Application of traditional Chinese medicine composition in preparation of medicine for treating male sexual function and resisting fatigue

Abstract

The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for treating male sexual function and resisting fatigue, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is mainly prepared from astragalus membranaceus, scutellaria baicalensis, rhizoma alismatis, salvia miltiorrhiza and ginseng. Experiments prove that the traditional Chinese medicine composition has the effects of obviously improving the male sexual function and resisting fatigue. The traditional Chinese medicine composition can effectively solve the problems that an existing composition is not ideal in treatment effect and excessive in component, and meanwhile the oral traditional Chinese medicine composition preparation is high in safety and small in toxic and side effect.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to the application of a traditional Chinese medicine composition in preparing a medicine for treating male sexual dysfunction and anti-fatigue. Background Art

[0002] With the continuous improvement of the quality of life, more and more men begin to pay attention to their own health conditions, and the harmony of marital relationships has also received increasing attention. Among them, male sexual dysfunction has become a key factor affecting the harmony of marital relationships. The main clinical manifestations of this disorder include symptoms such as impotence, premature ejaculation, and spermatorrhea, which make it impossible for patients to have sex smoothly, greatly interfere with their daily lives, and in severe cases, may also cause infertility problems. At present, the main means of treating male sexual dysfunction is Western medicine, which has large side effects such as headache, nasal congestion, muscle pain, blurred vision, facial flushing, etc., and cannot be taken for a long time. Even taking hormone drugs can aggravate sexual dysfunction or even completely lose it. Traditional Chinese medicine treatment has the advantages of few adverse reactions, suitable for long-term use, safe and reliable, and low price. It is more and more widely used in the clinical treatment of this disease with traditional Chinese medicine.

[0003] Fatigue is a complex physiological and psychological phenomenon of mental or physical tiredness and decreased endurance. It can be divided into central fatigue and peripheral fatigue. Its occurrence is related to many factors, including the accumulation of metabolic substances in tissues, insufficient energy supply, oxidative stress, muscle damage, etc. Long-term fatigue may cause the occurrence of diseases such as cancer, depression, and multiple sclerosis. It is also a warning signal of the body's "fragile" response. In addition, when muscle fatigue occurs, the input of sensory information and the output of motor information of the body change, muscle strength and posture control ability decrease, and it may also have a certain impact on sexual activity ability. It may take a long time to improve or relieve fatigue symptoms, but long-term use of chemical drugs may cause some adverse reactions or toxic effects.

[0004] Whether it is sexual dysfunction or chronic fatigue, both seriously affect people's quality of life and health. It is of positive significance to develop traditional Chinese medicines or health products with clear active functions.

[0005] Chinese patent CN103566087A discloses a pharmaceutical composition for treating cognitive dysfunction, which is composed of Astragalus, Scutellaria, Rhizoma Alismatis, Salvia miltiorrhiza and Ginseng, and can improve cognitive dysfunction, treat Alzheimer's disease, improve glucose metabolism level, and increase the content of monoamine neurotransmitters in the brain. The pharmaceutical composition can inhibit the expression of APP, Aβ-40, and Aβ-42 in brain tissue, can significantly improve the learning and memory ability of scopolamine-induced dementia mice, reduce brain tissue ACHE activity, and has a good anti-dementia effect. In the treatment of Alzheimer's disease, the glucose metabolism level of dementia model mice can be significantly improved, and the content of norepinephrine, dopamine and serotonin in the cerebral cortex of rapid brain aging mice can be increased.

[0006] At present, there has been no research or report on the use of a pharmaceutical composition for treating cognitive dysfunction disclosed in Chinese patent CN103566087A in treating male sexual function and anti-fatigue. Summary of the invention

[0007] The present invention is a new use unexpectedly discovered and developed on the basis of a pharmaceutical composition for treating cognitive dysfunction disclosed in Chinese patent CN103566087A, and specifically provides an application of a traditional Chinese medicine composition in the preparation of drugs for treating male sexual dysfunction and anti-fatigue.

[0008] Preferably, the traditional Chinese medicine composition mainly consists of Astragalus, Scutellaria, Alismatis, Salvia miltiorrhiza and Ginseng.

[0009] Preferably, the Chinese medicine composition mainly comprises the following components by weight: 15 parts of Astragalus, 9 parts of Scutellaria, 9 parts of Alisma, 9 parts of Salvia miltiorrhiza, and 6 parts of Ginseng.

[0010] Preferably, the pharmaceutical preparation consists of the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0011] Preferably, the Chinese medicine composition pharmaceutical preparation is a capsule, tablet, granule, mixture, pill, pellet, effervescent tablet, syrup, oral liquid, powder or granule, etc., a lyophilized powder injection and injection solution used for parenteral administration, etc.

[0012] Preferably, the Chinese medicine composition preparation is a granule.

[0013] Preferably, the granules are made of the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients in a weight ratio of 1:1.5-8.5; preferably, the traditional Chinese medicine composition and pharmaceutically acceptable excipients are made of a weight ratio of 1:2.0-5.5.

[0014] Preferably, the pharmaceutically acceptable excipients of the granules include fillers and binders, the filler is one or more of mannitol, lactose, sorbitol, sucrose, and cyclodextrin; the binder is one or more of 3% PVP in 75% ethanol solution, 3% hydroxypropyl methylcellulose in 50% ethanol solution, 10% povidone K30 aqueous solution, and 30% starch slurry.

[0015] Preferably, the filler is a mixture of cyclodextrin and sorbitol, and the ratio of cyclodextrin to sorbitol is 1:0.5-1.4 calculated by weight ratio; preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0016] Preferably, the method for preparing the Chinese medicine composition pharmaceutical preparation comprises the following steps:

[0017] (1) Grind ginseng and sieve it into fine powder for later use;

[0018] (2) Weighing astragalus, scutellaria, and orientalis according to the ratio, soaking in water, boiling, filtering, and concentrating to obtain a concentrated solution;

[0019] (3) weighing Salvia miltiorrhiza according to the ratio, removing impurities, washing, drying, grinding and sieving to obtain fine powder;

[0020] (4) combining the fine powder obtained in the above step (1) and the concentrated solution obtained in step (2), mixing them evenly, concentrating them into a thick paste, drying them under reduced pressure, crushing them, sieving them, and mixing them with the fine powder obtained in step (3) to obtain a Chinese medicine composition;

[0021] (5) The Chinese medicine composition of step (4) is mixed evenly with the filler, and then mixed with a binder to form granules, thereby obtaining a Chinese medicine composition pharmaceutical preparation.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention provides a new use of a Chinese medicine composition in preparing a medicine for treating male sexual dysfunction and anti-fatigue, and animal experiments and clinical trials prove that the Chinese medicine composition has a significant effect of improving male sexual function and an anti-fatigue effect.

[0024] The Chinese medicine combination formula is simple, the number of medicinal flavors and the number of medicinal materials used are small, which saves resources while also reducing medication costs, has high safety, and has few toxic and side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Effects of Chinese herbal medicine combination on the number of captures of ICR male mice (n=10)

[0026] Figure 2 Effects of Chinese herbal medicine combination on capture latency of ICR male mice (n=10)

[0027] Figure 3 Effects of Chinese herbal medicine combination on ejaculation latency of ICR male mice (n=10)

[0028] Figure 4 Effects of Chinese herbal medicine combination on the number of ejaculations in ICR male mice (n=10)

[0029] Figure 5 Effects of Chinese herbal medicine combination on serum testosterone and NO levels in ICR male mice (n=10)

[0030] Figure 6 Effects of Chinese herbal medicine combination on gonadal organ index of ICR male mice (n=10)

[0031] Figure 7 Effects of Chinese herbal medicine combination on cGMP content in cavernous body of ICR male mice (n=10)

[0032] Figure 8 Effects of Chinese herbal medicine combination on PDE5 content in cavernous body of ICR male mice (n=10)

[0033] Fig. 9 Effects of Chinese herbal medicine combination on anti-fatigue index-LDH in ICR male mice (n=10)

[0034] Fig.10 Effects of Chinese herbal medicine combination on anti-fatigue index-LA in ICR male mice (n=10)

[0035] Fig.11 Effects of Chinese herbal medicine combination on anti-fatigue index-BUN of ICR male mice (n=10)

[0036] Fig.12 Effects of Chinese herbal medicine combination on liver glycogen, an anti-fatigue index of ICR male mice (n=10)

[0037] Fig.13 Effects of Chinese herbal medicine combination on anti-fatigue index-muscle glycogen in ICR male mice (n=10)

[0038] Fig.14 Effects of Chinese herbal medicine combination on MDA, an anti-fatigue index of ICR male mice (n=10) DETAILED DESCRIPTION

[0039] The following are specific embodiments of the present invention, which further describe the technical solutions of the present invention in detail, but it should not be understood that the present invention is limited to the following implementation cases within the scope of the above-mentioned subject. Without departing from the above-mentioned technical premise of the present invention, the corresponding replacement or modification made according to the common technical knowledge and customary means in the field are all included in the present invention.

[0040] 1. Preparation of Chinese medicine composition granules

[0041] Example 1

[0042] The granules described in this embodiment have the following raw material prescription amounts:

[0043] Weigh 15g of Astragalus, 9g of Scutellaria, 9g of Alisma, 9g of Salvia, and 6g of Ginseng;

[0044] The preparation method of the granules is:

[0045] (1) Grind the prescribed amount of ginseng through an 80-mesh sieve to obtain fine powder for later use;

[0046] (2) Weigh astragalus, scutellaria, and orientalis according to the ratio, add 12 times the amount of water, soak for 1.5 hours, boil over high heat for 15 minutes, filter to obtain the filtrate, and set aside the residue. Add 6 times the amount of water to the residue, boil over high heat, then boil over low heat for 1.5 hours, filter to obtain the filtrate, combine the two filtrates, and concentrate the filtrate to a relative density of 1.10 at 70°C to obtain a concentrated solution;

[0047] (3) weighing Salvia miltiorrhiza according to the ratio, removing impurities, washing, drying, grinding, and sieving through a 60-80 mesh sieve to obtain fine powder;

[0048] (4) The concentrated solution obtained in the above step (2) and the fine powder obtained in the step (1) are combined, mixed evenly, concentrated into a thick paste, the pH value is adjusted to 5.5, dried under reduced pressure, crushed and sieved through a 70-mesh sieve, and mixed with the fine powder in step (3) to obtain a Chinese medicine composition.

[0049] (5) Weigh the Chinese medicine composition obtained in step (4), add 1.5 times the weight of sorbitol and hydroxypropyl-β-cyclodextrin and mix evenly (the weight ratio of sorbitol to hydroxypropyl-β-cyclodextrin is 1:1), and then mix with an appropriate amount of 50% ethanol solution of 3% hydroxypropyl methylcellulose with a pH value of 6.0 to obtain granules.

[0050] Example 2

[0051] Step (5) in the granule preparation method described in this example is: weigh the Chinese medicine composition obtained in step (4), add 1.5 times the weight of hydroxypropyl-β-cyclodextrin and sorbitol and mix them evenly (the weight ratio of hydroxypropyl-β-cyclodextrin and sorbitol is 1:0.8), and then mix and granulate with an appropriate amount of 50% ethanol solution of 3% hydroxypropyl methylcellulose with a pH value of 6.0 to obtain granules.

[0052] Example 3

[0053] Step (5) in the granule preparation method described in this example is: weigh the Chinese medicine composition obtained in step (4), add 1.5 times the weight of hydroxypropyl-p-cyclodextrin and sorbitol and mix them evenly (the weight ratio of hydroxypropyl-p-cyclodextrin and sorbitol is 1:1.2), and then mix and granulate with an appropriate amount of 50% ethanol solution of 3% hydroxypropyl methylcellulose with a pH value of 6.0 to obtain granules.

[0054] Comparative Example 1

[0055] Step (5) in the granule preparation method described in this example is: weigh the Chinese medicine composition obtained in step (4), add 1.5 times the weight of hydroxypropyl-β-cyclodextrin and sorbitol and mix them evenly (the weight ratio of hydroxypropyl-β-cyclodextrin and sorbitol is 2.0:1), and then mix and granulate with an appropriate amount of 50% ethanol solution of 3% hydroxypropyl methylcellulose with a pH value of 6.0 to obtain granules.

[0056] Comparative Example 2

[0057] Step (5) in the method for preparing granules described in this example is: weigh the Chinese medicine composition obtained in step (4), add 1.0 times the weight of sorbitol and hydroxypropyl-β-cyclodextrin and mix them evenly (the weight ratio of sorbitol to hydroxypropyl-β-cyclodextrin is 0.8:1.0), and then mix and granulate with an appropriate amount of 50% ethanol solution of 3% hydroxypropyl methylcellulose with a pH value of 6.0 to obtain granules.

[0058] Verification example:

[0059] The physical and chemical indexes of Examples 1 to 3 of the present invention and Comparative Examples 1 to 2 were measured.

[0060] The granules prepared in Examples 1 to 3 of the present invention and Comparative Examples 1 to 2 were tested for moisture content, particle size, loss on drying and long-term storage. The test results are shown in Table 1.

[0061] Method for determining moisture content: The moisture content of the granules is calculated using the drying method and shall not exceed 8.0%.

[0062] Particle size detection method: The granules prepared in Examples 1 to 3 and Comparative Examples 1 to 2 were subjected to particle size determination according to the double screening method, Method 2, General Rules 0982, Part 4 of the 2020 edition of the Chinese Pharmacopoeia. The sum of the particles that cannot pass through the No. 1 sieve and the particles that can pass through the No. 5 sieve shall not exceed 15%.

[0063] Loss on drying: The granules prepared in Examples 1 to 3 and Comparative Examples 1 to 2 were measured according to the loss on drying method in Part 4 of the Chinese Pharmacopoeia 2020 edition, General Rules 0831, and dried at 105°C until the weight loss did not exceed 2.0%.

[0064] Long-term test: The granules prepared in Examples 1 to 3 and Comparative Examples 1 to 2 were placed at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10% for 12 months, and then the moisture content and the loss on drying were tested.

[0065] Table 1 Stability test results of each embodiment group

[0066]

[0067]

[0068] Note: One means that long-term testing was not carried out because the quality did not meet the requirements.

[0069] Table 1 shows that the granules of Examples 1 to 3 of the present invention meet the requirements in terms of water content, particle size and drying loss, and are qualified after long-term tests, especially the various indicators of Example 1 are better than those of other examples; the weight proportions of fillers in Comparative Examples 1 to 2 are not within the scope of the present invention, and the water content, particle size and drying loss are all unqualified, and the technical effect of the present invention cannot be achieved.

[0070] 2. Animal Experiments

[0071] 1 Materials

[0072] Animals: Healthy ICR mice.

[0073] Reagents: Nitric Oxide (NO) kit, Testosterone (T) enzyme-linked immunosorbent assay (ELISA) kit, Cyclic Guanosine Monophosphate (cGMP) kit, Phosphodiesterase 5 (PDE5) kit, Lactate (LA) kit, Lactate dehydrogenase (LDH) kit, Blood Urea Nitrogen (BUN) kit, Malondialdehyde (MDA), Liver Glycogen (LG) and Muscle Glycogen (MG) kits.

[0074] 2 Methods

[0075] 2.1 Feeding

[0076] Healthy ICR mice were adaptively fed for one week, and the health status of the animals was observed. There were 10 animals in each cage, and the animal cages were covered with sterilized cork shavings. The temperature of the animal laboratory was maintained at 23-25°C, the relative humidity was 50%-60%, the ventilation frequency was about 12 times / h, and the lighting was 12h light / 12h dark. The animal feed was stick-shaped, dried feed, and drinking water was free.

[0077] 2.2 Grouping and medication

[0078] 40 healthy adult male ICR mice, weighing 35-40g, were randomly divided into four groups: a low-dose group of Chinese medicine composition, a high-dose group of Chinese medicine composition, a positive control group of whey protein, and a blank control group, with 10 mice in each group. The mice in the low-dose and high-dose groups of Chinese medicine composition were gavaged at 0.24g / kg and 0.48g / kg, respectively, with purified water as the solvent. The positive control group was gavaged with whey protein at 0.50g / kg, with purified water as the solvent. The blank control group was gavaged with purified water. The mice were gavaged twice a day for 30 consecutive days.

[0079] Forty female mice were given normal chow and had free access to food and water.

[0080] 2.3 Male mouse mating experiment

[0081] The mating experiment was conducted 60 minutes after the last oral administration of male mice. Female mice were given estradiol benzoate 3 days before the mating experiment, at a subcutaneous injection of 10 μg per mouse, and progesterone was given 5 hours before the experiment, at a subcutaneous injection of 40 μg per mouse, to enter the estrus period. At 20:00-23:00 on the evening of the end of the oral administration of male mice, each group of male mice was placed in a cage of 30 cm × 15 cm × 15 cm in a quiet, dimly lit room for 15 minutes to adapt, and then the female mice were put in, and the mating behavior of the mice was observed within 30 minutes. The sexual behavior parameters of male mice in each group were counted, including the number of captures (the number of times the male mice captured the female mice); the capture latency (the time interval for the first capture behavior of the male mice); the ejaculation latency (the time interval from the placement of the female mice to the first ejaculation of the male mice); and the number of ejaculations (the total number of ejaculations of the male mice).

[0082] 2.4 Detection of NO and testosterone levels in male mouse serum

[0083] The animals were weighed the day before being killed, and fasted but not watered for 16 hours that night. The next day, blood was collected from the eyeball after ether anesthesia, centrifuged at 4°C and 3000 r / min for 15 minutes, and serum was separated to determine the NO and testosterone levels in the serum.

[0084] 2.5 Determination of sexual organ index, cGMP and PDE5 content

[0085] After blood collection, mice were killed by cervical dislocation, and the testicles, epididymis, preputial glands, seminal vesicles and prostate tissues of mice were removed and weighed, and the organ index was calculated (organ weight / mouse body weight × 100). The cavernous tissues on both sides of the mouse penis were peeled off in an ice bath, and the cGMP and PDE5 contents therein were detected.

[0086] 2.6 Anti-fatigue function evaluation

[0087] 40 male mice were randomly divided into 4 groups, and the grouping, dosage and administration method were the same as 2.2, and the administration was carried out for 30 days. After the last administration, all animals rested for 30 minutes and then swam in the swimming pool without load for 30 minutes. Blood samples were collected from the retro-ocular vein immediately after swimming for 30 minutes, and serum was obtained by centrifugation at 3000r / min for 10 minutes. LDH activity, LA and BUN content in mouse serum were determined.

[0088] The skeletal muscle of mice was stripped for the determination of muscle glycogen and MDA content, and the liver tissue of mice was stripped for the determination of liver glycogen content.

[0089] 2.7 Statistical methods

[0090] The results of the above indicators are expressed as mean ± standard deviation. GraphPad Prism 8 statistical software was used for statistical analysis by One-way ANOVA. P < 0.05 indicated that the difference was statistically significant, and P < 0.01 indicated that there was a significant statistical difference.

[0091] 3 Experimental results

[0092] 3.1 Effects of Chinese herbal medicine combination on mating behavior of ICR male mice

[0093] Table 2 Effects of Chinese herbal medicine composition on mating behavior of mice

[0094]

[0095]

[0096] Note: a means P<0.05 compared with the blank control group; b means P<0.01 compared with the blank control group; c means P<0.05 compared with the whey protein group; d means P<0.01 compared with the whey protein group.

[0097] Compared with the blank control group, the number of captures and ejaculations within 30 minutes in the whey protein group increased slightly but the difference was not statistically significant (P>0.05), increased in the low-dose Chinese medicine combination group (P<0.05), and significantly increased in the high-dose Chinese medicine combination group (P<0.01); compared with the blank control group, the capture latency and ejaculation latency within 30 minutes in the whey protein group and the low-dose Chinese medicine combination group were shortened (P<0.05), and significantly shortened in the high-dose Chinese medicine combination group (P<0.01).

[0098] Compared with the whey protein group, the number of captures and ejaculations within 30 minutes of mice in the low-dose Chinese medicine combination group increased slightly but the difference was not statistically significant (P>0.05), and increased significantly in the high-dose Chinese medicine group (P<0.01); the capture latency and ejaculation latency within 30 minutes of mice were shortened in the low-dose Chinese medicine combination group (P<0.05), and shortened significantly in the high-dose Chinese medicine group (P<0.01).

[0099] The experimental results show that the Chinese medicine combination of the present invention increases the number of captures and ejaculations of male mice and shortens the capture latency and ejaculation latency, indicating that the Chinese medicine combination of the present invention can improve the sexual function of mice.

[0100] 3.2 Effects of Chinese herbal medicine combination on serum testosterone and NO levels in ICR male mice

[0101] Table 3 Effect of Chinese medicine combination on serum testosterone and NO levels in mice

[0102] Group Blank control group Whey protein group Chinese medicine combination low dose group Chinese medicine combination high dose group Testosterone concentration (nmol / L) 53.16±21.40 54.30±21.11 <![CDATA[60.28±19.95 ac ]]> <![CDATA[67.28±12.11 bd ]]> NO concentration (nmol / L) 44.18±10.77 45.20±20.81 <![CDATA[51.07±14.12 ac ]]> <![CDATA[59.27±20.90 bd ]]>

[0103] Note: a means P<0.05 compared with the blank control group; b means P<0.01 compared with the blank control group; c means P<0.05 compared with the whey protein group; d means P<0.01 compared with the whey protein group.

[0104] Compared with the blank control group, the levels of testosterone and NO in the serum of the whey protein group were increased, but there was no statistical significance (P>0.05); the levels of testosterone and NO in the low-dose Chinese medicine combination group were increased (P<0.05); and the levels of testosterone and NO in the serum of mice in the high-dose Chinese medicine combination group were significantly increased (P<0.01).

[0105] Compared with the whey protein group, the levels of testosterone and NO in serum of the low-dose Chinese medicine combination group increased (P<0.05); the levels of testosterone and NO in serum of mice in the high-dose Chinese medicine combination group increased significantly (P<0.01).

[0106] NO is a non-cholinergic and non-adrenal neurotransmitter that can cause relaxation of the penile smooth muscle and allow blood to enter the corpus cavernosum. As the NO concentration increases significantly, the ability to stimulate penile erection increases. The experimental results show that the Chinese medicine combination group can increase the testosterone and NO levels of male mice, indicating that the Chinese medicine combination of the present invention can improve the ability of penile erection.

[0107] 3.3 Effects of Chinese herbal medicine combination on gonadal organ index of ICR male mice

[0108] Table 4 Effect of Chinese medicine composition on gonad organ index of mice

[0109] Group Blank control group Whey protein group Chinese medicine combination low dose group Chinese medicine combination high dose group Testicles (bilateral) 0.77±0.03 0.78±0.03 0.81±0.09 0.83±0.07 Epididymis (bilateral) 0.25±0.05 0.26±0.05 0.30±0.08 0.31±0.02 Preputial glands (bilateral) 0.29±0.07 0.30±0.02 0.32±0.03 0.32±0.08 Seminal vesicle + prostate 0.56±0.05 0.57±0.07 0.62±0.09 0.73±0.04ac

[0110] Note: a means P<0.05 compared with the blank control group; c means P<0.05 compared with the whey protein group.

[0111] Compared with the blank control group, there was no statistically significant difference in the gonad organ index of mice in the whey protein group (P>0.05); the gonad organ index of mice in the low-dose Chinese medicine combination group showed an upward trend but without statistical significance (P>0.05), and the gonad organ (seminal vesicle + prostate) index of mice in the high-dose Chinese medicine combination group increased (P<0.05).

[0112] Compared with the whey protein group, there was no statistically significant difference in the gonad organ index of mice in the low-dose Chinese medicine combination group (P>0.05), while the gonad organ index (seminal vesicle + prostate) of mice in the high-dose Chinese medicine combination group was increased (P<0.05).

[0113] The experimental results show that the Chinese medicine combination of the present invention can increase the gonad organ (seminal vesicle + prostate) index of male mice and can improve the sexual function of male mice.

[0114] 3.4 Effects of Chinese herbal medicine combination on cGMP and PDE5 levels in the cavernous body of ICR male mice

[0115] Table 5 Effect of Chinese medicine combination on cGMP and PDE5 content in mouse corpus cavernosum

[0116] Group Blank control group Whey protein group Chinese medicine combination low dose group Chinese medicine combination high dose group cGMP (nmol / L) 25.26±2.16 27.26±1.22 28.18±3.19 <![CDATA[33.22±2.11 bc ]]> PDE5(pg / L) 355.42±28.19 340.40±20.11 <![CDATA[304.14±31.24 ac ]]> <![CDATA[270.20±30.02 bd ]]>

[0117] Note: a means P<0.05 compared with the blank control group; b means P<0.01 compared with the blank control group; c means P<0.05 compared with the whey protein group; d means P<0.01 compared with the whey protein group.

[0118] Compared with the blank control group, there was no statistical difference in the cGMP and PDE5 contents in the cavernous body of mice in the whey protein group (P>0.05); the cGMP content in the low-dose Chinese medicine combination group increased slightly but had no statistical difference (P>0.05), and the PDE5 content decreased (P<0.05); the cGMP content in the high-dose Chinese medicine group increased significantly (P<0.01), and the PDE5 content decreased significantly (P<0.01).

[0119] Compared with the whey protein group, the cGMP content in the low-dose Chinese medicine combination group increased slightly but there was no statistical difference (P>0.05), and the PDE5 content decreased (P<0.05); the cGMP content in the high-dose Chinese medicine group increased (P<0.05), and the PDE5 content decreased significantly (P<0.01).

[0120] The decrease in PDE5 levels and the increase in cGMP levels allow the penis arterioles and cavernous smooth muscles to relax, allowing blood to be rapidly pumped into the cavernous sinus, causing erection. The experimental results show that the Chinese medicine combination of the present invention can increase the cGMP level and decrease the PDE5 level in male mice, thereby improving the erectile ability of male mice.

[0121] 3.5 Effects of Chinese medicine combination on anti-fatigue related indicators in mice

[0122] Table 6 Effects of Chinese medicine combination on anti-fatigue related indicators in mice

[0123] Group Blank control group Whey protein group Chinese medicine combination low dose group Chinese medicine combination high dose group LDH(U / L) 422.55±26.77 413.27±22.56 <![CDATA[400.77±23.39 ac ]]> <![CDATA[393.22±20.11 bd ]]> LA (nmol / L) 1.31±0.25 1.23±0.11 <![CDATA[1.10±0.13 ac ]]> <![CDATA[0.57±0.17 bd ]]> BUN (nmol / L) 4.75±1.11 4.55±1.54 <![CDATA[3.93±2.01 ac ]]> <![CDATA[3.22±0.90 bd ]]> Liver glycogen (mg / g) 4.71±0.22 5.03±0.35 <![CDATA[7.34±0.97 ac ]]> <![CDATA[9.08±0.88 bd ]]> Muscle glycogen (mg / g) 0.11±0.01 0.15±0.04 <![CDATA[0.18±0.02 ac ]]> <![CDATA[0.25±0.11 bd ]]> MDA (nmol / m1) 6.02±0.37 5.80±0.54 <![CDATA[4.75±0.22 ac ]]> <![CDATA[3.99±1.05 bd ]]>

[0124] Note: a means P<0.05 compared with the blank control group; b means P<0.01 compared with the blank control group; c means P<0.05 compared with the whey protein group; d means P<0.01 compared with the whey protein group.

[0125] Compared with the blank group, there was no significant difference in the levels of LDH, LA, BUN, liver glycogen, muscle glycogen and MDA in the whey protein group (P>0.05); the low-dose Chinese medicine combination group could reduce the levels of LDH, LA, BUN and MDA in mice (P<0.05), and increase the levels of muscle glycogen and liver glycogen in mice (P<0.05). The high-dose Chinese medicine combination group significantly reduced the levels of LDH, LA, BUN and MDA in mice (P<0.01), and significantly increased the levels of muscle glycogen and liver glycogen in mice (P<0.01).

[0126] The experimental results show that the Chinese medicine combination of the present invention can increase the content of liver glycogen and muscle glycogen, reduce the content of LA, BUN and MDA, delay the occurrence of fatigue or accelerate the elimination of fatigue, increase the body's energy storage capacity, and accelerate the elimination of metabolites.

[0127] 3. Comparison of clinical application of drugs

[0128] 1. Selection and grouping of case subjects

[0129] 100 patients with impotence, premature ejaculation, and spermatorrhea were collected and divided into an observation group and a control group by random number table method, with 50 cases in each group. The age of the observation group ranged from 33 to 65 years old, with an average age of (47.7±8.1) years old. The age of the control group ranged from 33 to 64 years old, with an average age of (46.5±8.5) years old. All patients had different degrees of backache, fatigue, dizziness, chills, impotence, premature ejaculation, spermatorrhea, etc. Reproductive tract infection factors and organic diseases were excluded. There was no statistically significant difference in general data such as age and condition between the two groups of patients (P>0.05).

[0130] Control group: Oral administration of Shenbao tablets (manufacturer: Huiren Group, product batch number 2401014), 3 tablets at a time, 3 times a day, for 6 consecutive months, and renal function was reviewed.

[0131] Observation group: took the Chinese medicine composition of the present invention 3 times a day, once in the morning, noon and evening, for 6 consecutive months, and then underwent renal function review.

[0132] 2. Efficacy evaluation

[0133] Significant effect: Clinical symptoms such as low back pain, fatigue, dizziness and chills disappeared, kidney function recovered, impotence and premature ejaculation disappeared, and sexual function was fully restored.

[0134] Effective: Clinical symptoms such as low back pain, fatigue, dizziness and chills have improved, kidney function has improved, impotence and premature ejaculation have decreased, and sexual function has basically recovered.

[0135] Ineffective: Clinical symptoms such as low back pain, fatigue, dizziness and chills did not improve, renal function did not improve, impotence and premature ejaculation still existed, and sexual dysfunction or even loss of sexual function occurred.

[0136] 3 Results

[0137] All patients were observed and recorded for backache, fatigue, dizziness, chills, renal function, impotence, premature ejaculation and other sexual function conditions. The treatment results of the control group and the observation group are shown in Table 7.

[0138] Table 7 Treatment results of the control group and observation group

[0139] Group Number of cases Significant effect efficient invalid Total Effectiveness Observation Group 50 26 20 4 92 Control group 50 17 23 10 80

[0140] As shown in Table 7, the Chinese medicine composition of the present invention has a significant efficacy of 52% and a total efficacy of 92% in improving male sexual function. Compared with the control group, the significant efficacy is increased by 53% and the total efficacy is increased by 15%.

[0141] Case Collection

[0142] Case 1

[0143] Mr. Jia, 55 years old, male, from Shandong Province, was diagnosed with impotence by the hospital in March 2023. The treatment effect in the hospital was not obvious, and he has basically lost his function. He started using the Chinese medicine composition of the present invention in May 2023. After 3 months of treatment, he could have an erection, and after 6 months of use, his function was basically restored.

[0144] Case 2

[0145] Mr. Li, 41 years old, male, from Guangdong Province, suffered from premature ejaculation. The effect of hospital treatment was not obvious. Now he can only maintain it for less than 2 minutes. He started using the Chinese medicine composition of the present invention in May 2023. After 1 month of treatment, he can maintain it for 3-5 minutes. After 4 months of use, his function was basically restored.

[0146] Case 3

[0147] Zhu, 33 years old, male, from Jiangsu Province, was diagnosed by the hospital with a long history of masturbation and severe spermatorrhea. The effects of various treatments were not ideal. After using the Chinese medicine composition of the present invention for one month, his condition began to improve and his functions were basically restored after five months of use.

[0148] Case 4

[0149] Mr. Liu, 59 years old, male, from Dongguan City, was diagnosed with impotence by the hospital in February 2023. The treatment effect of the hospital was not obvious, and he has basically lost his function. He started using the Chinese medicine composition of the present invention in May 2023. After 4 months of treatment, he can have an erection, and after 6 months of use, his function has basically recovered.

[0150] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating male sexual dysfunction and anti-fatigue, characterized in that: In terms of weight, the traditional Chinese medicine composition consists of 15 parts of astragalus, 9 parts of scutellaria, 9 parts of oriental rhizome, 9 parts of salvia miltiorrhiza and 6 parts of ginseng.

2. The use according to claim 1, characterized in that: The male sexual function includes but is not limited to symptoms such as impotence, premature ejaculation, and spermatorrhea.

3. A Chinese medicine composition pharmaceutical preparation, characterized in that: The pharmaceutical preparation consists of the Chinese medicine composition according to claim 1 and pharmaceutically acceptable excipients.

4. The Chinese medicine composition pharmaceutical preparation according to claim 3, characterized in that: The Chinese medicine composition pharmaceutical preparation is a kind of capsule, tablet, granule, mixture, pill, dripping pill, effervescent tablet, syrup, oral liquid, powder, granule, freeze-dried powder injection and injection.

5. The Chinese medicine composition pharmaceutical preparation according to claim 4, characterized in that: The Chinese medicine composition preparation is a granule.

6. The Chinese medicine composition pharmaceutical preparation according to claim 5, characterized in that: The granules are prepared from the Chinese medicine composition according to claim 1 and pharmaceutically acceptable excipients in a weight ratio of 1:1.5 to 8.5; preferably, the weight ratio is 1:2.0 to 5.

5.

7. The Chinese medicine composition pharmaceutical preparation according to claim 6, characterized in that: The pharmaceutically acceptable excipients of the granules include fillers and binders, wherein the fillers are one or more of mannitol, lactose, sorbitol, sucrose, and cyclodextrin; and the binders are one or more of 3% PVP in 75% ethanol solution, 3% hydroxypropyl methylcellulose in 50% ethanol solution, 10% povidone K30 in aqueous solution, and 30% starch slurry.

8. The Chinese medicine composition pharmaceutical preparation according to claim 7, characterized in that: The filler is a mixture of cyclodextrin and sorbitol; calculated by weight ratio, the ratio of cyclodextrin to sorbitol is 1:0.5-1.

4.

9. The Chinese medicine composition pharmaceutical preparation according to claim 8, characterized in that: The cyclodextrin is hydroxypropyl-β-cyclodextrin.

10. The Chinese medicine composition pharmaceutical preparation according to claim 5, characterized in that: The preparation method of the pharmaceutical preparation is: (1) Grind ginseng and sieve it into fine powder for later use; (2) Weighing astragalus, scutellaria, and orientalis according to the ratio, soaking in water, boiling, filtering, and concentrating to obtain a concentrated solution; (3) weighing Salvia miltiorrhiza according to the ratio, removing impurities, washing, drying, grinding and sieving to obtain fine powder; (4) combining the fine powder obtained in the above step (1) and the concentrated solution obtained in step (2), mixing them evenly, concentrating them into a thick paste, drying them under reduced pressure, crushing them, sieving them, and mixing them with the fine powder obtained in step (3) to obtain a Chinese medicine composition; (5) The Chinese medicine composition of step (4) is mixed evenly with the filler, and then mixed with a binder to form granules, thereby obtaining a Chinese medicine composition pharmaceutical preparation.

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