Application of Hypocaplin A in preparation of medicine for improving reproductive injury of male mammals and improving quality of normal male seminal fluid
By using Hypocrellin A as the active ingredient, the unknown problems of Hypocrellin A in the prior art in improving male semen quality were solved, and the effect of significantly improving male reproductive damage and improving normal male semen quality was achieved. The drug was safe and reliable, with good development value and application prospects.
Patent Information
- Application Number
- CN202510448424.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-10
- Publication Date
- 2025-06-27
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The efficacy of Hypocrellin A in improving or improving male reproductive capacity (sperm quality) has not been clarified in the prior art, and no reports have been made about Hypocrellin A in improving male semen quality.
Drugs that use Hypocrellin A as the active ingredient are significantly improved male reproductive damage and improved the quality of normal male semen through various forms of existence (such as solutions, suspensions, lyophilized powder injections, emulsions, pills, capsules, powders, controlled release, sustained release preparations and microsomes, etc.).
Hypocrellin A can significantly improve male reproductive damage and improve the quality of normal male semen. The drug itself and drug concentration are safe and reliable, with good development value and application prospects.
Smart Images
Figure CN120204183A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technologies, and in particular to the application of Hypocrellin A in the preparation of drugs for improving reproductive damage of male mammals and enhancing the semen quality of normal males. Background Art
[0002] Chemotherapy, environmental pollution, work pressure, problem foods, etc. in the current era have increasingly and commonly affected male reproductive ability (semen quality). Natural compounds are an important treasure trove beneficial to solving human health problems. There have been numerous reports indicating that various natural compounds such as Hypocrellin A, paclitaxel, berberine, and berberine hydrochloride are used to treat diseases. Among them, Hypocrellin A is a compound isolated from Shiraia bambusicola, and is one of the main components of Shiraia bambusicola. The molecular formula of Hypocrellin A is C 30 H 26 O 10 , and its chemical name is: 1H-Cyclohepta[ghi]perylene-5,12-dione,1-acetyl-2,3-dihydro-2,6,11-trihydroxy-4,8,9,13-tetramethyl. Modern pharmacological studies have shown that Hypocrellin A in Pueraria lobata has anti-inflammatory and antioxidant functions; can dilate blood vessels, lower blood pressure, and improve microcirculation; has a good protective effect on kidney-related disease models; and has obvious regulatory effects on non-specific immunity, humoral immunity, and cellular immunity. At present, the efficacy of Hypocrellin A in enhancing or improving male reproductive ability (semen quality) is still unclear, and there have been no reports on products of Hypocrellin A in improving male semen quality. Summary of the Invention
[0003] The purpose of the present invention is to solve the deficiencies existing in the prior art, and to propose the application of Hypocrellin A in the preparation of drugs for improving reproductive damage of male mammals and enhancing the semen quality of normal males. Using this Hypocrellin A can significantly improve male reproductive damage and significantly enhance the semen quality of normal male animals, and has good development value and application prospects.
[0004] In order to achieve the above purpose, the present invention adopts the following technical solution:
[0005] The application of Hypocrellin A in the preparation of drugs for improving reproductive damage of male mammals (including humans).
[0006] Use of hypocrellin A in the preparation of a medicament for improving the semen quality of normal male mammals (including humans).
[0007] Herein, the reproductive ability refers to semen quality (such as sperm concentration and motility), and reproductive damage refers to the low semen quality caused by various physical and chemical factors such as drugs. Normal male mammals (including humans) refer to ordinary male individuals without medical reproductive disorders or other diseases.
[0008] Preferably, the molecular general formula of the hypocrellin A is:
[0009]
[0010] Preferably, the medicament is administered via oral, intravenous, arterial and other administration routes in various forms such as solution, suspension, freeze-dried powder injection, emulsion, pill, capsule, powder, controlled release, sustained release preparation and microsome.
[0011] Herein, the medicament includes products such as oral liquids, injections, health products, etc. that contain hypocrellin A as long as they can improve or enhance semen quality, and are present and administered in the above forms and routes.
[0012] By adopting the above technical solution: the effects of hypocrellin A on the body weight, testis weight and semen-related indexes related to reproductive damage of normal healthy pubertal male ICR mice and adult male ICR mice treated with busulfan were detected. Among them, the changes in the body weight and testis weight of experimental animals were observed by photographing and weighing; the CASA system (computer-aided sperm analysis system) was used to detect the relevant indexes of the semen quality of experimental animals. Based on this, the effect of hypocrellin A on the semen quality of male mammals was judged.
[0013] Among them, a tiny dose of Hypocrellin A can significantly enhance and improve the spermatogenic function of male mammals (including humans), improve semen quality, and both the drug itself and its concentration are safe and reliable. The present invention relates to the application of a drug with Hypocrellin A as the active ingredient in products for improving reproductive damage in male mammals and enhancing the semen quality of normal males. The drug with Hypocrellin A as the active ingredient can be prepared according to methods well-known in the art, or by combining the product of the present invention with Hypocrellin A as the active ingredient with one or more pharmaceutically acceptable solid or liquid excipients / adjuvants to form any dosage form suitable for use by male mammals (including humans). Depending on the individual conditions of patients or animals, there are wide variations in the administration route, dosage form, etc. of Hypocrellin A. For example, the content of the drug with Hypocrellin A as the active ingredient in the appropriate daily dose for normal healthy male ICR mice of the present invention is usually 0.001 mg / kg to 200 mg / kg body weight, preferably 50 mg / kg to 200 mg / kg body weight. In the ICR male mice with low semen quality caused by various physical and chemical factors such as drugs, the content of the drug with Hypocrellin A as the active ingredient in the appropriate daily dose is usually administered at 0.001 mg / kg to 100 mg / kg body weight, and the dose of Hypocrellin A is preferably 100 mg / kg body weight per day. The dosage for humans and other mammals can be obtained according to conversion formulas such as the surface area of humans and animals. The above dosage can be administered in one dosage unit or divided into several dosage units, which depends on the doctor's clinical experience and the dosing regimen including the use of other treatment means. The drug with Hypocrellin A as the active ingredient of the present invention can be taken alone or in combination with other therapeutic drugs or symptomatic drugs. When there is a synergistic effect between the drug with Hypocrellin A as the active ingredient and other therapeutic drugs, its dosage should be adjusted according to the actual situation.
[0014] Compared with the prior art, the present invention has the following beneficial effects:
[0015] 1. The drug with Hypocrellin A as the active ingredient of the present invention can improve reproductive damage in male mammals (including humans) and enhance the semen quality of normal males. This use is publicly disclosed for the first time, which broadens the application field of Hypocrellin A.
[0016] 2. The present invention publicly discloses for the first time that preparing a drug with Hypocrellin A can improve reproductive damage in male mammals (including humans) and enhance the semen quality of normal males.
[0017] 3. The present invention can achieve the improvement of reproductive damage in male mammals (including humans) and the enhancement of semen quality in normal males by preparing drugs with a small dose of Hypocrellin A. The drugs are safe and reliable, and have good prospects for transformation and clinical application when developed as products. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 It is the effect diagram of Hypocrellin A enhancing the semen quality of pubertal ICR mice in Example 1 of the present invention; Normal represents the group of normal and healthy mice, and 50 mg / kg or 200 mg / kg means administering 50 mg or 200 mg of Hypocrellin A per kilogram of mouse body weight;
[0019] Among them, Figure 1 A: The size of the mouse testis (photographed); Figure 1 B: Testis mass index and wet weight of bilateral testes, ns represents no statistical significance; Figure 1 C: The CASA results show that the semen quality of Hypocrellin A-administered mice at 50 mg / kg body weight and 200 mg / kg body weight is significantly higher than that of normal mice. # P < 0.05, ## P < 0.01, ### P < 0.001 represents statistical significance, and ns represents no statistical significance.
[0020] Figure 2 It is the effect diagram of Hypocrellin A significantly improving the reproductive damage of mice in the busulfan model group in Example 2 of the present invention; Normal (control group of normal and healthy mice), Busulfan (busulfan), Hypocrellin A (Hypocrellin A), 100 mg / kg means administering 100 mg of Hypocrellin A per kilogram of mouse body weight;
[0021] Among them, Figure 2 A: The size of the testis tissue (photographed); Figure 2 B: Testis mass index and wet weight of bilateral testes. # P < 0.05, ## P < 0.01, ### P < 0.001 represents statistical significance, and ns represents no statistical significance; Figure 2 C: The CASA detection results show that Hypocrellin A can significantly improve semen quality indexes such as sperm concentration and sperm motility rate in the model group mice. # P < 0.05, ## P < 0.01, ###P < 0.001 represents statistical significance, and ns represents no statistical significance. The results showed that the sperm concentration and sperm motility of the mice in the busulfan model group were significantly decreased, while the administration of Hypocrellin A at 100 mg / kg body weight significantly improved the sperm concentration and motility of the busulfan model mice. Detailed implementation manners
[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, and thus make a clearer definition of the protection scope of the present invention. The embodiments described in the present invention are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.
[0023] Example 1: Hypocrellin A improves the semen quality of normal pubertal ICR mice
[0024] 1.1 Experimental method
[0025] 1.1.1 Intragastric administration of Hypocrellin A to pubertal model animals
[0026] Three-week-old pubertal ICR male mice were purchased from the Model Animal Research Institute of Nanjing University and randomly divided into 3 groups, with 5 mice in each group. All animals were housed in an SPF-class animal house. The animals were raised in an environment with a constant temperature of 23 ± 2 °C, a humidity of 40 ± 10%, and a 12-hour day-night cycle, and the feed used was ordinary irradiated feed (AIN-93). In the experiment, Hypocrellin A was intragastrically administered to 3-week-old mice at a daily fixed dose of 50 mg Hypocrellin A / kg body weight and 200 mg Hypocrellin A / kg body weight for 10 consecutive days; the mice in the negative control group were intragastrically administered an equal amount of normal saline for 10 consecutive days. During the subsequent feeding period, the mice were allowed to drink distilled water freely, and the mice were sacrificed by cervical dislocation on the 30th day. The body weight, testis size, and testis weight of the mice were measured; and the testes were made into paraffin sections, and the testis sections were stained with PAS; the quality parameters of semen were detected by CASA, and based on this, the promoting effect of Hypocrellin A on the spermatogenic function and semen quality (sperm concentration and motility, etc.) of mice was evaluated.
[0027] 1.1.2 Macroscopic morphological observation
[0028] After sacrificing the mice, their body weights were measured. Then, the abdominal areas of the mice were disinfected with 75% alcohol, and their testes were removed. The surrounding adipose tissue was dissected to obtain pure bilateral mouse testes, which were photographed, weighed, and recorded. The calculation formula for the testicular mass index is: testicular mass index = testicular weight (mg) / body weight (g) × 100%.
[0029] 1.1.3 CASA detection of semen indicators
[0030] Under anesthesia, the corpus epididymidis of the mice was excised, and the bilateral cauda epididymidis was placed in 2 mL of warm (37 °C) HBSS buffer solution (Hank's balanced salt buffer solution) with a pH of 7.4 and incubated for 20 min. The whole process was gently shaken on a shaker to allow the sperm to swim out. 100 μL of the suspension was added to 400 μL of HBSS for dilution. The diluted sperm suspension was dropped on a glass slide, and then a CASA system was used to calculate sperm concentration, motility, and other indicators.
[0031] 1.2 Experimental results
[0032] After continuous intragastric administration of Hypocrellin A to the above-mentioned pubertal ICR mice for 10 days, it was shown that intragastric administration of Hypocrellin A at 50 mg / kg body weight and 200 mg / kg body weight could significantly improve the spermatogenic function and semen quality of male animals. Photographs of the bilateral mouse testes showed that compared with the normal and healthy mice in the control group, the testicular volume of the mice administered with Hypocrellin A at 200 mg / kg body weight was slightly increased, and the testicular mass index was slightly increased; compared with the normal mice in the control group, there was no statistical difference in the testicular mass index between the mice in the 50 mg / kg body weight and 200 mg / kg body weight administration groups ( Figure 1 A and B). The CASA results showed that administration of Hypocrellin A at 50 mg / kg body weight and 200 mg / kg body weight could significantly increase the semen quality (sperm concentration and motility) of the mice compared with normal and healthy mice. Among them, administration of Hypocrellin A at 50 mg / kg body weight increased the semen concentration of the mice by 51.0% compared with normal and healthy pubertal mice, and administration of Hypocrellin A at 200 mg / kg body weight increased the semen concentration of the mice by 51.9% compared with normal and healthy pubertal mice ( Figure 1 C). At the same time, the CASA results also showed that administration of Hypocrellin A at 50 mg / kg body weight and 200 mg / kg body weight could significantly improve the sperm motility of normal pubertal mice( Figure 1C). In addition, the CASA detection results showed that Hypocrellin A could also increase the swimming speed, forward motility, average path velocity (VAP), curvilinear velocity (VCL), straight-line velocity (VSL), amplitude of lateral head displacement (ALH), beat cross frequency (BCF), STR (sperm forward motility), linearity (LIN) of sperm, etc.
[0033] Example 2: Hypocrellin A Improves Reproductive Injury in Mice
[0034] 2.1 Experimental method:
[0035] 2.1.1 Establishment of a reproductive injury model in adult ICR mice induced by busulfan and intragastric administration of Hypocrellin A
[0036] Adult ICR male mice at 8 weeks old were purchased from the Model Animal Research Institute of Nanjing University and randomly divided into 3 groups with 5 mice in each group. All animals were housed in an SPF-class animal room at a constant temperature of 23 ± 2 °C, humidity of 40 ± 10%, and a 12-hour day-night cycle, and the feed was ordinary irradiated feed (AIN-93). The above mice were intraperitoneally injected with 30 mg / kg busulfan for 5 consecutive days and freely drank distilled water to establish a reproductive injury model of busulfan in mice; then Hypocrellin A at 100 mg / kg body weight was continuously administered by intragastric gavage for 10 days. Normal group mice and busulfan model group mice were intraperitoneally injected with an equal amount of normal saline for 5 consecutive days and freely drank distilled water, and then continuously intragastrically administered an equal amount of normal saline for 10 days. After that, after 20 days of normal feeding, the mice were sacrificed by cervical dislocation. The body weight, testicular size, and testicular weight of the mice were measured, and the histological structure of the testis was detected by HE staining and the quality parameters of semen were detected by CASA.
[0037] 2.1.2 Observation of macroscopic morphology
[0038] After sacrificing the mice, the body weight of the mice was measured. Then, the abdomen of the mice was disinfected with 75% alcohol, and the testes of the mice were removed, and the surrounding adipose tissue was dissected to obtain pure bilateral mouse testes, which were photographed, weighed, and recorded. The calculation formula for the testicular mass index is: testicular mass index = testicular weight / body weight × 100%.
[0039] 2.1.3 CASA detection of semen indexes
[0040] Under anesthesia, the corpus epididymidis of the mice was removed, and the bilateral cauda epididymidis was placed in 2 mL of warm HBSS solution at 37 °C with a pH of 7.4 and incubated for 20 min, and gently shaken on a shaker to allow sperm to swim out. 100 μL of the suspension was added to 400 μL of HBSS for dilution. The diluted sperm suspension was dropped onto a glass slide, and then a computer-assisted sperm analysis (CASA) system was used to calculate sperm concentration, motility rate, and other indexes.
[0041] 2.2 Experimental Results
[0042] After the ICR mice used above were treated with intraperitoneal injection of busulfan (30 mg / kg body weight) for 5 consecutive days, reproductive damage in the mice was significantly induced. This was mainly manifested as follows: Macroscopic photographs of the bilateral testes of the mice showed that compared with normal and healthy mice, the testis volume of the busulfan-induced mice was significantly reduced. The average weight of the bilateral testes of the busulfan-induced mice was only 81.9% of the average wet weight of the bilateral testes of the normal and healthy mouse group, and the testicular mass index was significantly decreased, and the statistical t-test showed a significant difference. Compared with the model group without drug administration, the average wet weight of the bilateral testes of the Hypocrellin A treatment group of mice with a body weight of 100 mg / kg was significantly increased, even up to 94.9% of that of normal and healthy adult ICR mice ( Figure 2 A and B). CASA results showed that the semen quality of the mice in the busulfan-induced group was significantly lower than that of normal and healthy mice. Among them, the sperm concentration was only 59.3% of the average value of the normal and healthy mouse group, and the sperm motility decreased to 49.5% of the normal and healthy mouse group; while in the Hypocrellin A treatment group, the sperm concentration recovered to 90.4% of the normal and healthy mouse group, and the sperm motility increased to 81.4% of the normal and healthy mouse group ( Figure 2 C).
[0043] In summary, Hypocrellin A of the present invention can significantly improve the semen quality (such as sperm concentration and motility) of busulfan model mice, and Hypocrellin A can significantly improve the semen quality of normal mice. Therefore, Hypocrellin A can be used to prepare drugs for improving the semen quality of male mammals, and has good development value and application prospects.
[0044] The descriptions and practices disclosed in the present invention are easy to think about and understand for those of ordinary skill in the art. And without departing from the principle of the present invention, several improvements and refinements can also be made. Therefore, the modifications or improvements made without departing from the spirit of the present invention should also be regarded as within the protection scope of the present invention.
Claims
1. Application of Hypocrellin A in the preparation of drugs for improving reproductive damage in male mammals.
2. Application of Hypocrellin A in the preparation of drugs for improving semen quality of normal male mammals.
3. The use according to claims 1 and 2, characterized in that The molecular formula of Hypocrellin A is:
4. The use according to claims 1 and 2, characterized in that The drug can be administered orally, intravenously or intraarterially in various forms including solution, suspension, freeze-dried powder injection, emulsion, pill, capsule, powder, controlled release, sustained release preparation and microparticles.