CN110538191A - Application of cordycepin in preparation of preparation related to prevention and treatment of male sexual dysfunction - Google Patents
Application of cordycepin in preparation of preparation related to prevention and treatment of male sexual dysfunction Download PDFInfo
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- CN110538191A CN110538191A CN201910923546.7A CN201910923546A CN110538191A CN 110538191 A CN110538191 A CN 110538191A CN 201910923546 A CN201910923546 A CN 201910923546A CN 110538191 A CN110538191 A CN 110538191A
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- OFEZSBMBBKLLBJ-BAJZRUMYSA-N cordycepin Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)C[C@H]1O OFEZSBMBBKLLBJ-BAJZRUMYSA-N 0.000 title claims abstract description 40
- KQLDDLUWUFBQHP-UHFFFAOYSA-N Cordycepin Natural products C1=NC=2C(N)=NC=NC=2N1C1OCC(CO)C1O KQLDDLUWUFBQHP-UHFFFAOYSA-N 0.000 title claims abstract description 36
- OFEZSBMBBKLLBJ-UHFFFAOYSA-N cordycepine Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)CC1O OFEZSBMBBKLLBJ-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 206010057672 Male sexual dysfunction Diseases 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 230000001568 sexual effect Effects 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 235000020927 12-h fasting Nutrition 0.000 description 1
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- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
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- 238000002965 ELISA Methods 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 206010024419 Libido decreased Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100136062 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) PE10 gene Proteins 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
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- 239000006185 dispersion Substances 0.000 description 1
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- 238000003304 gavage Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
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- 210000004761 scalp Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L31/00—Edible extracts or preparations of fungi; Preparation or treatment thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention discloses application of cordycepin in preparation of a preparation related to male sexual dysfunction prevention and treatment, and researches show that the cordycepin has a treatment effect on male sexual dysfunction caused by diabetes, can obviously improve the times of penis erection of rats, increase the times of pounding and catching of male rats on female rats, improve the intracavernosal pressure of the rats, improve the content of serum testosterone and have a protection effect on testes of the rats. The cordycepin has obvious effect of preventing and treating male sexual dysfunction, has higher safety, is safe and effective when being applied to prepare medicines or health-care foods for preventing or treating male sexual dysfunction, and has good popularization and application prospects.
Description
Technical Field
the invention belongs to the technical field of biological medicines, and particularly relates to application of cordycepin in preparation of preparations related to male sexual dysfunction prevention and treatment.
Background
Male sexual dysfunction is mainly clinically manifested by decreased desire for sexual life, decreased frequency of erection during sexual life, decreased erection ability in different degrees, premature ejaculation, decreased sexual behavior frequency, and the like of male patients, and may be accompanied by decreased androgen and decreased gonadal function. A statistic is that 52% of men between 40 and 70 years of age suffer from different degrees of sexual dysfunction. Diseases such as overfatigue, chronic diseases, endocrine disorders, and damages of reproductive organs, or the influence of various drugs are all risk factors for inducing male sexual dysfunction. The incidence rate of the sexual dysfunction caused by diabetes is 2-5 times of that of non-diabetic patients, and the incidence age of the diabetes is 10 years earlier than that of the non-diabetic patients. The clinical prevention and treatment of male sexual dysfunction mainly comprises drug intervention and psychological dispersion, and has many adverse drug reactions and unsatisfactory long-term curative effect, which seriously affects the life quality of patients. Therefore, the search for effective drugs or health foods for preventing or treating male sexual dysfunction has been a hot spot of research and attention in andrology.
Since Cordycepin was discovered and isolated as a pure product by Cunningham, a German scientist in the middle of the 20 th century, it was discovered that the specific structure of Cordycepin adenosine determines its biological activity. It can promote cell differentiation, enhance the antitumor activity of some cell lines and the chemotaxis of macrophage system, and has the functions of resisting bacteria, preventing cancer, resisting tumor, resisting senility, regulating immunity, etc. In recent years, the development and application of cordycepin are widely concerned in the field of natural products at home and abroad, but no relevant research and report on the prevention and treatment of male sexual dysfunction is found at present.
Disclosure of Invention
the invention aims to solve the technical problem of providing a new application method of cordycepin aiming at the defects of the prior art.
Specifically, the invention discloses an application of cordycepin in preparation of a preparation related to prevention and treatment of male sexual dysfunction.
Furthermore, the male sexual dysfunction is male sexual dysfunction caused by diabetes, and comprises one or more symptoms of hyposexuality, erectile dysfunction, premature ejaculation, or accompanied male hormone decline, hypogonadism and the like.
Wherein the related preparation comprises a medicament, a health product or a food.
Further, the medicine is a pharmaceutical composition containing cordycepin and a pharmaceutically acceptable carrier.
Wherein, the dosage form of the pharmaceutical composition is oral preparation, injection or external preparation.
Has the advantages that:
The research of the invention finds that the cordycepin has a treatment effect on male sexual dysfunction caused by diabetes, can obviously improve the times of penis erection of rats, increase the times of capturing male rats on female rats, improve the intracavernosal pressure of the penis of the rats, improve the content of serum testosterone and have a protection effect on the testis of the rats. The application is different from the applications of the cordycepin reported in the past, a new application field is developed for the cordycepin, and a new idea is provided for the further development and utilization of the cordycepin.
The cordycepin has obvious effect of preventing and treating male sexual dysfunction, has higher safety, is safe and effective when being applied to prepare medicines or health-care foods for preventing or treating male sexual dysfunction, and has good popularization and application prospects.
Drawings
The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.
FIG. 1 shows the effect of cordycepin on the anti-fatigue ability of rats; wherein a represents comparison to the normal group and b represents comparison to the model group; *: p is less than 0.05; **: p is less than 0.01.
FIG. 2 is a graph showing the effect of cordycepin on intracavernosal pressure (ICP) in male rats; wherein, (a) a normal group, (b) a model group, (c) a sildenafil group, (d) a cordycepin group, and (f) a ratio of intracavernosal pressure to mean arterial pressure; a represents comparison with normal group, b represents comparison with model group; *: p is less than 0.05; **: p is less than 0.01.
FIG. 3 is the effect of cordycepin on the index of testis and accessory gonads of male rats; wherein a represents comparison to the normal group and b represents comparison to the model group; *: p is less than 0.05; **: p is less than 0.01.
FIG. 4 is a graph of the effect of cordycepin on testosterone in male rats; wherein a represents comparison to the normal group and b represents comparison to the model group; *: p is less than 0.05; **: p is less than 0.01.
Detailed Description
The invention will be better understood from the following examples.
Example 1 establishment of a rat model of diabetic dysfunction and group administration
This example is a specific example of modeling, i.e. using a manual intervention, a pathological model of sexual dysfunction was made from normal rats.
The experimental method comprises the following steps: 40 male SD rats were acclimatized for 3 days. After fasting for 12h, 10 of the normal control groups were randomly selected and used as controls by intraperitoneal injection of citric acid-sodium citrate buffer. The remaining animals were injected intraperitoneally with streptozotocin (solvent citric acid buffer, pH 4.5) in a single dose of 65 mg/kg. Blood glucose above 16.7mM after 7 days suggests the development of a diabetic model. If the blood glucose is below 16.7mM, the same dose of streptozotocin is injected intraperitoneally again.
Rats with persistent hyperglycemia for 8 weeks developed a sexual dysfunction model, which was divided into three groups: model control group (given physiological saline), sildenafil positive control group (10mg/kg per day), and cordycepin group (20mg/kg per day). The gavage was continued for 4 weeks.
Example 2 Effect of Cordycepin on sexual behavior in Male rats
The experimental method comprises the following steps: several cages were taken, 1 male rat from example 1 was placed in each cage, and allowed to acclimate for 5min under dark light. Then 1 female rat was placed and recording was started: the time from the time when the female mouse is thrown to the time when the male mouse catches the female mouse for the 1 st time is the catching latent period; the number of times that the male mouse caught the female mouse within 20min from the female mouse.
And (3) calculating results and carrying out statistical analysis: data of each experimental group are expressed by mean ± standard deviation (mean ± sd), homogeneity of variance test is performed by using system statistics software SPSS 17.0, one-way ANOVA (one-way ANOVA) is used for each group with homogeneous variance, and LSD method is used for comparison among groups. The difference is statistically significant when P is less than 0.05. See table 1 for specific experimental results.
TABLE 1 Effect of Cordycepin on rat sexual behavior
Note: a represents comparison with normal group, b represents comparison with model group; *: p is less than 0.05; **: p is less than 0.01
The results show that the latency of catching is greatly increased (P <0.01) and the catching times are remarkably reduced (P <0.01) compared with the normal group in the diabetic dysfunction model group, which indicates that the pathological model is successful. Compared with the model control group, the sildenafil and cordycepin groups have obvious improvement on the capture latency and capture times (P is less than 0.01).
Example 3 Effect of Cordycepin on anti-fatigue ability of Male rats
The experimental method comprises the following steps: the tail root of each group of experimental rats in example 1 was loaded with 5% weight lead skin and placed in a swimming box for swimming. The water depth is not less than 60cm, the water temperature is 25 +/-1 ℃, and the time from swimming to exhaustion of the rat, namely the weight-bearing swimming time of the rat, is recorded.
And (3) calculating results and carrying out statistical analysis: data of each experimental group are expressed by mean ± standard deviation (mean ± sd), homogeneity of variance test is performed by using system statistics software SPSS 17.0, one-way ANOVA (one-way ANOVA) is used for each group with homogeneous variance, and LSD method is used for comparison among groups. The difference is statistically significant when P is less than 0.05. See fig. 1 for specific experimental results.
The result shows that the weight-bearing swimming time of the rats in the diabetic dysfunction model group is extremely remarkably reduced (P <0.01) compared with that of the normal group, which indicates that the fatigue resistance of the rats in the diabetic dysfunction model group is remarkably reduced; compared with the model group, sildenafil and cordycepin both remarkably increase the weight-bearing swimming time of rats (P <0.05), which indicates that sildenafil and cordycepin both can better improve the anti-fatigue capability of rats.
Example 4 Effect of Cordycepin on intracavernosal pressure (ICP) of Male rat penis
Experimental apparatus: a signal acquisition processor (Yimei, MedLab-U/4C 501H); 40kPa pressure transducer (YP100 type, Kyoto Xinghangxing Korea Co., Ltd.)
The experimental method comprises the following steps:
(1) Rats were anesthetized by intraperitoneal injection of sodium pentobarbital. In the supine position, the limbs are fixed and the hair around the surgical field is cut off.
(2) After the anesthesia is successful, the dorsal position is fixed, the incision in the middle of the abdomen is made into the abdomen, the prostate is found, the back of the two side lobes of the prostate is carefully dissociated, and the stellate ganglion of the pelvic cavity can be exposed.
(3) Careful separation of the two major input branches, the pelvic and hypogastric nerves, and the cavernous nerve, the largest output branch running laterally along the urethra, were identified by the pelvic stellate ganglion. A bipolar electrode is placed 1-2 mm away from the pelvic stellate ganglion on a cavernous nerve, the positive electrode is located at the proximal end of the nerve, the distance between the two electrodes is 1mm, and the diameter of the electrode is about 0.2 mm.
(4) Cutting penis foreskin, peeling off, fully exposing penis cavernous body, puncturing scalp needle in cavernous body at one side
(5) The device is connected with a signal acquisition processor through a catheter, heparin solution (250U/ml) is filled in the catheter, and air bubbles in the catheter are emptied.
(6) Electrical stimulation is carried out on cavernous nerves, and a signal acquisition processor is adjusted to enable stimulation parameters to be continuous square wave stimulation, wave width of 5ms, frequency of 15Hz and voltage of 7.5V, wherein each stimulation lasts for 60 s.
(7) The change in ICP over the course of the electrical stimulation was recorded.
(8) Mean Arterial Pressure (MAP) determination: the median incision of the neck is made, the left common carotid artery is exposed and incised and placed in a PE10 tube, the pressure transducer is connected with the rear part of the left common carotid artery through a PE50 tube, and the mean arterial pressure of the rat is continuously monitored by a direct method
And (3) calculating results and carrying out statistical analysis: data of each experimental group are expressed by mean ± standard deviation (mean ± sd), homogeneity of variance test is performed by using system statistics software SPSS 17.0, one-way ANOVA (one-way ANOVA) is used for each group with homogeneous variance, and LSD method is used for comparison among groups. The difference is statistically significant when P is less than 0.05. See fig. 2 for specific experimental results.
The result shows that the cordycepin has good effect of improving the erectile function of rats in a diabetes model group (P is less than 0.01). The ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was significantly reduced (P <0.01) in the diabetic dysfunctional rats compared to the normal rats, indicating that the erectile function was severely impaired in the model rats. The sildenafil and cordycepin treated rats have very remarkable improvement (P is less than 0.01) compared with model rats, namely the sildenafil and cordycepin treated rats can effectively improve the erection function of the rats.
Example 5 Effect of Cordycepin on the index of testis and accessory gonads in Male rats
The experimental method comprises the following steps: each group of rats was weighed and sacrificed, and the testes, epididymis, seminal vesicle glands, and glandulae preputiales were removed, precisely weighed, and organ index calculated: [ organ index (%) ═ organ weight (g)/body weight (g) × 100% ]
And (3) calculating results and carrying out statistical analysis: data of each experimental group are expressed by mean ± standard deviation (mean ± sd), homogeneity of variance test is performed by using system statistics software SPSS 17.0, one-way ANOVA (one-way ANOVA) is used for each group with homogeneous variance, and LSD method is used for comparison among groups. The difference is statistically significant when P is less than 0.05. See fig. 3 for specific experimental results.
The results show that the indexes of testis, epididymis and seminal vesicle viscera in the diabetic dysfunction model group are all reduced compared with the normal group, the indexes of testis and seminal vesicle are both obviously improved after the treatment of cordycepin (P <0.05), and the epididymis has no obvious influence (P > 0.05). And the glandular preputiales between groups were not significant (P > 0.05).
Example 6 Effect of Cordycepin on serum testosterone in Male rats
The experimental method comprises the following steps: the method comprises the steps of taking rat serum, and detecting the content of male hormone testosterone in the rat serum of each group by using an enzyme-linked immunosorbent assay according to the kit specification.
And (3) calculating results and carrying out statistical analysis: data of each experimental group are expressed by mean ± standard deviation (mean ± sd), homogeneity of variance test is performed by using system statistics software SPSS 17.0, one-way ANOVA (one-way ANOVA) is used for each group with homogeneous variance, and LSD method is used for comparison among groups. The difference is statistically significant when P is less than 0.05. See fig. 4 for specific experimental results.
The results show that the serum testosterone (T) level of the rats with diabetic dysfunction is extremely reduced compared with that of the rats with normal diabetes dysfunction (P < 0.01). Through drug treatment, compared with a pathological model group, the serum testosterone of the sildenafil group and the cordycepin group is obviously improved (P is less than 0.05).
The invention provides a thought and a method for application of cordycepin in preparation of preparations related to male sexual dysfunction, and particularly provides a plurality of methods and ways for realizing the technical scheme, the above description is only a preferred embodiment of the invention, and it should be noted that for persons skilled in the art, a plurality of improvements and decorations can be made without departing from the principle of the invention, and the improvements and decorations are also regarded as the protection scope of the invention. All the components not specified in the present embodiment can be realized by the prior art.
Claims (6)
1. Application of cordycepin in preparing preparation for preventing and treating male sexual dysfunction is provided.
2. The use according to claim 1, wherein the male sexual dysfunction is male sexual dysfunction caused by diabetes.
3. The use according to claim 2, wherein the male sexual dysfunction caused by diabetes mellitus comprises decreased libido, erectile dysfunction, premature ejaculation or one or more symptoms accompanied by decreased androgens and decreased gonadal function.
4. Use according to claim 1 or 2, wherein the related preparation comprises a medicament, a nutraceutical or a food product.
5. The use according to claim 4, wherein the medicament is a pharmaceutical composition comprising cordycepin and a pharmaceutically acceptable carrier.
6. The use of claim 5, wherein the pharmaceutical composition is in the form of an oral preparation, an injection or an external preparation.
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