CN112618569A - Medicine for treating urothelial cancer - Google Patents
Medicine for treating urothelial cancer Download PDFInfo
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- CN112618569A CN112618569A CN202011637448.6A CN202011637448A CN112618569A CN 112618569 A CN112618569 A CN 112618569A CN 202011637448 A CN202011637448 A CN 202011637448A CN 112618569 A CN112618569 A CN 112618569A
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Abstract
The invention discloses a medicament for treating urothelial cancer, which comprises sanguinarine and cisplatin. In the invention, sanguinarine can obviously inhibit EJ cell proliferation, and compared with a Control group, the EJ cell apoptosis in the combined medicine group of sanguinarine and cisplatin is obvious (P is less than 0.05). In a nude mouse subcutaneous tumor formation model, compared with a Control group, the tumor growth of mice in a combined drug group is obviously slowed down, and the apoptosis is obviously increased (P is less than 0.05), and compared with a cisplatin group, the combined drug group can obviously improve the chemotherapy side effects of weight loss, spleen immune organ quality reduction and the like of nude mice. Sanguinarine can inhibit proliferation of EJ cell of bladder cancer, is time-dose dependent, and can induce apoptosis and inhibit growth of bladder tumor. The sanguinarine and cisplatin combined medicine can relieve toxic and side effects of cisplatin chemotherapy and promote tumor cell apoptosis, thereby achieving the effects of synergy and toxicity reduction.
Description
Technical Field
The invention relates to the field of chemotherapy drugs, and in particular relates to a drug for treating urothelial cancer.
Background
Urothelial cancer (uper track Urothelian carcinosa, UTUC) is a multiple malignant tumor that originates in the urothelium, including renal pelvis cancer, ureter cancer, bladder cancer, and urethral cancer, and is the most common tumor of the urinary system. Among them, Bladder Cancer (BC) accounts for about 80% -90% of urothelial Cancer. According to the recent report of the world health organization WHO, the number of new bladder cancer cases worldwide is about 7,4000 every year, which accounts for 7% of the total number of all new tumors, and the death rate is rising and accounts for 4% of the death rate of all malignant tumors. Cystotomy or nephroureterectomy are one of the gold criteria for the treatment of urothelial tumors, but for patients at high risk for tumors, local recurrence or distant metastasis after surgery is the major cause of no improvement in long-term survival. In the bladder cancer diagnosis and treatment guidelines, the recommended first-line drug therapy is mainly Cisplatin (Cis) based chemotherapy, but the recurrence of tumors and the side effects and drug resistance in treatment do not significantly increase the 5-year survival rate of bladder cancer patients. Aiming at the current treatment status of bladder cancer, how to enhance chemotherapy sensitivity and improve chemotherapy side effects and drug resistance to improve the curative effect of chemotherapy is a hotspot of current research, and has important significance for improving the survival rate of urothelial cancer patients, particularly bladder cancer patients and improving prognosis.
Accordingly, the prior art is yet to be improved and developed.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a medicament for treating urothelial cancer, and aims to solve the problems that the single use of cisplatin as a bladder cancer chemotherapeutic drug in the prior art has large side effect, easy tumor recurrence and no increase of survival rate.
The technical scheme of the invention is as follows:
a medicine for treating urothelial cancer contains sanguinarine and cisplatin.
The medicament for treating urothelial cancer, wherein the urothelial cancer comprises renal pelvis cancer, ureteral cancer, bladder cancer and urethral cancer.
The medicament for treating the urothelial cancer further comprises a pharmaceutically acceptable carrier.
The medicine for treating the urothelial cancer is an oral preparation, an injection, a transdermal preparation, a subcutaneous embedding preparation or an infusion medicine.
The medicament for treating the urothelial cancer comprises the steps of inhibiting proliferation of urothelial cancer cells and promoting apoptosis of the urothelial cancer cells.
The medicament for treating the urothelial cancer is characterized in that the therapeutic dosage range of the sanguinarine is as follows: 10mg/kg-50 mg/kg; the therapeutic dose range of cisplatin is: 50-100mg/m2。
Has the advantages that: the medicine for treating urothelial cancer provided by the invention comprises Sanguinarine (Sanguinarine, Sang) and Cisplatin (cissplatin, Cis). The CCK-8 method was used to detect the proliferation of EJ cells from bladder cancer treated with different concentrations of Sang and to calculate the IC50 values. Detecting the apoptosis conditions of a Control group, a Sang group, a Cis group and a combined medicine group by using an Annexin V FITC/PI method; constructing a nude mouse subcutaneous tumor formation model, respectively carrying out tail vein injection and administration of physiological saline, Sang, Cis and combined administration, observing the survival state of the nude mouse in the experimental process, detecting the tumor inhibition rate, observing pathological changes by HE staining, and observing the apoptosis condition of tumor cells by TUNEL staining. The results show that: the Sang can obviously inhibit the EJ cell proliferation, and compared with the Control group, the EJ cell apoptosis of the combined drug group is obvious (P < 0.05). In a nude mouse subcutaneous tumor formation model, compared with a Control group, the tumor growth of mice in a combined drug group is obviously slowed down, the apoptosis is obviously increased (P is less than 0.05), and compared with a Cis group, the combined drug group can obviously improve the chemotherapy side effects of weight loss, spleen immune organ quality reduction and the like of nude mice. Sang can inhibit proliferation of EJ cells of bladder cancer, is time-dose dependent, and can induce EJ cell apoptosis and inhibit bladder tumor growth. The combination of Sang and Cis can reduce the toxic and side effects of Cis chemotherapy and promote tumor cell apoptosis, thereby achieving the effects of synergy and attenuation.
Drawings
FIG. 1 is a graph showing the results of inhibition of human bladder cancer EJ cell proliferation by sanguinarine.
FIG. 2A is a diagram of the apoptosis of EJ cells of bladder cancer in the Control group, the Sangg group, the Cis group and the combination group obtained by flow cytometry analysis according to the present invention.
FIG. 2B is a graph showing a comparison of the apoptosis rates of EJ cells in the Control group, the Sang group, the Cis group and the combination group.
FIG. 3A is a graph showing the body weight changes of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 3B is a graph showing the change in body weight of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group after treatment.
FIG. 3C is a graph showing the change in spleen weight of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 3D is a graph showing the change in liver weight of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 4 is a graph showing the change in tumor volume of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 5 is a graph showing the tumor morphology change of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 6 is a graph showing the comparison of tumor weights of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 7 is a graph showing the comparison of tumor suppression rates of tumor-bearing mice in the Control group, the Sang group, the Cis group and the combination group.
FIG. 8 is a graph of pathological results of HE staining and TUNEL fluorescent staining of tumor tissue.
Detailed Description
The present invention provides a drug for treating urothelial cancer, which is described in further detail below in order to make the objects, technical solutions and effects of the present invention clearer and clearer. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Bladder cancer is a common urothelial tumor and has the characteristic of drug resistance and easy recurrence. The clinical treatment is mainly surgical treatment assisted by platinum drug chemotherapy. Cisplatin is used as a cell non-specific chemotherapeutic drug, has a wide anti-tumor spectrum, is an important chemotherapeutic drug for treating transitional cell cancer, has the total reaction rate of cisplatin single-drug chemotherapy of about 40 percent, has large toxic and side effects and poor patient prognosis, and is particularly important for searching a new drug to enhance the chemotherapeutic effect of bladder cancer and reduce the side effects of chemotherapy. The research of the compounds and derivatives thereof from natural medicine sources shows that the compounds and derivatives thereof have the anti-tumor effect, and the anti-tumor activity of the compounds and derivatives thereof is deeply excavated, so that the compounds and derivatives thereof become important anti-tumor adjuvant therapy medicines and have practical values.
At present, a large number of natural products with direct or indirect inhibition effects on tumors are found from Chinese herbal medicines, and the natural products have great potential for developing novel chemotherapeutic drugs or treatment modes as a lead, and a batch of drugs such as paclitaxel, vinblastine and the like are successfully marketed. Sanguinarine (Sang) is widely present in plants of Chelidonium of Papaveraceae, and is the main active ingredient of herba Chelidonii, herba Macleayae Cordatae, and herba Saxifragae. Sanguinarine as benzophenanthridine alkaloid with molecular formula of C20H14NO4The chemical structural formula is
The sanguinarine has the effects of oxidation resistance, tumor resistance, virus resistance, bacteria resistance and the like, however, the research on the effect and mechanism of the sanguinarine on bladder cancer is rarely reported, and the potential of the sanguinarine as a novel chemotherapeutic drug for development is worthy of further digging.
Based on the above, the invention provides a medicament for treating urothelial cancer, which comprises sanguinarine and cisplatin. In some embodiments, it further comprises some pharmaceutically acceptable carriers. In some embodiments, the drug is an oral formulation, an injection, a transdermal formulation, a subcutaneous implant formulation, or an infusion drug, but is not limited thereto.
In some embodiments, the urothelial cancer includes, but is not limited to, renal pelvis cancer, ureteral cancer, bladder cancer, and urethral cancer.
In some embodiments, the therapeutic dose range of sanguinarine is: 10mg/kg-50 mg/kg; therapeutic agents for cisplatinThe amount ranges are: 50-100mg/m2。
The invention takes human bladder cancer EJ cells as research objects, discusses the synergistic attenuation effect of the combination of the Sangg and the Cis on the bladder cancer chemotherapy from the levels of cells and animals respectively, initially discloses the action mechanism of the EJ cells, and provides reference and data support for the development of sanguinarine as a novel chemotherapeutic medicament and the clinical treatment of bladder cancer.
The following examples demonstrate and explain the mechanism of a drug for treating urothelial cancer according to the present invention:
examples
The drugs and reagents provided by this example are:
sang (Chemfaces, USA); cis (Sigma, usa); RPMI 1640 medium, fetal bovine serum, trypsin, penicillin-streptomycin mixture (Gibco, USA); CCK-8 kit, Annexin V FITC/PI apoptosis detection kit (Beijing Quanjin Biotech company); TUNEL kit (Roche, switzerland).
The main instruments that this embodiment provided do:
BB 150 carbon dioxide incubator, X3R table-type high-speed large-capacity centrifuge, Multiskan Go1510 full-wavelength microplate reader (Thermo corporation, USA); ckx41 inverted microscope (Olympus, japan); FACSCalibur flow cytometer (BD Co., USA).
The cell and animal sources used in this example:
human bladder cancer EJ cells were purchased from the chinese academy of sciences typical culture collection committee cell bank and stored for a long period in this laboratory. SPF-grade BALB/c nude mice, female, 4-5 weeks old, 40, 15 +/-3 g of body mass, purchased from Beijing Wittingle laboratory animal technology Co., Ltd, and having the qualification number of SCXK (Jing) 2016-.
The experimental method provided by the embodiment is as follows:
1. cell culture:
EJ was performed when cells were grown to log phase and in good condition.
2. CCK-8 detects cell proliferation:
cells were seeded in 96-well plates, different concentrations of Sang were set up, 3 replicates per group, cells were treated for 24h and 48h, and cells were treated according to CCK8 kit instructions. The EJ cell viability and half maximal inhibitory concentration (IC 50) were calculated for each group. Cell viability (%) ([ a (additive) -a (blank) ]/[ a (Control) -a (blank) ] × 100%
3. Annexin V FITC/PI detection of apoptosis:
bladder cancer EJ cells were treated with Sang (3.0 μmol/L), Cis (0.5ug/mL) and Sang (1.5 μmol/L) + Cis (0.25ug/mL) separately for 24h cells were treated according to the apoptosis kit instructions and FlowJo software was used for results analysis. The apoptosis rate is the early apoptosis rate + the late apoptosis rate.
4. Modeling, grouping, administration and antitumor efficacy evaluation:
female BALB/c SPF-grade nude mice 40 were housed in an SPF laboratory, and the nude mice were randomly divided into 4 groups, namely, Control (saline) group, Sang (20mg/kg) group, Cis (5mg/kg) group, and Sang (10mg/kg) combined Cis (2.5mg/kg) group. Each group had 10. Constructing a nude mouse subcutaneous tumor model, inoculating 125uL EJ cell suspension (1 × 10) in the right axilla of the mouse7cell/only). Tumor volume was measured every other day, V ═ 2 (a × B2)/where a is long and B is wide. When the tumor grows to 50mm3Administration is initiated. Each group was administered 5 times by tail vein injection of 200uL of the corresponding drug once every 3 days, and the last administration was followed by a week observation. 1) General state observation of mice: in the experimental process, the living state, spirit, activity, food intake, skin and other general conditions of the nude mice are observed every other day. 2) And (3) detecting the tumor inhibition rate: one week after the last dose was observed. After observation (experiment day 33), the body mass of each group of mice was weighed, anesthetized, the eyeball was removed to obtain blood, the mice were sacrificed by cervical discission, the tumor mass was peeled off and the tumor mass was weighed, and the tumor inhibition rate was calculated. 3) Spleen and liver were separated and the mass was weighed and organ coefficients were calculated. 4) Detection of HE pathology: fresh tissue of the specimen of heart, liver, spleen, lung and kidney and tumor is taken to be prepared into a section, HE staining is carried out, and the morphological change of the section tissue is observed under an inverted fluorescence microscope. 5) Tumor tissue apoptosis detection: collecting fresh tumor sample, processing, slicing, and detecting with TUNEL apoptosis detection kitAnd (5) measuring and judging the apoptosis condition of the tissue.
Tumor inhibition rate/% (Control group average tumor mass-administration group average tumor mass)/(Control group average tumor mass) × 100
Organ coefficient (organ mass/body weight)
5. The statistical method comprises the following steps:
statistical analysis was performed using SPSS17.0 software and GraphPad Prism7 software, data are expressed as mean. + -. standard deviation (+ -s), comparisons between two groups were performed using t-test, P <0.05 representing statistical significance.
6. Experimental results and analysis:
6.1 Hematodine proliferation inhibitory Effect on bladder cancer cells:
the results of the CCK-8 experiments with 24h and 48h EJ cells treated with non-concentrated Sang show that Sang significantly inhibited cell proliferation (P <0.05) and was time-dependent and dose-dependent, compared to Control, after treatment with EJ cells in the Sang group, as shown in FIG. 1. The IC50 for the 24h and 48h of the Sang group treated EJ cells was calculated by Graphpad software to be 3.0. mu. mol/L and 1.6. mu. mol/L and used as a reference for subsequent experimental concentrations.
6.2 inhibitory Effect of Sanguinarine in combination with cisplatin on bladder cancer
As a result of Annexin V FITC/PI (shown in FIGS. 2A and 2B), the ratio of apoptotic cells in Control group was (2.17. + -. 0.87)%, that in Sang group was (16.83. + -. 4.62)%, that in Cis group was (26.34. + -. 1.03)%, and that in drug combination was (37.07. + -. 4.02)%. Compared with the Control group, the Sang group has a remarkably increased proportion of apoptosis (P is less than 0.001), and compared with the Control group, the Cis group and the combination group have a remarkably increased proportion of apoptosis (P is less than 0.001).
6.3 attenuation of tumor-bearing mice by combination of sanguinarine and cisplatin
Before the experiment, all the nude mice have good states, no statistical difference in body mass, healthy pink skin, sensitive reaction and normal diet. After the tumor inoculation is successful, the tumor volume is gradually increased, the appearance is spherical, and the mass of the first administration body is not different among groups. Compared with the Control group, the Cis group mice showed side effect symptoms on the 20 th day of the experiment, and the symptoms of general listlessness, reduced activity, tendency to crouch and gather together, white, rough and glossy skin, back arching, obvious decline of body mass, individual eyelid swelling and the like. On the 28 th day of the experiment, the Sang group and the drug combination group showed similar symptoms, and the degree was mild, the mental state and the activity were still adequate, and the physical quality was on the rising trend. During the administration period, the quality of the Sang group is not obviously different from that of the Control group, the quality of the Cis group is obviously reduced (P is less than 0.001) compared with that of the Control group, the quality of the combined drug group is reduced to a certain extent (P is less than 0.01) compared with that of the Control group, and the quality of the Cis group is obviously different (P is less than 0.001) compared with that of the Cis group. (as shown in fig. 3A and 3B). The combined medicine group has an improvement effect on the condition of the reduction of the physique of Cis group mice and the life quality of tumor-bearing mice. The spleen and liver quality of the Sang group and the combined drug group are not obviously different from those of the Control group; the spleen and liver quality of tumor-bearing mice in the Cis group is obviously reduced, the spleen quality and the Control group in the Cis group have obvious difference (P is less than 0.001), and the liver quality and the Control group in the Cis group have obvious difference (P is less than 0.001); spleen coefficients and liver coefficients of the mice in each group are respectively calculated according to an organ coefficient formula, and the Cis group has obvious difference and statistical significance (P is less than 0.05) compared with the Control group. The difference between the other groups and the Control group is not significant, and the liver coefficient medicine group and the Control group have no significant difference. The results show that the combined drug group has a certain protective effect on spleen which is an important immune organ of tumor-bearing mice, and has an improvement effect on the weight loss and the survival state of the mice (as shown in figures 3C and 3D, and tables 1 and 2).
TABLE 1 Effect on tumor-bearing mice before and after drug administration: (
n＝6)
*P<0.05 vs Control group
TABLE 2 organ coefficients of tumor-bearing mice: (
n＝6)
*P<0.05 vs Control group
6.4 tumor inhibition of drug combination of sanguinarine and cisplatin on tumor-bearing mice
During the administration period, the tumor volume growth curve (shown in figure 4), the tumor volumes of the Control group, the Sang group and the Cis group and the combined drug group are in the overall rising trend, and the tumor volumes of the combined drug group are significantly different from those of the Control group (P is less than 0.001); after 5 times of administration, the tumor volumes and weights of the Sang group, the Cis group and the combined drug group were all reduced compared with those of the Control group (as shown in fig. 5 and 6), and the tumor masses of the Control group, the Sang group, the Cis group and the combined drug group were respectively as follows: (1.7. + -. 0.2) g, (1.1. + -. 0.2) g, (0.8. + -. 0.1) g, (0.5. + -. 0.2) g. The tumor inhibition rates are 32.23%, 54.82% and 73.32% respectively; compared with the Control group, the tumor inhibition rate of the combined drug group is significantly different (P < 0.001) (as shown in figure 7). From the growth change curve of the tumor volume to the tumor quality and the tumor inhibition rate, the single administration group and the combined administration group have the tumor inhibition effect, the combined administration group has the most obvious anti-tumor effect, and the anti-tumor synergistic effect is achieved.
6.5 Effect of sanguinarine in combination with cisplatin on apoptosis of tumor tissue
As a result of pathological observation of tumor tissue by HE staining (as shown in FIG. 8), the tumor cells in the Control group are densely arranged, the cell nuclei are obvious, and the volume of the tumor cells is large. In the TUNEL apoptosis assay, the increase in the green fluorescence signal of the combination group representing apoptosis compared to the Control group indicates that the combination group induced more apoptosis.
In conclusion, the invention explains that sanguinarine can inhibit the proliferation of bladder cancer cells and promote the apoptosis of EJ cells of bladder cancer, and discovers that mice have obvious chemotherapy side effects compared with a Control group and a combined drug group by constructing a nude mouse subcutaneous tumor formation model, and the sanguinarine and cisplatin combined drug group has obvious advantages in tumor inhibition and mouse survival quality. The mechanism of reducing the side effect of the cisplatin by the combined medication is probably related to the protection effect of the sanguinarine on important immune organs such as spleen and the like of a tumor-bearing mouse. The HE pathological results and TUNEL fluorescent staining results show that the inhibition effect of the sanguinarine and cisplatin combined drug on bladder cancer cell tumor formation is more obvious compared with that of the Sang group and the Cis group, and the inhibition effect is probably realized by further inducing apoptosis. The research finds that sanguinarine has the effects of inhibiting proliferation and promoting apoptosis on EJ cells, and the combination of sanguinarine and cisplatin has obvious attenuation and synergism effects on cell and animal levels compared with the administration of pure cisplatin. The prior research shows that sanguinarine can inhibit the proliferation of various tumor cells. The research on the antitumor of sanguinarine relates to different systems such as respiration, digestion, endocrine, nervous system and the like, and mainly plays a role in inhibiting the growth of tumors by inhibiting cell proliferation, inducing apoptosis, resisting angiogenesis, reversing EMT (acute embryonic Stem cell) progression, inhibiting metastasis, promoting oxidative stress, regulating tumor-related channels and the like. Rahman et al found that sanguinarine induced Reactive Oxygen Species (ROS) -dependent ceramide (Cer) production and Akt dephosphorylation, thereby inducing apoptosis in leukemic cells. Han and other researches find that after sanguinarine acts on bladder cancer cells, the activity of XIAP apoptosis inhibitory protein is reduced, Bax is up-regulated, Bid is down-regulated, Egr-1 is up-regulated, mitochondrial dysfunction is caused, damaged mitochondria stimulate the generation of ROS, and excessive ROS generation activates caspase-3, caspase-8 and caspase-9, so that mitochondria are damaged to induce apoptosis. In addition, sanguinarine can inhibit microtubule polymerization and can insert double-stranded DNA, which is more specific for tumor cells for cytotoxicity and DNA damage. Sanguinarine can also enhance the sensitivity of tumors to chemotherapeutic drugs by participating in the inhibition of ceramide processes. One of the antitumor mechanisms of cisplatin is that cisplatin acts on DNA molecules after entering cell nucleus, interferes with DNA repair mechanism, causes DNA structural change and causes apoptosis. The combined use of sanguinarine and cisplatin can generate double damage to DNA of tumor cells, promote apoptosis and enhance sensitivity to chemotherapeutic drugs, thereby synergistically playing an anti-tumor role and realizing a synergistic effect on bladder cancer chemotherapy.
In the cisplatin chemotherapy process, the most common clinical side effect is gastrointestinal tract reaction, the clinical application of cisplatin is limited by the toxic and side effect of cisplatin, and the reduction of the toxic and side effect by combined medication has important significance for improving the treatment effect and the survival experience of patients. In the research, by establishing a nude mouse subcutaneous transplantation bladder tumor model, the single use of cisplatin is found to have obvious influence on the survival quality of tumor-bearing mice, the weight is obviously reduced, and the tumor cachexia state is presented. The attenuation effect of the sanguinarine and cisplatin combined medicine on the bladder cancer treatment can be realized by improving the body metabolism, enhancing the immune function and the like.
In conclusion, the research finds that sanguinarine has the effects of inhibiting proliferation and promoting apoptosis on EJ cells in the process of the occurrence and the progress of bladder cancer, the synergistic attenuation effect of the combination of sanguinarine and cisplatin on bladder cancer chemotherapy is demonstrated from the cell and animal level, the action mechanism of the sanguinarine is possibly related to the induction of apoptosis, the improvement of body metabolism and immunity, and the research is worth further and deeply discussing.
It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.
Claims (6)
1. A medicament for treating urothelial cancer, comprising sanguinarine and cisplatin.
2. The medicament for treating urothelial cancer according to claim 1, wherein the urothelial cancer includes renal pelvis cancer, ureteral cancer, bladder cancer and urethral cancer.
3. The medicament for treating urothelial cancer according to claim 1, further comprising a pharmaceutically acceptable carrier.
4. The drug for treating urothelial cancer according to claim 1, wherein the drug is an oral preparation, an injection, a transdermal preparation, a subcutaneous implant preparation or an infusion drug.
5. The medicament for treating urothelial cancer according to claim 1, wherein the treatment comprises inhibiting proliferation of urothelial cancer cells and promoting apoptosis of urothelial cancer cells.
6. The medicament for treating urothelial cancer according to claim 1, wherein the therapeutic dosage range of sanguinarine is: 10mg/kg-50 mg/kg; the therapeutic dose range of the cisplatin is as follows: 50-100mg/m2。
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| US20060009506A1 (en) * | 2004-07-09 | 2006-01-12 | Odyssey Thera, Inc. | Drugs for the treatment of neoplastic disorders |
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| CN114712377A (en) * | 2022-04-26 | 2022-07-08 | 江苏师范大学 | Application of clinopodium polycephalum saponin A in preparing medicine |
| CN114712377B (en) * | 2022-04-26 | 2023-08-15 | 江苏师范大学 | Application of clinopodium polycephalum saponin A in preparing medicines |
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