A pharmaceutical composition with the effects of preventing seminal emission and tonifying kidney, preparation and application thereof

Abstract

This invention discloses a pharmaceutical composition with the function of tonifying the kidneys and strengthening essence, its preparation and application, belonging to the field of pharmaceutical composition technology. The pharmaceutical composition contains rehmannia glycoside A, echinacoside, cornus glycoside I, ursolic acid, coumaric acid, scopolamine, quercetin-3-O-β-D-xylanopyranoside, catechin-7-O-β-D-glucopyranoside, β-sitosterol, hyperoside, kaempferol-3-O-robinoside, and calamus spirone. This invention contains 34 active ingredients, including bergamot lactone, vanillic acid, N-acetyl-L-phenylalanine, quassinolide, acacia extract, Rosa laevigata polysaccharide, pachymic acid, pachymic polysaccharide, ginsenoside IV, oleanolic acid, pentoxymethylfurfural, scopolamine, genipin, eucommia ulmoides alcohol, pinoresinol diglucoside, crystal blue glycoside, verbascoside, and lysine. Compared to traditional kidney-tonifying and sperm-strengthening pills, this invention uses less dosage and has a better effect on improving sperm count and motility.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical composition technology, and more specifically, to a pharmaceutical composition having the effect of strengthening the kidneys and tonifying essence, its preparation and application. Background Technology

[0002] Gujing Bushen Wan is a commercially available traditional Chinese medicine. Its main ingredients are Rehmannia glutinosa, Cornus officinalis, Lycium barbarum, Schisandra chinensis, Rubus idaeus, Acorus tatarinowii, Dioscorea opposita, Rosa laevigata, Poria cocos, Achyranthes bidentata, Foeniculum vulgare, Eucommia ulmoides, Morinda officinalis, Cistanche deserticola, Polygala tenuifolia, Cuscuta chinensis, and Glycyrrhiza uralensis. The excipients are sucrose and rice flour. It has the effect of warming and tonifying the spleen and kidneys. Clinically, it is used to treat symptoms such as spleen and kidney deficiency and cold, loss of appetite, fatigue, lower back pain, premature ejaculation, and nocturnal emission.

[0003] In recent years, extensive research has been conducted both domestically and internationally on the chemical composition, pharmacological effects, and applications of traditional Chinese medicine (TCM). TCM active ingredients have become an important pathway for new drug development. It is of great significance to develop a drug composition with better effects on strengthening the kidneys and consolidating essence based on traditional prescriptions. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a pharmaceutical composition with the function of strengthening essence and tonifying the kidneys, as well as its preparation and application.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A pharmaceutical composition with the function of strengthening essence and tonifying the kidney, wherein the active ingredients of the pharmaceutical composition are derived from Rehmannia glutinosa (processed), Cornus officinalis, Lycium barbarum, Schisandra chinensis, Rubus idaeus, Acorus tatarinowii, Dioscorea opposita, Rosa laevigata, Poria cocos, Achyranthes bidentata, Foeniculum vulgare, Eucommia ulmoides, Morinda officinalis, Cistanche deserticola, Polygala tenuifolia, and Cuscuta chinensis; specifically including the following active ingredients: rehmannia glycoside A, echinacoside, cornus officinalis glycoside I, ursolic acid, coumaric acid, hyoscyamine, quercetin-3-O-β-D-xylanopyranoside, catechin-7-O-β-D-glucopyranoside, β-Sitosterol, hyperoside, kaempferol-3-O-robinin, calamus spirulina, bergamot lactone, vanillic acid, N-acetyl-L-phenylalanine, quassin, acacia extract, Rosa laevigata polysaccharide, methyl pachylate, pachymic polysaccharide, ginsenoside IV, oleanolic acid, pent-hydroxymethylfurfural, scopolamine, genipin, eucommia alcohol, pinoresinol diglucoside, crystalloidin, verbascoside, lysine, 3,4,5-trimethoxycinnamic acid, polygala tenuifolia saponin, matrine, and chlorogenic acid.

[0007] In some embodiments, the mass ratio of echinacoside, hyperoside, calamus spirone, and ginsenoside IV is 10-15:5-10:1-5:10-15. Preferably, the mass ratio of echinacoside, hyperoside, calamus spirone, and ginsenoside IV is 12:6:4:13.

[0008] In other embodiments, the pharmaceutical composition, by weight, comprises the following active ingredients: 1-6 parts of rehmannia glycoside A, 10-15 parts of echinacoside, 0.5-1 part of cornus glycoside I, 1-5 parts of ursolic acid, 1-5 parts of coumaric acid, 0.5-1 part of hyoscyamine, 0.5-1 part of quercetin-3-O-β-D-xylanopyranoside, 3-8 parts of catechin-7-O-β-D-glucopyranoside, 0.5-1 part of β-sitosterol, 5-10 parts of hyperoside, 1-5 parts of kaempferol-3-O-robinoside, 1-5 parts of calamispirone, 0.5-1 part of bergapten, 0.5-1 part of vanillic acid, 0.5-1 part of N-acetyl-L-phenylalanine, 0.5-1 part of quassinolide, 0.5-1 part of acacia extract, and 0.5-1 part of Rosa laevigata. Polysaccharide 3-8 parts, pachymic acid 1-5 parts, poria polysaccharide 5-10 parts, ginsenoside IV 10-15 parts, oleanolic acid 0.5-1 part, pent-hydroxymethylfurfural 0.5-1 part, scopolamine 0.5-1 part, genipin glycoside 0.5-1 part, eucommia alcohol 0.5-1 part, pinoresinol diglucoside 0.5-1 part, crystallizing blue glycoside 1-5 parts, verbascoside 0.5-1 part, lysine 0.5-1 part, 3,4,5-trimethoxycinnamic acid 0.5-1 part, polygala saponin 0.5-1 part, matrine 0.5-1 part, and chlorogenic acid 0.5-1 part.

[0009] Preferably, the pharmaceutical composition comprises, by weight, the following active ingredients:

[0010] Rehmannia glutinosa A 4 parts, echinacoside 12 parts, cornus officinalis glycoside I 0.8 parts, ursolic acid 3 parts, coumaric acid 2 parts, hyoscyamine 0.8 parts, quercetin-3-O-β-D-xylopyranoside 0.8 parts, catechin-7-O-β-D-glucopyranoside 5 parts, β-sitosterol 0.8 parts, hyperoside 6 parts, kaempferol-3-O-robinin 3 parts, calamispirone 4 parts, bergapten 0.8 parts, vanillic acid 0.6 parts, N-acetyl-L-phenylalanine 0.8 parts, quassinolide 0.8 parts, acaciatin 0.8 parts. The following ingredients were found in the following composition: 5 parts of Rosa laevigata polysaccharide, 3 parts of pachymic acid, 8 parts of pachymic polysaccharide, 13 parts of ginsenoside IV, 0.8 parts of oleanolic acid, 0.8 parts of pent-hydroxymethylfurfural, 0.8 parts of scopolamine, 0.8 parts of genipin, 0.8 parts of eucommia ulmoides alcohol, 0.8 parts of pinoresinol diglucoside, 2 parts of crystallizing blue glycoside, 0.8 parts of verbascoside, 0.8 parts of lysine, 0.8 parts of 3,4,5-trimethoxycinnamic acid, 0.8 parts of Polygala tenuifolia saponin, 0.8 parts of matrine, and 0.8 parts of chlorogenic acid.

[0011] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, which includes mixing the active ingredients in the prescribed amounts, grinding and sieving them.

[0012] Preferably, the sieving is performed through an 80-120 mesh sieve.

[0013] The present invention also provides the use of the above-mentioned pharmaceutical composition in the preparation of a preparation for strengthening the kidneys and tonifying the essence.

[0014] Preferably, the preparation is a pill, granule, capsule, tablet, suspension or oral liquid.

[0015] The present invention also provides a preparation for strengthening the kidneys and enhancing sexual function, comprising the above-mentioned pharmaceutical composition and pharmaceutically acceptable excipients.

[0016] The beneficial effects of this invention are as follows:

[0017] (1) Based on the original kidney-tonifying and essence-strengthening pill, this invention selects the active ingredients from Rehmannia glutinosa (processed), including rehmannia glutinosa glycoside A and echinacoside; Cornus officinalis (active ingredients) including cornus officinalis glycoside I and ursolic acid; Lycium barbarum (active ingredients) including coumaric acid and scopolamine; Schisandra chinensis (active ingredients) including quercetin-3-O-β-D-xylopyranoside and catechin-7-O-β-D-glucopyranoside; Rubus idaeus (active ingredients) including β-sitosterol, hyperoside, and kaempferol-3-O-robinin; Acorus tatarinowii (active ingredients) including acorus spirulinaone, bergapten, and vanillic acid; Dioscorea opposita (active ingredients) including N-acetyl-L-phenylalanine, quassinolide, and acaciain; and Rosa laevigata (active ingredient) including Rosa laevigata polysaccharide. The active ingredients of this invention, namely poria cocos acid and poria cocos polysaccharide from Poria cocos, bamboo ginsenoside IV and oleanolic acid from Achyranthes bidentata, pent-hydroxymethylfurfural and scopolamine from Fennel, genipinic acid, eucommia ulmoides alcohol and pinoresinol diglucoside from Eucommia ulmoides, crystalloidin from Morinda officinalis, verbascoside and lysine from Cistanche deserticola, 3,4,5-trimethoxycinnamic acid and polygala tenuifolia saponin from Polygala tenuifolia, and matrine and chlorogenic acid from Cuscuta chinensis, are combined to obtain the pharmaceutical composition of this invention. Compared with the traditional kidney-tonifying and sperm-strengthening pill, this invention requires less dosage, has better effects on improving sperm count and motility, and has clearly defined components and superior safety.

[0018] (2) Meanwhile, it was unexpectedly discovered that when the mass ratio of echinacoside, hyperoside, calamus spirulinaone and ginsenoside IV was 10-15:5-10:1-5:10-15, the prepared drug composition had a better anti-fatigue effect. Detailed Implementation

[0019] The following description of the embodiments is merely to aid in understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the scope of the claims. The following description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not limited to the embodiments shown herein, but can be applied to a wider scope consistent with the principles and novel features disclosed herein. While any methods and materials similar to or equivalent to those described herein may be used in the implementation or testing of the present invention, preferred methods and materials are listed herein.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0021] The active ingredients used in the embodiments of this invention are all commercially available products that meet food-grade or pharmaceutical-grade standards. Purchase information is shown in Table 1.

[0022] Table 1 Information on active ingredients

[0023]

[0024] Example 1: A pharmaceutical composition for strengthening essence and tonifying the kidneys

[0025] The active ingredients of the pharmaceutical composition are shown in Table 2.

[0026] Table 2 Formulation of the pharmaceutical composition described in Example 1

[0027]

[0028] The preparation method of the above-mentioned pharmaceutical composition is as follows: mix the active ingredients in the prescribed amount and grind them through a 100-mesh sieve.

[0029] Example 2: A pharmaceutical composition for strengthening essence and tonifying the kidneys

[0030] The active ingredients of the pharmaceutical composition are shown in Table 3.

[0031] Table 3 Formulation of the pharmaceutical composition described in Example 2

[0032]

[0033]

[0034] The preparation method is the same as in Example 1.

[0035] Example 3: A pharmaceutical composition for strengthening essence and tonifying the kidneys

[0036] The active ingredients of the pharmaceutical composition are shown in Table 4.

[0037] Table 4 Formulation of the pharmaceutical composition described in Example 3

[0038]

[0039]

[0040] The preparation method is the same as in Example 1.

[0041] Comparative Example: A pharmaceutical composition for strengthening sperm and tonifying the kidneys

[0042] The only difference between this comparative example and Example 3 is that the mass ratio of echinacoside, hyperoside, calamus spirulinaone, and ginsenoside IV is 1:4:2:4.

[0043] Specifically, the pharmaceutical composition comprises 5 parts by weight of echinacoside, 20 parts by weight of hyperoside, 10 parts by weight of calamus spirulinaone, and 20 parts by weight of ginsenoside IV.

[0044] I. Anti-fatigue test in mice:

[0045] 1.1 Laboratory Animals

[0046] SPF-grade Kunming mice, male, weighing 18-22g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0047] 1.2 Animal grouping and administration

[0048] Mice were randomly divided into 6 groups according to body weight: normal control group, drug groups 1-3, comparative group, and Gujing Bushen pill group, with 10 mice in each group. Drug groups 1, 2, and 3 were administered the drug compositions prepared in the corresponding examples 1, 2, and 3 by gavage. The control group was administered the drug composition prepared in the comparative example by gavage at a dose of 30 mg / kg. The Gujing Bushen pill group was administered Gujing Bushen pill (commercially available) by gavage at a dose of 600 mg crude drug / kg once daily. The normal control group was administered an equal volume of distilled water by gavage. The administration was continued for 20 days.

[0049] 1.3 Experimental Methods:

[0050] Weighted swimming experiment: 30 minutes after the last gavage administration, the mice were loaded with lead sheets with 5% of their body weight on their tails and placed in a swimming tank with a water depth of 35 cm and a water temperature of 25 ± 1 ℃. The time from the start of swimming to death was recorded as the weighted swimming time of the mice.

[0051] 1.4 Data Processing and Statistical Analysis

[0052] Data were statistically analyzed using SPSS 25.0 software. Experimental results are expressed as mean ± standard error. Pairwise comparisons of means among multiple experimental groups and one control group were used for statistical analysis. For non-normal or unequal variance data, appropriate variable transformations were performed until the data met the requirements of normality or homogeneity of variance before statistical analysis. If normality or homogeneity of variance was still not achieved after variable transformation, the rank-sum test was used for statistical analysis. A p-value < 0.05 was considered statistically significant.

[0053] 1.5 Test Results

[0054] Table 5

[0055] Group Animals / only Weighted swimming time / min normal control group 10 55.8±14.2 Example Group 1 10 79.8±12.9*# Example Group 2 10 81.1±13.0*# Example Group 3 10 85.8±13.9**## Comparative group 10 60.7±16.4 Kidney-tonifying and sperm-strengthening pills 10 78.2±15.8*#

[0056] Compared with the normal control group, *P<0.05, indicating a significant difference, and **P<0.01, indicating a highly significant difference; compared with the comparative control group, #P<0.05, indicating a significant difference, and ##P<0.01, indicating a highly significant difference.

[0057] As shown in Table 5, compared with the normal control group, the weight-bearing swimming time of mice in Example Groups 1, 2, and 3, as well as the Gujing Bushen Pill group, were significantly different, indicating that the drug composition of the present invention and Gujing Bushen Pill can significantly prolong the weight-bearing swimming time of mice. At the same time, the weight-bearing swimming time of mice in the comparative group was significantly different from that in Example Groups 1, 2, and 3, indicating that the drug compositions prepared in Examples 1, 2, and 3 of the present invention have better anti-fatigue effects than the drug compositions prepared in the comparative group.

[0058] II. Testing for Improving Sperm Quality in Mice

[0059] 2.1 Laboratory Animals

[0060] SPF-grade Kunming mice, adult males, weighing 18-22g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0061] 2.2 Animal grouping and administration

[0062] Mice were randomly divided into 7 groups according to body weight: normal control group, model group, drug groups 1-3, comparative group, and Gujing Bushen Wan group, with 10 mice in each group. Except for the normal control group, all other groups of mice were administered gossypol acetate (Redixin) 50 mg / kg by gavage once a day for 5 consecutive days. After the 6th day, drug groups 1, 2, and 3 were administered the drug compositions prepared in the corresponding examples 1, 2, and 3 by gavage, respectively. The control group was administered the drug composition prepared in the comparative example by gavage at a dose of 60 mg / kg. The Gujing Bushen Wan group was administered Gujing Bushen Wan (commercially available) by gavage at a dose of 600 mg / kg once a day. The normal control group and the model group were administered an equal volume of distilled water by gavage. All treatments were carried out for 20 consecutive days.

[0063] 2.3 Experimental Methods

[0064] Thirty minutes after the last gavage administration, the mice were euthanized by cervical dislocation, and the epididymal tails from both sides were quickly removed and placed in centrifuge tubes containing BWW culture medium for sperm cells (purchased from Shanghai Chuangsai Technology Co., Ltd., catalog number PM20205). The temperature of the BWW culture medium for sperm cells was 37°C and the volume was 0.3 mL. The epididymal tails were cut into pieces and incubated at 37°C for 5 minutes to allow the sperm to swim out, which was then used as a semen sample.

[0065] 2.4 Data Processing and Statistical Analysis

[0066] SPSS 25.0 software was used for statistical analysis. Experimental data are expressed as mean ± standard error (mean ± SEM). Pairwise comparisons of means among multiple experimental groups and one control group were performed. For non-normal or unequal variance data, appropriate variable transformations were performed until the data met the requirements of normality or homogeneity of variance before statistical analysis. If the transformations still did not achieve normality or homogeneity of variance, the rank-sum test was used for statistical analysis. P < 0.05 was considered statistically significant.

[0067] 2.5 Results

[0068] Sperm quality was analyzed in semen samples using a fully automated sperm analyzer, and the results are shown in Table 6.

[0069] Table 6

[0070]

[0071] Compared with the normal control group, **P<0.01 indicates a significant difference in the model group; compared with the model group, #P<0.05 indicates a significant difference, and ##P<0.01 indicates a highly significant difference; compared with the control group, ΔP<0.05 indicates a significant difference, and ΔΔP<0.01 indicates a highly significant difference; compared with the Gujing Bushen Wan group, ▲P<0.05 indicates a significant difference.

[0072] Table 6 shows that, compared with the normal control group, the total sperm count and motile sperm count in the model group were significantly different, indicating that the modeling was successful. Compared with the model group and the comparative group, the total sperm count and motile sperm count in Example Groups 1, 2, and 3, as well as the Gujing Bushen Pill group, were significantly different, indicating that the pharmaceutical composition of the present invention and the Gujing Bushen Pill can increase the sperm count and sperm motility in mice, while the pharmaceutical composition prepared in the comparative group did not have the effect of increasing the sperm count and sperm motility in mice.

[0073] Meanwhile, compared with the Gujing Bushen pill group, the total sperm count and motile sperm count of Example groups 1, 2 and 3 all showed significant differences, indicating that the pharmaceutical composition prepared in this invention has a better effect on improving sperm count and sperm motility in mice than the Gujing Bushen pill.

[0074] The above description, in conjunction with specific embodiments, further illustrates the present invention. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. Those skilled in the art should understand that modifications or substitutions to the details and form of the technical solutions of the present invention can be made without departing from the spirit and scope of the invention, and all such modifications and substitutions fall within the protection scope of the present invention.

Claims

1. A pharmaceutical composition having the effect of strengthening essence and tonifying the kidneys, wherein the active ingredients of the pharmaceutical composition are derived from Rehmannia glutinosa (processed), Cornus officinalis, Lycium barbarum, Schisandra chinensis, Rubus idaeus, Acorus tatarinowii, Dioscorea opposita, Rosa laevigata, Poria cocos, Achyranthes bidentata, Foeniculum vulgare, Eucommia ulmoides, Morinda officinalis, Cistanche deserticola, Polygala tenuifolia, and Cuscuta chinensis, characterized in that, Based on parts by weight, it consists of the following active ingredients: Rehmannia glutinosa A 1-6 parts, Echinacoside 10-15 parts, Cornus officinalis glycoside I 0.5-1 part, ursolic acid 1-5 parts, coumaric acid 1-5 parts, hyoscyamine 0.5-1 part, quercetin-3-O-β-D-xylopyranoside 0.5-1 part, catechin-7-O-β-D-glucopyranoside 3-8 parts, β-sitosterol 0.5-1 part, hyperoside 5-10 parts, kaempferol-3-O-robinoside 1-5 parts, calamus spirulinaone 1-5 parts, bergamot lactone 0.5-1 part, vanillic acid 0.5-1 part, N-acetyl-L-phenylalanine 0.5-1 part, quassrol lactone 0.5-1 part, acacia 0.5-1 part, Rosa laevigata polysaccharide 3-8 parts, pachymic acid 1-5 parts, poria polysaccharide 5-10 parts, bamboo ginsenoside IV 10-15 parts, oleanolic acid 0.5-1 part, pent-hydroxymethylfurfural 0.5-1 part, scopolamine 0.5-1 part, genipin glycoside 0.5-1 part, eucommia ulmoides alcohol 0.5-1 part, pinoresinol diglucoside 0.5-1 part, crystal blue glycoside 1-5 parts, verbascoside 0.5-1 part, lysine 0.5-1 part, 3,4,5-trimethoxycinnamic acid 0.5-1 part, polygala root saponin 0.5-1 part, matrine 0.5-1 part, and chlorogenic acid 0.5-1 part; Furthermore, the mass ratio of echinacoside, hyperoside, calamus spirulinaone, and ginsenoside IV is 10-15:5-10:1-5:10-15.

2. The pharmaceutical composition according to claim 1, characterized in that, The mass ratio of echinacoside, hyperoside, calamus spirulinaone, and ginsenoside IV is 12:6:4:

13.

3. The pharmaceutical composition according to claim 1, characterized in that, The product, by weight, is composed of the following active ingredients: Rehmannia glutinosa A 4 parts, Echinacoside 12 parts, Cornus officinalis glycoside I 0.8 parts, Ursolic acid 3 parts, Coumaric acid 2 parts, Scopolamine 0.8 parts, Quercetin-3-O-β-D-xylopyranoside 0.8 parts, Catechin-7-O-β-D-glucopyranoside 5 parts, β-sitosterol 0.8 parts, Hyperoside 6 parts, Kaempferol-3-O-robinin 3 parts, Acorus tatarinowii 4 parts, Bergamotrol 0.8 parts, Vanillic acid 0.6 parts, N-acetyl-L-phenylalanine 0.8 parts, Magnolia lactone I 0.8 parts, Acaciatin 0.8 parts, Rosa laevigata polysaccharide 5 parts, Poria cocos acid 3 parts, Poria cocos polysaccharide 8 parts, and Bambusa textilis saponin IV. 13 parts, oleanolic acid 0.8 parts, pent-hydroxymethylfurfural 0.8 parts, scopolamine 0.8 parts, genipin glycoside 0.8 parts, eucommia ulmoides alcohol 0.8 parts, pinoresinol diglucoside 0.8 parts, crystal blue glycoside 2 parts, verbascoside 0.8 parts, lysine 0.8 parts, 3,4,5-trimethoxycinnamic acid 0.8 parts, polygala tenuifolia saponin 0.8 parts, matrine 0.8 parts, and chlorogenic acid 0.8 parts.

4. A method for preparing the pharmaceutical composition according to any one of claims 1-3, characterized in that, The process includes the following steps: mix the active ingredients in the prescribed amount, grind and sieve.

5. The use of the pharmaceutical composition according to any one of claims 1-3 in the preparation of a preparation for strengthening the kidneys and tonifying the essence.

6. The application according to claim 5, characterized in that, The preparation is a pill, granule, capsule, tablet, suspension or oral liquid.

7. A preparation for strengthening essence and tonifying the kidneys, characterized in that, The pharmaceutical composition according to any one of claims 1-3 and a pharmaceutically acceptable excipient.

Images