CN115040481A - Application of oleanolic acid liposome in preparation of medicine for improving cisplatin-induced spermatogenesis dysfunction - Google Patents
Application of oleanolic acid liposome in preparation of medicine for improving cisplatin-induced spermatogenesis dysfunction Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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Abstract
An application of oleanolic acid liposome in preparing a medicine for improving spermatogenic disorder caused by cisplatin relates to the field of research and development of spermatogenic disorder medicines. The functions of the oleanolic acid liposome comprise that the sperm density and the sperm motility of a mouse model with spermatogenic disorder caused by cisplatin are obviously improved; the curve speed, the linear speed and the average speed of epididymal tail sperms of a mouse model with spermatogenic disorder caused by cisplatin are obviously improved; the sperm teratogenesis rate of a mouse model with spermatogenesis dysfunction caused by cisplatin is obviously improved; the testosterone level in the serum of the mouse model with spermatogenesis dysfunction caused by the cisplatin is obviously improved. The sperm density, the sperm motility, the average path speed and the linear movement speed of the sperm and the testosterone level of the mice of each dose group of the oleanolic acid liposome prepared by the invention are obviously higher than those of the model group, and the sperm aberration rate is obviously lower than that of the model group; the oleanolic acid liposome can improve the spermatogenic disorder of the cisplatin-induced spermatogenic disorder mouse model and obviously improve the reproductive capacity of the cisplatin-induced spermatogenic disorder mouse model.
Description
Technical Field
The invention relates to the technical field of research and development of spermatogenic disorder medicines, and particularly relates to application of oleanolic acid liposome in preparation of medicines for improving spermatogenic disorder caused by cisplatin.
Background
The proportion of male sterility In infertile couples is about 30-40%, there are many causes of male sterility, and spermatogenesis disorders (oligospermia, asthenospermia and azoospermia) are all the main causes of male sterility and reduced fertility (CHU F H, ZHANG W X, GUO W B, ethyl, Oleanolic Acid-amino acids differences: Design, Synthesis, and Hepatoprotective Evaluation In and In Vivo [ J ]. Molecules,2018,23(2):322.DOI:10.3390/Molecules 20322.). Improving spermatogenic disorder is of great significance in treating male infertility.
Cisplatin (DDP) is the first cycle non-specific antineoplastic drug to be used in tumor therapy, and has therapeutic effects on lung cancer, prostate cancer, lymph cancer and the like (NAASSE Y, CHARUTE H, EI H OUATEB, ethyl, chromosomal antibodies and Y chromosome microorganisms in interferon men from Morocco [ J ]. BMC Urol,2015,15:95.DOI:10.1186/s 12894-015-. The compound has damage effect on male reproductive system in clinical application, has potential malformation risk on offspring, can be used as an inducer of a spermatogenic disorder model, and is an ideal medicament for preparing the spermatogenic disorder (KANG SH, LEE HJ, JEONG SJ, et al.protective effect of Bojungdackstang on soluble-induced cytotoxicity and apoptosis in MCF-10A Breast endothiral cells, environ toxicity Pharmacol,2009,28(3):430-438.DOI:10.1016/j. etap.2009.07.007.). It is currently believed that the mechanism of cisplatin-induced dysspermia may be the generation of excessive toxic electrophilic substances, leading to decreased free radical scavenging enzyme activity, resulting in free radical accumulation, lipid peroxidation, destruction of cell membrane structures, germ cell damage, and thus a change in the sperm microenvironment (KILARKA JE N, MOUSA AM, Al-BADER MM, et Al, antibiotic engineering of the receptor of the same cycle of nucleic acids, etoposide, and platelet-induced transcriptional function, tissue-transcriptional activity, and fertility in rates [ J ] Fertil Steril,2013,100(4):1151-1159.DOI: 10.1016/j.ferr.2013.06.019.).
Oleanolic Acid (OA), also known as indigenous acid, is a pentacyclic triterpenoid compound, is a natural phytochemical component, widely exists in the plant world in a free or combined glycoside form, has wide pharmacological action, and is mainly used for treating acute icteric hepatitis and chronic viral hepatitis. The existing research shows that the oleanolic acid has poor water solubility and low bioavailability. The oleanolic acid liposome is prepared from oleanolic acid.
Until now, no report has been made on the research of oleanolic acid and oleanolic acid liposome in improving cisplatin-induced spermatogenic disorder.
Disclosure of Invention
The invention aims to provide application of oleanolic acid liposome in preparation of a medicine for improving spermatogenesis dysfunction caused by cisplatin.
The technical scheme adopted by the invention for solving the technical problem is as follows:
the oleanolic acid liposome is applied to preparation of the medicine for improving spermatogenesis dysfunction caused by cisplatin.
In a preferred embodiment, the dosage of the oleanolic acid liposome is 25-100 mg/kg.
In a preferred embodiment, the oleanolic acid liposome is used at a dose of 100 mg/kg.
As a preferred embodiment, the functions of the oleanolic acid liposome include:
(1) the sperm density and the sperm motility of a mouse model with spermatogenic disorder caused by the cisplatin are obviously improved;
(2) the curve speed, the linear speed and the average speed of epididymal tail sperms of a mouse model with spermatogenic disorder caused by cisplatin are obviously improved;
(3) the sperm teratogenesis rate of a mouse model with spermatogenesis dysfunction caused by cisplatin is obviously improved;
(4) the testosterone level in the serum of the mouse model with spermatogenesis dysfunction caused by the cisplatin is obviously improved.
As a preferred embodiment, the preparation method of the oleanolic acid liposome comprises the following steps:
(1) weighing oleanolic acid, soybean lecithin and cholesterol according to the mass ratio of oleanolic acid to soybean lecithin to cholesterol of 3:18:2, adding absolute ethyl alcohol, and placing on a magnetic stirrer to be fully mixed and dissolved to obtain a lipoid solution;
(2) dissolving Tween-80 in PBS, and heating at 37-49 ℃ to obtain an aqueous phase solution;
(3) slowly injecting the lipoid solution into the water phase solution by using an injector, stirring by using a magnetic stirrer while injecting, and after the lipoid solution and the water phase solution are fully and uniformly mixed, carrying out rotary evaporation on the obtained solution to completely volatilize ethanol to obtain milky white suspension;
(4) ultrasonically dispersing the milky white suspension into an emulsion suspension, filtering, and freeze-drying to obtain the oleanolic acid liposome.
As a preferred embodiment, in step (2), 20. mu.L of Tween-80 was dissolved in 10mL of PBS and heated at 43 ℃ to obtain an aqueous solution.
In a preferred embodiment, in step (3), the solution obtained is subjected to rotary evaporation at 45 ℃ at 15 r/min.
In a preferred embodiment, in the step (4), the milky white suspension is subjected to ultrasonic dispersion at 45 ℃ and 100Hz to obtain an emulsion suspension, and the emulsion suspension is filtered by a 0.45-micron filter membrane and then is subjected to freeze drying to obtain the oleanolic acid liposome.
As a preferred embodiment, the prepared oleanolic acid liposome has an average particle size of (253.39 + -10.89) nm and an encapsulation efficiency of (96.34 + -2.31)%.
The invention has the beneficial effects that:
the invention researches the protection effect of oleanolic acid liposomes (OA-Lips) on mouse spermatogenesis disorder caused by cisplatin through experiments. Experiments prove that the sperm density, the sperm motility, the average path speed, the linear motion speed and the testosterone level of mice in each dose group of the oleanolic acid liposomes (OA-Lips) prepared by the invention are obviously higher than those of a model group, and the sperm aberration rate is obviously lower than that of the model group (p < 0.05). The oleanolic acid liposomes (OA-Lips) can improve the spermatogenesis dysfunction of cisplatin-induced spermatogenesis dysfunction mouse models, and obviously improve the reproductive capacity of cisplatin-induced spermatogenesis dysfunction mouse models.
The oleanolic acid liposome (OA-Lips) prepared by the preparation method has the advantages of average particle size of (253.39 +/-10.89) nm, encapsulation efficiency of (96.34 +/-2.31)%, round appearance, uniform size and good water solubility.
Drawings
FIG. 1 is a smear showing the effect of oleanolic acid liposomes (OA-Lips) on the semen quality of each group of mice.
FIG. 2 shows the effect of Oleanolic acid liposomes (OA-Lips) on sperm teratogenesis in mice of each group (. times.400). In the figure, A is normal sperm; b is bipitch sperm; c is fat head sperm; d is unhooked sperm; e is banana type sperm; f is tail fold sperm.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
First, experimental animal
The body mass of the SPF-grade adult male ICR mice is 18-22 g (Changchun hundred million laboratory animal technology Co., Ltd., license number: SCXK (Ji) 20180007). Mice were bred adaptively for 5d before the experiment. Feeding conditions are as follows: the temperature is 18-22 ℃, the humidity is 45% -65%, the light and shade alternate for 12h, and the drinking water can be freely taken.
Second, experiment reagent
Oleanolic acid was purchased from sienna bio-technology; soybean lecithin was purchased from phospholipid technology, Inc., of Mei Asias, Beijing; cholesterol was purchased from Tianjin chemical reagent works; cisplatin for injection was purchased from zilu pharmaceutical co ltd; testosterone ELISA kits were purchased from Beijing Bootoudoda technologies, Inc.
Third, the experimental apparatus
SynergyH1M microplate reader (BioTek, USA), EV311 rotary evaporator (Beijing Leibertai), Freezone2.5 freeze drier (Labconco, USA), SCA-H-01P semen analysis automatic detection system (SCA, Spain); zeta particle size analyzer (british marvin); 1260Infinity high performance liquid chromatograph (agilent, usa).
EXAMPLE 1 preparation of Oleanolic acid liposomes (OA-Lips)
Preparing oleanolic acid liposome (OA-Lips) by adopting an ethanol injection method, accurately weighing 300mg of oleanolic acid, 1800mg of soybean lecithin and 200mg of cholesterol, placing the mixture in a beaker, adding 10mL of absolute ethanol, and placing the beaker on a magnetic stirrer to be fully mixed and dissolved to obtain a lipoid solution; dissolving 20 mu L of Tween-80 in 10mL of PBS, and heating at 43 ℃ to obtain an aqueous phase solution; slowly injecting the lipoid solution into the water phase solution by using a 5mL injector, and stirring by using a magnetic stirrer while injecting; after the lipoid solution and the aqueous phase solution are fully mixed, putting the obtained solution into a round-bottom flask, and performing rotary evaporation on a rotary evaporator (EV311) at the temperature of 45 ℃ at 15r/min to completely volatilize ethanol to obtain milky OA-Lips suspension; and (3) placing the milky white OA-Lips suspension into an ultrasonic cleaner, performing ultrasonic dispersion on the milky white OA-Lips suspension at the temperature of 45 ℃ at 100Hz to obtain an emulsion suspension, filtering the obtained emulsion suspension by using a 0.45 mu m filter membrane, and performing freeze drying to obtain the oleanolic acid liposomes (OA-Lips).
The average particle diameter of the oleanolic acid liposome (OA-Lips) prepared by the experiment is (253.39 +/-10.89) nm, the encapsulation efficiency is (96.34 +/-2.31)%, the appearance is circular, the size is uniform, and the water solubility is good.
Example 2 protective Effect of Oleanolic acid liposomes (OA-Lips) on cisplatin-induced spermatogenic dysfunction in mice
1. Animal grouping and administration
60 SPF-grade adult male ICR mice were randomly divided into a control group, a model group, a positive control group, an OA-Lips low dose group, an OA-Lips medium dose group and an OA-Lips high dose group, and 10 mice were each group. The OA-Lips low-dose group, the OA-Lips medium-dose group and the OA-Lips high-dose group are respectively administrated with 25mg/kg, 50mg/kg and 100mg/kg oleanolic acid liposome (OA-Lips) intragastric administration every day, and the positive control group is administrated with 50mg/kg vitamin E aqueous solution intragastric administration every day. And continuously intragastrically irrigating the OA-Lips low-dose group, the OA-Lips medium-dose group, the OA-Lips high-dose group and the positive control group for 28 d. 28d, mice in each group except the control group were given a single intraperitoneal injection of 10mg/kg cisplatin solution, and the control group was given the same dose of saline.
2. Determination of sperm density, sperm motility rate and deformity rate of mice
2.1 test procedure
After 3 days of administration, the eyeballs draw blood to kill the mice, the abdominal wall is cut open, the reproductive system is exposed, epididymis on both sides is picked up, the mice are cleaned in a preheated physiological saline surface dish in a 37 ℃ incubator, the mice are quickly placed in 1mL of physiological saline incubated at 37 ℃, the epididymis tail is slightly cut open, the mice are placed in the 37 ℃ incubator for incubation for 10min, after the sperms are fully dissociated, the sperms are filtered to a new EP test tube through four layers of lens wiping paper, 10 mu L of the sperms are taken out and added into a sperm counting plate, the observation and the photographing are carried out under a light mirror, the head-recording and tail-recording principles are followed, and the sperm density and vitality parameters are automatically counted by SCA software.
Taking another 5 mu L of smear from the residual sperm suspension, drying in air, fixing with methanol, staining with 1% eosin water solution for 15min, washing with running water, drying in air, examining sperm morphology under a high power microscope, examining 200-500 intact sperms per mouse, and examining at least 1000 sperms per group. The teratospermia is mainly manifested in the head of the sperm and can be classified into the following types according to the forms: unhooked, banana-shaped, amorphous, double-ended, tail-folded, fat-headed, and the like. Sperm aberration (%). rate is the number of teratospermia/total number of counted sperm (1000) × 100.
The SPSS16.0 software is used for data processing, and all data are subjected to mean plus or minus standard deviation
Mean comparisons between groups were performed by One-way anova (One-way anova), and pairwise comparisons between groups were performed by Least Significant Difference (LSD) test, with a test level α of 0.05.
2.2 test results
2.2.1 smear observation OA-Lips on the quality of the semen of each group of mice, the result is shown in figure 1, the observation of microscope after the semen smear shows that the proportion of the moving sperm of the mice of the model group and the density of the sperm are obviously reduced compared with the control group; the proportion of motile sperm and the density of sperm were significantly increased in the positive control group and the OA-Lips high dose group.
2.2.2 the effect of OA-Lips on sperm motility parameters of various groups of mice is shown in Table 1. As can be seen from the results in Table 1, the number of the sperm which moved forward and did not move forward in each group of mice gradually increased and the number of the sperm which did not move forward gradually decreased with the increase of the dosage of OA-Lips. The number of the forward movement sperms and the non-forward movement sperms of the model group mouse is significantly lower than that of the control group, and the number of the inactive sperms is significantly higher than that of the control group (p < 0.05); the number of sperms capable of generating forward motion of mice in the OA-Lips middle-dose group and the OA-Lips high-dose group is remarkably higher than that of the mice in the model group (p < 0.05); the proportion of non-forward movement sperms of the mice in the OA-Lips high-dose group is obviously higher than that of the mice in the model group, the OA-Lips low-dose group and the OA-Lips medium-dose group (p is less than 0.05); the proportion of non-motile sperm in the model group is significantly higher than that in the control group (p < 0.05); the number of non-motile sperm was significantly lower in the OA-Lips high dose group mice than in the model group and OA-Lips low dose group (p < 0.05); the total sperm activity of the model group is significantly lower than that of the control group (p < 0.05); the total sperm motility rates of the OA-Lips low-dose group, the OA-Lips medium-dose group and the OA-Lips high-dose group are higher than those of the model group, but the comparison difference is not significant (p is more than 0.05).
TABLE 1 influence of OA-Lips on sperm motility parameters of groups of mice
Note: p compared to control group<0.05; in comparison with the set of models, # p<0.05; compared with the group with low dosage of OA-Lips, $ p<0.05; compared with the dosage group in OA-Lips, ▽ p<0.05；n＝10。
in conclusion, the oleanolic acid liposomes (OA-Lips) prepared in example 1 intervene in mouse spermatogenesis dysfunction caused by cisplatin, and the results show that the sperm density and sperm motility of mice in the low, medium and high dosage groups of OA-Lips are remarkably increased, which indicates that the oleanolic acid liposomes (OA-Lips) can remarkably improve the sperm density and sperm motility of the mice, thereby improving the mouse spermatogenesis dysfunction caused by cisplatin.
2.2.3 the effect of OA-Lips on sperm motility parameters of each group of mice is shown in Table 2. from the results of Table 2, as the dosage of OA-Lips is increased, the sperm cells of each group of mice gradually increase in VCL (curve velocity), VSL (linear velocity), VAP (mean velocity), LIN (linear index), STR (linear index), WOB (vibration index), ALH (mean amplitude of lateral head movement), and BCF (whipping frequency). The model mice had significantly reduced sperm VCL (curve velocity), VSL (linear velocity) and WOB (vibration index) compared to the control group (p < 0.05); compared with the model group, the WOB (vibration index) of the sperm of the mice in the positive control group is remarkably increased (p <0.05), the VCL of the sperm of the mice in the OA-Lips medium dosage group and the OA-Lips high dosage group is remarkably increased (p <0.05), and the VSL (linear velocity), LIN (linear index), STR (linear index), WOB (vibration index) and ALH (average amplitude of lateral movement of the head) of the sperm of the mice in the OA-Lips high dosage group are remarkably increased (p < 0.05); the VSL (linear velocity) and WOB (vibration index) of the OA-Lips high dose group mouse sperm were significantly higher than those of the low and medium dose groups (p < 0.05); STR (linear index) of mouse sperms in OA-Lips high dose group is significantly higher than that in positive control group (p < 0.05).
TABLE 2 influence of OA-Lips on the kinematic parameters of the groups of mice
Note: p compared to control group<0.05; in comparison with the set of models, # p<0.05; compared with the positive control group, the test results show that, ▼ p<0.05; compared with the group with low dosage of OA-Lips, $ p<0.05; compared with the dosage group in OA-Lips, ▽ p<0.05；n＝10。
in conclusion, in terms of the main indexes of the kinematic measurement parameters reflecting the sperm motility, VCL (curve speed), VSL (linear speed) and VAP (average speed) of each dosage group of OA-Lips are obviously improved, and the surface of the oleanolic acid liposomes (OA-Lips) can improve the sperm motility of mice by improving the average movement speed, the linear movement speed and the curve movement speed of epididymal tail sperm.
2.2.4 the influence of OA-Lips on the sperm aberration rate of each group of mice is shown in Table 3, and the results in Table 3 show that the sperm aberration rate of the model group of mice is obviously higher than that of the control group (p < 0.05); the sperm aberration rate of mice in the OA-Lips high-dose group is obviously lower than that of the model group, the positive control group and the OA-Lips low-dose group (p is less than 0.05); the sperm teratogenesis rate of mice in the positive control group and the OA-Lips dosage group is obviously lower than that of the model group (p < 0.05). As can be seen from FIG. 2, the double-headed, fat-headed, hitless, banana-shaped and tail-folded teratospermia were observed in the model group. After OA-Lips administration, the sperm teratogenesis rate of the mice is obviously improved.
TABLE 3 influence of OA-Lips on sperm teratogenesis in mice of each group
| Grouping | Sperm abnormality rate (%) |
| Control group | 6.78±0.97 |
| Model set | 13.20±1.81 * |
| Positive control group | 9.97±1.68 *# |
| OA-Lips Low dose group | 11.15±2.80 * |
| OA-Lips medium dose group | 8.86±2.16 # |
| OA-Lips high dose group | 7.28±1.35 #▼$ |
Note: p compared to control group<0.05; in comparison with the set of models, # p<0.05; compared with the positive control group, the test results show that, ▼ p<0.05; compared with the group with low dosage of OA-Lips, $ p<0.05; compared with the dosage group in OA-Lips, ▽ p<0.05；n＝10。
in conclusion, in the aspect of sperm malformation detection, the sperm malformation rate of mice in each dosage group of OA-Lips is obviously reduced, and the reproductive capacity of the mice is improved.
3. Mouse serum reproductive hormone assay
3.1 test procedure
Centrifuging whole blood of the mouse at 3000rpm for 10min, taking supernatant, measuring the testosterone level in the serum of the mouse by using an enzyme linked immunosorbent assay kit, and finishing the experimental steps according to the specification of the enzyme linked immunosorbent assay kit. The SPSS16.0 software is used for data processing, and all data are subjected to mean plus or minus standard deviation
Mean comparisons between groups were performed by One-way anova (One-way anova), and pairwise comparisons between groups were performed by Least Significant Difference (LSD) test, with a test level α of 0.05.
3.2 test results
The influence of OA-Lips on the testosterone level in the serum of each group of mice is shown in Table 4, and the results in Table 4 show that the testosterone level in the serum of the model group of mice is obviously lower than that of the control group (p is less than 0.05); the testosterone level in the serum of mice in a positive control group, an OA-Lips low-dose group, an OA-Lips medium-dose group and an OA-Lips high-dose group is obviously higher than that of mice in a model group (p < 0.05); the testosterone levels in serum of mice in the OA-Lips medium-dose group and the OA-Lips high-dose group were significantly higher than those in the OA-Lips low-dose group (p < 0.05).
TABLE 4 Effect of OA-Lips on serum testosterone levels in mice of various groups
| Grouping | Testosterone (nmol/L) |
| Control group | 6.24±0.10 |
| Model set | 4.78±0.07 * |
| Positive control group | 5.46±0.13 *# |
| OA-Lips Low dose group | 5.67±0.08 *# |
| OA-Lips medium dose group | 6.06±0.01 #▼$ |
| OA-Lips high dose group | 6.23±0.01 #▼$ |
Note: p compared to control group<0.05; in comparison with the set of models, # p<0.05; compared with the positive control group, the test results show that, ▼ p<0.05; compared with the group with low dosage of OA-Lips, $ p<0.05；n＝10。
testosterone is an important component constituting androgen, and in male individuals, testosterone is synthesized and secreted mainly by leydig cells. Part of testosterone secreted by the testicular interstitial cells enters blood circulation to maintain the secondary androgenic characteristics; one part acts on testicular spermatogenic epithelial cells and participates in spermatogenesis and maturation. Testosterone cannot be lost in the development and maturation process of the male individual reproductive system, normal development of sperms can be maintained by physiological dose of testosterone, and abnormal development of sperms can be caused by reduction of testosterone level or synthesis disorder. In the experiment, after the administration of OA-Lips, the testosterone level in the serum of mice in the group with low and medium dosage of OA-Lips is obviously improved, which shows that OA-Lips improves the reduction of the testosterone level in the serum of the mice, thereby improving the sperm quality and the vitality of the mice and further improving the reproductive capacity of the mice.
The invention discloses application of oleanolic acid liposome in preparation of a medicine for improving spermatogenesis dysfunction caused by cisplatin, and a person skilled in the art can use the contents for reference and appropriately improve process parameters for realization. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the invention has been described in terms of preferred embodiments, it will be apparent to those skilled in the art that the technology can be practiced and applied by modifying or appropriately combining the products described herein without departing from the spirit and scope of the invention.
Claims (9)
1. Application of oleanolic acid liposome in preparing medicine for improving cisplatin-induced spermatogenic disorder is provided.
2. The use according to claim 1, wherein the oleanolic acid liposome is used in an amount of 25-100 mg/kg.
3. The use of claim 2, wherein said oleanolic acid liposomes are used at a dose of 100 mg/kg.
4. The use according to claim 1, wherein the functions of the oleanolic acid liposome comprise:
(1) the sperm density and the sperm motility of a mouse model with spermatogenic disorder caused by the cisplatin are obviously improved;
(2) the curve speed, the linear speed and the average speed of epididymal tail sperms of a mouse model with spermatogenic disorder caused by cisplatin are obviously improved;
(3) the sperm teratogenesis rate of a mouse model with spermatogenesis dysfunction caused by cisplatin is obviously improved;
(4) the testosterone level in the serum of the mouse model with spermatogenesis dysfunction caused by the cisplatin is obviously improved.
5. The use of claim 1, wherein the preparation method of the oleanolic acid liposome comprises the following steps:
(1) weighing oleanolic acid, soybean lecithin and cholesterol according to the mass ratio of the oleanolic acid to the soybean lecithin to the cholesterol of 3:18:2, adding absolute ethyl alcohol, and placing on a magnetic stirrer to be fully mixed and dissolved to obtain a lipoid solution;
(2) dissolving Tween-80 in PBS, and heating at 37-49 ℃ to obtain an aqueous phase solution;
(3) slowly injecting the lipoid solution into the water phase solution by using an injector, stirring by using a magnetic stirrer while injecting, and after the lipoid solution and the water phase solution are fully and uniformly mixed, carrying out rotary evaporation on the obtained solution to completely volatilize ethanol to obtain milky white suspension;
(4) ultrasonically dispersing the milky white suspension into an emulsion suspension, filtering, and freeze-drying to obtain the oleanolic acid liposome.
6. The use of claim 5, wherein in step (2), 20. mu.L of Tween-80 is dissolved in 10mL of PBS and heated at 43 ℃ to obtain an aqueous solution.
7. The use according to claim 5, wherein in step (3), the solution obtained is subjected to rotary evaporation at 45 ℃ at 15 r/min.
8. The use as claimed in claim 5, wherein in step (4), the opalescent suspension is ultrasonically dispersed to an emulsion suspension at 45 ℃ under 100Hz, and then is filtered by a 0.45 μm filter membrane and freeze-dried to obtain the oleanolic acid liposome.
9. The use according to claim 5, wherein the prepared oleanolic acid liposome has an average particle size of (253.39 ± 10.89) nm and an encapsulation efficiency of (96.34 ± 2.31)%.
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| CN113398078A (en) * | 2021-08-03 | 2021-09-17 | 山西黄河中药有限公司 | Granular traditional Chinese medicine for improving ovarian reserve function and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1923178A (en) * | 2006-08-22 | 2007-03-07 | 河南大学 | Oleanolic acid liposome preparation, freeze dried powder injecta thereof and its preparation |
| CN113398078A (en) * | 2021-08-03 | 2021-09-17 | 山西黄河中药有限公司 | Granular traditional Chinese medicine for improving ovarian reserve function and preparation method thereof |
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