE). There was a significant increase in IELT (Intra-vaginal Ejaculatory Latency Time) score in the OLNP-05 group as compared to placebo (p<0.05) (FIG. 1 and Table 2). The PEP (Premature Ejaculation Profile) score was found to be significantly improved in the OLNP-05 group, as compared to placebo treatment group. The subjects in the OLNP-05 treatment group reported significantly (p<0.05) greater improvement in PEP subscale score includes PEP control, PEP satisfaction, PEP distress and PEP relationship problems (FIG. 2 and Table 2).

[0139] In another embodiment, the present invention discloses an improvement in CGI-I (Clinical Global Impression-Improvement scale) in different visits. From Table 3, it is observed that, a greater proportion of mean in the OLNP-05 treated group, were found to be ‘Much improved’ category in the CGI-I assessment.

[0140] In another embodiment, OLNP-05 was found to be very safe and well tolerated in the clinical study.

[0141] In another embodiment, the present invention discloses acute oral toxicity study of the present composition. It is observed from Table 4 that, no clinical signs of toxicity and mortalities were observed in any of the dosed animals. Further, Table 5 depicts that, all animals in the test revealed physiologically normal increase in body weights during the observation period and Table 6 depicts that, no gross pathologically changes were observed in any of the animals.

[0142] In another embodiment, the present invention discloses Testosterone Study of the present composition. The synergy of the present composition (Example 2, OLNP-05) is achieved by a significant increase in total testosterone level and in free testosterone level over an individual extract and the same was demonstrated in Table 7.

[0143] In another embodiment, the present invention demonstrates the efficacy study of present composition (Example 2, coded as OLNP-05) versus capsule composition of U.S. Pat. No. 9,486,482 (Example 3, Table 6). The study indicates that the percentage improvement in the ejaculation profile is better in OLNP-05 compare to capsule composition of U.S. Pat. No. 9,486,482 and the same was depict in Table 8.

[0144] In yet another embodiment, the present invention discloses method of treating sexual disorders selected from enhancing libido, increasing testosterone levels, enhancing erection, reducing anxiety and delaying ejaculation comprising administering a synergistic herbal composition comprising extracts of Mucuna pruriens, Cynara cardunculus, Trigonella foenum graecum, Withania somnifera and L-arginine along with pharmaceutically acceptable excipients, to a subject in need thereof.

[0145] In yet another embodiment, the present invention discloses a synergistic herbal composition comprising extracts of Mucuna pruriens, Cynara cardunculus, Trigonella foenum graecum, Withania somnifera and L-arginine along with pharmaceutically acceptable excipients, useful for the treatment of sexual disorders selected from enhancing libido, increasing testosterone levels, enhancing erection, reducing anxiety and delaying ejaculation.

EXAMPLES

[0146] Some typical examples illustrating the embodiments of the present invention are provided; however, these are exemplary only and should not be regarded as limiting the elements of the present invention.

Example 1

[0147]

TABLE-US-00001 Sr. No. Ingredients Weight (mg)/Capsule 1. Mucuna pruriens extract 40 to 80 mg 2. Cynara cardunculus extract 90 to 150 mg 3. Trigonella foenum graecum extract 90 to 150 mg 4. Withania somnifera extract 90 to 150 mg 5. L-Arginine 40 to 80 mg 6. Microcrystalline Cellulose 40 to 70 mg 7. Silicon dioxide 4 to 8 mg

Example 2

[0148]

TABLE-US-00002 Weight Weight (mg)/ (gm)/ Sr. Capsule 100 gm No. Ingredients (450 mg) powder 1. Mucuna pruriens extract 50.00 11.11 2. Cynara cardunculus extract 100.00 22.22 3. Trigonella foenum graecum extract 100.00 22.22 4. Withania somnifera extract 100.00 22.22 5. L-Arginine 50.00 11.11 6. Microcrystalline Cellulose 45.00 10.00 7. Silicon dioxide 5.00 1.11 Total 450.00 100.00

Example 3

[0149] Process for preparation of Composition of Example 2: [0150] a) Sieving and weighing 50 mg of Mucuna pruriens extract, 100 mg of Cynara cardunculus extract, 100 mg of Trigonellafoenum graecum extract, 100 mg of Withania somnifera extract and 50 mg of L-Arginine separately; [0151] b) blending all the raw material of step (a) for 5 minutes at 25 rpm; [0152] c) adding 45 mg of microcrystalline cellulose and 5 mg of silicon dioxide into step (b) followed by blending for 10 minutes at 25 rpm to obtained homogenized mixture; [0153] d) filling the homogenized mixture of step (c) into size 0 transparent capsule using capsule filling machine to obtain final product.

Example 4:

[0154]

TABLE-US-00003 Weight Weight Sr. (mg)/ (gm)/ No. Ingredients Capsule 100 gm 1. Mucuna pruriens extract 72.22 11.11 2. Cynara cardunculus extract 144.44 22.22 3. Trigonella foenum graecum extract 144.44 22.22 4. Withania somnifera extract 144.44 22.22 5. L-Arginine 72.22 11.11 6. Micro Crystalline Cellulose 65.00 10.00 7. Silicon dioxide 7.22 1.11 Total 650.00 100.00

Example 5:

[0155] Process for preparation of Composition of Example 4: [0156] a) Sieving and weighing 72.22 mg of Mucuna pruriens extract, 144.44 mg of Cynara cardunculus extract, 144.44 mg of Trigonella foenum graecum extract, 144.44 mg of Withania somnifera extract and 72.22 mg of L-Arginine separately; [0157] b) blending all the raw material of step (a) for 5 minutes at 25 rpm; [0158] c) adding 65 mg of microcrystalline cellulose and 7.22 mg of silicon dioxide into step (b) followed by blending for 10 minutes at 25 rpm to obtained homogenized mixture; [0159] d) filling the homogenized mixture of step (c) into size 0 transparent capsule using capsule filling machine to obtain final product.

Example 6

Analytical Test Results

[0160] Example 2, Coded as OLNP-05 was tested for Total Saponins and total flavonoids by Gravimetric method and UV spec method respectively. The sample (Example 2) was also tested for heavy metals and microbiological parameters viz; total plate count, yeast and mold count, E. coli and salmonella content. The results are given in below Table 1.

TABLE-US-00004 TABLE 1 Analytical Test Result of OLNP-05 Sr. No. Test Parameters Test Result Test Method 1. Total Saponins 32.59% Gravimetric 2. Total Flavonoids  2.39% UV Spec (UV-Vis) 3. Lead 0.070 ppm AOAC 2015.01 by ICP-MS 4. Arsenic <0.05 ppm AOAC 2015.01 by ICP-MS 5. Mercury <0.01 ppm AOAC 2015.01 by ICP-MS 6. Total Plate Count 95 cfu/g ISO 4833-1: 2013 7. Total Yeast and <10 cfu/g ISO 21527-2: 2008 Mold Count 8. E. coli Absent/1 g IS 5887(Part 1): 1976 9. Salmonella Absent/25 g ISO 6579-1: 2017

Example 7

Experimental Details

[0161] A randomized, double-blind, placebo-control experimentation was designed to assess the efficacy and safety of the present composition (Example 2, coded as OLNP-05) versus placebo for the treatment of subjects with premature ejaculation (PE).

[0162] Methods:

[0163] The experiment was prospectively registered at the Clinical Trials Registry India (Registration No: CTRI/2017/08/009226, Feb. 8, 2017) and received approval from the Institutional Ethics Committee, Maharaja Agrasen Hospital, New Delhi, India prior to commencement of the study.

[0164] Total 60 males with PE were enrolled and randomly assigned to receive either OLNP-05 or placebo group. The subjects included in the experiment were provided with study medication for a period of 8 weeks, which includes study visits on day 1, day 28 and day 56. Subjects were advised to take one capsule of Example 2 (450 mg) twice daily. Mean change from baseline in Intra-vaginal Ejaculatory Latency Time (IELT), improvement in Premature Ejaculation Profile (PEP) and Clinical Global Impression-Improvement scale (CGI-I) were used to assess the efficacy of treatment. P value <0.05 was considered significant.

[0165] Results:

[0166] At the end of the treatment, the improvement in IELT score in the OLNP-05 group was significantly higher than the placebo (p<0.05). IELT score was increased from 1.25 min to 6.34 min at final visit in the OLNP-05 group and in placebo group the improvement was from 1.34 min to 1.81 min at the final visit (FIG. 1). The PEP control score was found to be significantly improved from 2.00±0.37 to 4.13±0.57 at final visit in the OLNP-05 group, whereas in the placebo treatment group the improvement was from 2.03±0.18 to 2.30±0.46. Subjects in the OLNP-05 treatment group reported significantly (p<0.05) greater improvement in PEP subscale score includes PEP control, PEP satisfaction, PEP distress and PEP relationship problems (FIG. 2). The mean change from baseline in efficacy criteria is given in below Table 2.

TABLE-US-00005 TABLE 2 Mean change from baseline in efficacy criteria OLNP-05 Capsule Placebo Capsule N = 30 N = 30 Mean Change from Mean Change from Visit (SD) baseline (SD) baseline P value Mean change in IELT (Min) Baseline  1.25 (0.15)  1.34 (0.25) Visit 2  4.11 (0.60) 2.86 (0.59)*{circumflex over ( )}  1.59 (0.97) 0.25 (0.93) <0.0001 Visit 3  6.34 (0.87) 5.09 (0.83)*{circumflex over ( )}  1.81 (1.43) 0.47 (1.35) <0.0001 Mean change in PEP Control Baseline  2.00 (0.37)  2.03 (0.18) Visit 2  3.03 (0.18) 1.03 (0.41)*{circumflex over ( )}  2.03 (0.18) 0.00 (0.26) <0.0001 Visit 3  4.13 (0.57) 2.13 (0.63)*{circumflex over ( )}  2.30 (0.46) 0.27 (0.44) * <0.0001 Mean change from baseline in PEP Satisfaction Score Baseline  2.40 (0.50)  2.20 (0.41) Visit 2  3.77 (0.43) 1.37 (0.67)*{circumflex over ( )}  2.37 (0.49) 0.16 (0.50) <0.0001 Visit 3  4.13 (0.57) 1.73 (0.78)*{circumflex over ( )}  2.47 (0.57) 0.27 (0.58)* <0.0001 Mean change in PEP Distress Score Baseline  3.63 (0.49)  3.73 (0.45) Visit 2  4.00 (0.26) 0.37 (0.49)*{circumflex over ( )}  3.73 (0.52) 0.00 (0.59)   0.0151 Visit 3  4.57 (0.57) 0.93 (0.64)*{circumflex over ( )}  3.83 (0.64) 0.10 (0.71) <0.0001 Mean change in PEP Relationship problem Score Baseline  3.60 (0.50)  3.83 (0.38) Visit 2  4.07 (0.25) 0.47 (0.57)*  3.90 (0.40) 0.07 (0.25)   0.0600 Visit 3  4.17 (0.38) 0.57 (0.63)*  4.00 (0.45) 0.17 (0.38)*   0.1286 Mean change from baseline in PEP Index Score Baseline 11.63 (0.72) 11.80 (0.61) Visit 2 14.87 (0.62) 3.23 (0.97)*{circumflex over ( )} 12.03 (0.76) 0.23 (0.73)   0.0001 Visit 3 17.00 (1.46) 5.37 (1.61)*{circumflex over ( )} 12.60 (1.35) 0.80 (1.30)*   0.0001 *Statistically significant (p < 0.05) within group; {circumflex over ( )}statistically significant (2 < 0.05) between group. Within group analysis by Pair t-test and between group analysis by unpaired t-test.

[0167] Improvement in CGI-I in different visits is given in Table 3. A greater proportion of mean in the OLNP-05 treated group, i.e. 19 (63.33%) were found to be ‘Much improved’ category in the CGI-I assessment.

TABLE-US-00006 TABLE 3 Improvement in Clinical Global Impression-Improvement scale in different visits Improvement in CGI-I in different visits OLNP-05 (N, %) Placebo (N, %) Visit 2 Visit 3 Visit 2 Visit 3 Not assessed = 0 — — — — Very much improved = 1 —  6 (20.00) — — Much improved = 2 2 (6.67) 19 (63.33) — — Minimally improved = 3 28 (93.33)  5 (16.67)  5 (15.67) 11 (36.67) No change = 4 — — 25 (83.33) 17 (56.67) Minimally worse = 5 — — — 2 (6.67) Much Worse = 6 — — — — Very much worse = 7 — — — —

[0168] There were no adverse events showing the product OLNP-05 is safe and well tolerated.

[0169] Conclusions:

[0170] The present experiments, demonstrate that the OLNP-05 is more effective compared with placebo in prolonging of IELT, improving in individual parameters of PE score and improvement in Clinical Global Impression. OLNP-05 was found to be safe and well tolerated during the study period.

Example 8

Acute Oral Toxicity Study

[0171] The test item OLNP-05 from Example 2 was evaluated for Acute Oral Toxicity in Sprague Dawley rats as per OECD Guidelines for Testing of Chemicals (NO. 425, Section 4: Health Effects) on conduct of “Acute Oral Toxicity-Up-and-Down-Procedure (UDP)” adopted on 3.sup.rd Oct. 2008. OLNP-05 was found to have LD50 greater than 5000 mg/kg body weight as per OECD Guideline No. 425-Acute Oral Toxicity, which indicates the higher safety profile of the composition.

[0172] Methods:

[0173] The limit test of 5000 mg/kg body weight was performed with three animals (Rats). All the animals were observed for clinical signs of toxicity at 30 to 40 min, 1 hr (±10mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) post dosing on day 1 and thereafter once daily for clinical signs of toxicity and twice for mortality during the 14 days observation period.

[0174] Results:

[0175] No clinical signs of toxicity and mortalities were observed at dose of 5000 mg/kg body weight in any of the dosed animals (Tables 4A and 4B). No changes were observed in body weight and percent change in any body weight with respect to Day 1 in all the animals. All the animals in the test revealed physiologically normal increase in body weights during the observation period (Table 5). No gross pathologically changes were observed in any of the animals (Table 6).

TABLE-US-00007 TABLE 4A Individual animal clinical signs of toxicity and mortality on Day 1 Dose (mg/kg Clinical Signs of Toxicity on Day 1 body Animal 30-40 1 hr 2 hrs 3 hrs 4 hrs Test weight) No. Sex min (±10 min) (±10 min) (±10 min) (±10 min) Limit 5000 Rd5681 F N N N N N Test Rd5682 F N N N N N Rd5683 F N N N N N F: Female; N: Normal

TABLE-US-00008 TABLE 4B Individual animal clinical signs of toxicity and mortality record on Days 2 to 15 Dose (mg/kg Clinical Signs of Toxicity body Animal Day Test weight) No. Sex 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Limit 5000 Rd5681 F N N N N N N N N N N N N N N Test Rd5682 F N N N N N N N N N N N N N N Rd5683 F N N N N N N N N N N N N N N F: Female; N: Normal

TABLE-US-00009 TABLE 5 Individual animal body weight (g) and percent change in body weight with respect to Day 1 Dose Percent Change in (mg/kg Body Weight with body Animal Body Weight (g) on Day Respect to Day Test weight) No. Sex 1 8 15 1 to 8 1 to 15 Limit 5000 Rd5681 F 167.50 190.14 212.64 13.52 26.95 Test Rd5682 F 189.62 214.49 238.27 13.12 25.66 Rd5683 F 184.96 206.11 228.90 11.43 23.76 F: Female

TABLE-US-00010 TABLE 6 Individual animal gross pathology findings Dose (mg/kg body Animal Gross Pathology Findings Test weight) No. Sex Fate External Internal Limit 5000 Rd5681 F TS NAD NAD Test Rd5682 F TS NAD NAD Rd5683 F TS NAD NAD F: Female; NAD: No Abnormality Detected; TS: Terminal sacrifice

[0176] Conclusion: Under the experiment conditions employed and based on the observed results of experiment, it is concluded that the estimated LD50 of test item OLNP-05 is greater than 5000 mg/kg body weight as per OECD Guideline [No. 425-Acute Oral Toxicity-Up-and-Down Procedure (AOT425 statpgm)], when administered as a single dose by oral gavage to Sprague Dawley Rats. Hence, the test item, OLNP-05 does not fall under classification criteria according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Example 9

Total Testosterone Study

[0177] An experiment was conducted enrolling 3 male cyclists who were dosed with 450 mg of OLNP-05 capsules twice daily for a period of 4 weeks. At the end of the study period total serum testosterone level was evaluated. The results are shown in below Table 7. In Table 7, the free testosterone test measures the amount of unattached, or “free,” testosterone in blood. The total testosterone test measures testosterone that is bound to proteins in the blood (e.g., albumin and sex-hormone binding globulin [SHBG]) as well as testosterone that is not bound (free testosterone). Typically, a test for total testosterone is used for diagnosis.

TABLE-US-00011 TABLE 7 Free testosterone Total testosterone Study Pre-treatment Post treatment % Pre-treatment Post treatment % Sample duration Dose level levels Increase level levels Increase Fenugreek 12 weeks 600mg/day.sup.1 8.17 pg/ml 11.97 pg/ml  46.51% 405.19 ng/dl 436.34 ng/dl    7% extract 8 weeks 300 mg of 17.76 ng/dl 35.29 ng/dl  98.70% — — twice daily.sup.2 Mucuna 3 months 5000 mg/day — — — 4.49 ng/ml 5.72 ng/ml  27.39% extract (Subject normozoo- spermic).sup.3 Cynara — — — — — — — — extract Aswa-gandha 8 weeks 300 mg of — — — 630.45 ng/dl 726.64 ng/dl  15.25% twice daily.sup.4 16 weeks delivering 21 — — — 346.56 pmol/L 378.38 pmol/L  9.18% mg of withanolide glycosides a day.sup.5 OLNP-05 4 weeks 450 mg of 3.285 pg/ml 9.385 pg/ml 185.69% 168.5 ng/dl 413.0 ng/dl 145.10% twice daily 1. Maheshwari et al, Int. J. Med. Sci. 2017, Vol 14 58-66. 2. Wankhede et al, Journal of Sport and Health Science 5 (2016) 176-182. 3. Shukla et al., Fertility and Sterility (2009), Vol 92, No. 6, 1934-1940. 4. Wankhede et al., Journal of the International Society of Sports Nutrition (2015) 12; 1-11. 5. Lopresti et al., American Journal of Men's Health (2019) 1-15. pg/ml-picogram/millilitre ng/dl-nanogram/decilitre

[0178] Conclusion: A significant increase in total testosterone level (145.10%) and in free testosterone level (185.69%) was observed from OLNP-05 in the above Table 7.

Example 10

Ejaculation Profile Study

[0179] A triple blind, randomized, double dummy, prospective placebo controlled, dose determination study was conducted by the developer (U.S. Pat. No. 9,486,482B2). The capsule composition containing Withania somnfera extract 120 mg/capsule and Mucuna prurines extract 50 mg/capsule along with other herbal extracts was studied in 147 subjects [Example 3, Table 6 of U.S. Pat. No. 9,486,482] with male sexual dysfunction (Erectile

[0180] Dysfunction and/or low libido and sexual dissatisfaction and/or premature ejaculation). Index for Premature Ejaculation, IPE, International Index of Erectile Function IIEF-A, IIEF-B, IIEF (A+B) was evaluated and the data for the IPE is given in the Table 8 below.

TABLE-US-00012 TABLE 8 Intra- Pre- Index % vaginal mature for pre- imrove- Free testosterone Total testosterone Vaginal ejacula- mature ment in Pre- Post % Pre- Post % Latency tion ejacula- ejacula- Study treatment treatment treatment treatment Time profile tion tion Sample duration Dose level levels Increase level levels Increase (IELT) (PEP) (IPE) profile OLNP-05 4 weeks 450 mg 3.285 9.385 185.69%  168.5  413.0 145.10% 1.25 2.00 ± — 106.50% capsules pg/ml pg/ml ng/dl ng/dl min to 0.37 to twice 6.34 4.13 ± daily min 0.57 Example 3, 2 month 520 mg — — — 513.44 430.57  −0.00% — — 26.88 ±  42.30% Table 6 of capsules  5.93 to US94564S2 twice 39.23 ± daily  5.77

[0181] Conclusion: The study indicates that the percentage improvement in the ejaculation profile is better in OLNP-05 (106.50%) compare to the capsule composition of U.S. Pat. No. 9,486,482 (42.30%).

REFERENCE

[0182] 1. Kavitha and Thangamani. 2014. Amazing bean “Mucuna pruriens”: A comprehensive review. Journal of Medicinal Plants Research. Vol. 8. p. 138-143. [0183] 2. Chauhan Sharma, Dixit and Thakur. 2014. A Review on Plants Used for

[0184] Improvement of Sexual Performance and Virility. BioMed Research International. Vol. 2014. [0185] 3. Bichitra N Nayak and Harpal S Buttar. Herbal therapy for men with erectile dysfunction. Curr Res Cardiol 2015; 2(1):30-34. [0186] 4. S. E. Althof, C. G. McMahon, M. D. Waldinger, et al. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE) The Journal of Sexual Medicine, 11 (2014), pp. 1392-1422. [0187] 5. E. C. Serefoglu, C. G. McMahon, M. D. Waldinger, et al. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the Second International Society for Sexual Medicine Ad Hoc Committee for the definition of premature ejaculation The Journal of Sexual Medicine, 11 (2014), pp. 1423-1441.