CN113230247A - Application of loganin aglycone in preparation of drugs for preventing and treating cervical cancer - Google Patents
Application of loganin aglycone in preparation of drugs for preventing and treating cervical cancer Download PDFInfo
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Abstract
The invention belongs to the field of medicines, and relates to application of loganin aglycone in preparation of antitumor drugs, wherein the tumors specifically relate to gastric cancer, liver cancer, esophageal cancer, colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, leukemia, malignant lymphoma, prostate cancer, breast cancer, brain glioma, bile duct cancer, melanoma, kidney cancer, ovarian cancer, endometrial cancer and cervical cancer of mammals, and more specifically relate to gastric cancer, liver cancer, esophageal cancer, colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, leukemia, malignant lymphoma, prostate cancer, breast cancer, brain glioma, bile duct cancer, melanoma, kidney cancer, ovarian cancer, endometrial cancer and cervical cancer of humans. In vivo and in vitro experiments show that loganin aglycone has good inhibition effect on various tumors, shows good anti-tumor growth activity and has great potential for developing anti-tumor medicaments.
Description
The application is a divisional application on the basis of application number 2016103094870, the invention name is loganin aglycone in preparing antitumor drugs.
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of loganin aglycone in preparation of antitumor medicines.
Background
Malignant tumor is a disease that causes the sudden variation of cell DNA under certain conditions, resulting in uncontrolled cell division, thereby generating continuous proliferation and metastasis, and finally leading to the death of host. Currently, the clinically available methods for treating malignant tumors include surgery, radiotherapy, thermotherapy, chemotherapy, gene therapy, immunotherapy, and the like. Although the prior art has shown that it is possible to treat malignant tumors with different techniques and treatments within limited capabilities, these techniques and treatments all have some significant drawbacks. For example, chemotherapy, the primary treatment, has limited antitumor activity, high toxic side effects, poor patient tolerance and high cost. Therefore, the prevention of the occurrence and development of tumors by the research of chemical antitumor substances in natural plants has become an important field of tumor chemoprevention research and is receiving general attention from the scientific communities all over the world.
Cornus officinalis (Cornus officinalis Sieb.) & Zucc.) is deciduous tree or shrub of Cornus genus of cornaceae family, and is widely distributed in shanxi, gansu, shandong, jiangsu, zhejiang, anhui, jiangxi, hennan, hunan, etc. of China, and also distributed in korean and japan. The dried mature pulp is the Chinese medicine cornus officinalis, also named cornus officinalis, cornus officinalis and the like, and is collected in the 2010 version of the Chinese pharmacopoeia. Can be used for treating vertigo, tinnitus, soreness of waist and knees, sexual impotence, spermatorrhea, enuresis, frequent micturition, metrorrhagia, leukorrhagia, sweating, internal heat, and diabetes. The traditional Chinese medicine composition is widely used clinically, is the main medicine of various compounds or patent medicines such as a pill of six ingredients with rehmannia, a pill of Zhibai with rehmannia, a pill of Jinkui with kidney qi, a pill of Zuogui, a pill of medlar, chrysanthemum and rehmannia, a pill of Guifu with rehmannia, a pill of Yiming with rehmannia, a pill of Jiyin with rehmannia and the like, and is a medicine for tonifying liver and kidney with great research and development values.
Iridoid glycoside is one of the main active ingredients of the traditional Chinese medicine dogwood, and the biological activity of the iridoid glycoside is mainly focused on the aspects of immunoregulation, blood sugar reduction, anticoagulation, memory improvement and the like. Through systematic chemical composition research, 19 iridoid glycoside compounds are found in the traditional Chinese medicine dogwood at present. Loganin is the main component of iridoid glycoside in the Chinese medicine dogwood, is one of the main effective components of Liuwei Dihuang Wan and the like which play pharmacological actions, has the content of 0.37 to 1.22 percent in the medicinal materials, has the functions of immunoregulation, anti-inflammation, antibiosis, cough relieving, phlegm eliminating and the like, and is also an important raw material of some Chinese patent medicines. Loganin aglycone loganin (loganin) has the following structure:
the loganin aglycone was obtained by extraction from leaves of Desfontainia spinosa plants using conventional column chromatography techniques (Peter J. Houghton. Iridoids from Desfontinania spinosa. Phytochemistry,1985,24(8): 1841-1842). The method is complicated to operate, long in time consumption, high in price and not economically feasible. Anupam Maurya and the like optimize a preparation method of loganin aglycone, which takes a chickenaf as a raw material and adopts a rapid centrifugal separation chromatography technology to prepare the loganin aglycone with high purity. The document discloses that loganin itself has no antibacterial activity, but the use in combination with nalidixic acid can significantly reduce the minimum inhibitory concentration of nalidixic acid-resistant and nalidixic acid-sensitive strains of escherichia coli. Loganin aglycone is useful in the treatment of multidrug resistant gram negative bacterial infections (Anupam Maurya. Preparative Isolation of Bioenhancer loganin from Alstonia scholaris by Fast Central functional Partition chromatography separation Science and Technology, 2014,49(5): 773-) 777).
So far, no research on the antitumor biological activity or clinical application of loganin aglycone is available.
Disclosure of Invention
The invention aims to provide application of loganin aglycone in preparing anti-tumor drugs. In the application, the treatment object of the medicament is a mammal or a human, and the specific tumors include but are not limited to gastric cancer, liver cancer, esophageal cancer, colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, leukemia, malignant lymphoma, prostatic cancer, breast cancer, brain glioma, cholangiocarcinoma, melanoma, renal cancer, ovarian cancer, endometrial cancer and cervical cancer.
The applicant researches the anti-tumor effect of loganin through a large number of experiments, and in vitro tumor inhibition experiments find that loganin with different concentrations can treat human gastric cancer MGC-803, human liver cancer HepG-2, human esophageal cancer ECA-109, human colon cancer HCT116, human pancreatic cancer ANC-1, human lung cancer A549, human nasopharyngeal cancer CNE-2, human chronic myelogenous leukemia K562, human malignant lymphoma ATCC, human prostate cancer PC-3, human breast cancer PANC-1, mouse sarcoma S180, rat brain glioma C6, human bile duct cancer QBC939, melanoma B16, renal cancer 786-O, thyroid cancer TPC-1, ovarian cancer SKOV3, endometrial cancer RL95-2, cervical cancer CaSki, larynx cancer HEP-2 and oral cancer SAS 72h, can inhibit the proliferation of the tumor cells in a concentration-dependent manner, and the IC of the loganin can inhibit the proliferation of the cells50At 0.12-50.23. mu.M/ml, the effect of loganin aglycone in inhibiting tumor cell proliferation is stronger than that of positive control drug 5-Fu. The applicant finds that loganin aglycone can inhibit the growth of four tumor cells in a concentration-dependent manner through in-vivo tests on S180 mouse sarcoma, gastric cancer MGC-803, liver cancer HepG-2 and lung cancer A549, the highest tumor inhibition rates are respectively 70.2%, 71.6%, 71.8% and 72.2%, and the highest tumor inhibition rates are obviously higher than respective positive control drugs.
Specifically, the loganin aglycone is 10mg/kg-2000mg/kg, and the loganin aglycone is 1mg/kg-200mg/kg in conversion of human dosage.
The invention also aims to provide a pharmaceutical preparation of loganin aglycone for resisting tumor, which is characterized in that loganin aglycone is used as an effective component and is matched with pharmaceutic adjuvant to be prepared into injection, tablets, capsules and granules according to a conventional preparation method in pharmacy. Pharmacodynamic tests show that each preparation of loganin aglycone has obvious anti-tumor effect.
The preparation containing loganin aglycone is realized by the following technical scheme:
1) the injection is prepared by dissolving loganin bulk drug of the prescription amount in the mixed solvent of the prescription amount, preparing the injection according to the conventional method for preparing the injection in pharmacy, and controlling the weight/volume percentage of loganin in the injection to be 0.01-10%.
2) The preparation method of the tablet comprises the steps of uniformly mixing loganin aglycone and auxiliary materials of microcrystalline cellulose and sodium carboxymethyl starch, adding a proper amount of starch slurry to prepare a soft material, and then sieving the soft material with a 16-mesh sieve for granulation. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, sieving to obtain fine powder, mixing with magnesium stearate, mixing with dry granules, and tabletting.
3) The preparation of the capsule takes loganin aglycone raw material medicine and medical auxiliary material dextrin, evenly mixes the raw material medicine and the medical auxiliary material dextrin, and prepares the capsule according to the conventional method for preparing the capsule in pharmacy.
4) The preparation of the granules is that loganin, starch, dextrin and sucrose powder in the prescription amount are weighed and mixed evenly. Adding appropriate amount of 80% ethanol into the mixed powder, mixing, making soft mass, sieving with 18 mesh nylon sieve to obtain wet granules, drying at about 60 deg.C, sieving with 20 mesh sieve, and packaging.
Compared with the prior art, the invention has the following technical advantages:
1. the antitumor effect is obvious, and the in vivo tests of S180 mouse sarcoma, gastric cancer MGC-803, liver cancer HepG-2 and lung cancer A549 find that loganin aglycone has obvious inhibition effect on the four tumors, and the inhibition effect on the tumors is better than that of the respective positive drugs cyclophosphamide, tegafur and fluorouracil.
2. The anti-tumor range is wide, and in vitro tests show that loganin aglycone has good inhibition effects on gastric cancer, liver cancer, esophageal cancer, colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, leukemia, malignant lymphoma, prostate cancer, breast cancer, brain glioma, cholangiocarcinoma, melanoma, renal cancer, ovarian cancer, endometrial cancer and cervical cancer.
3. The loganin is a natural anti-tumor substance extracted from dogwood, has low toxic and side effects compared with the existing chemotherapeutic drugs, relieves the pain of the chemotherapeutic drugs to patients due to the toxic and side effects, and improves the life quality of the patients.
4. Compared with the existing chemotherapeutic drugs, loganin has obvious price advantage and can reduce the economic burden of patients.
Detailed Description
The present invention is further illustrated below by specific examples in order to provide those skilled in the art with a full understanding of the present invention, but it should be understood by those skilled in the art that the examples of the present invention are not to be construed as limiting the present invention in any way.
Example 1 loganin aglycone tablets
The preparation process comprises mixing loganin aglycone with adjuvants including microcrystalline cellulose and sodium carboxymethyl starch, adding appropriate amount of starch slurry to make soft mass, sieving with 16 mesh sieve, and granulating. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, sieving to obtain fine powder, mixing with magnesium stearate, mixing with dry granules, and tabletting to obtain tablet of about 200 mg.
Example 2 loganin aglycone capsules
Loganin aglycone 10g
Microcrystalline cellulose 300g
Silica gel micropowder 12g
The preparation process comprises the following steps: pulverizing loganin, microcrystalline cellulose and silica gel micropowder, sieving with 100 mesh sieve, mixing, and directly encapsulating.
Example 3 loganin aglycone granules
The preparation process comprises the following steps: weighing loganin, starch, dextrin and sucrose powder according to the prescription amount, and uniformly mixing. Adding appropriate amount of 80% ethanol into the mixed powder, mixing, making soft mass, sieving with 18 mesh nylon sieve to obtain wet granules, drying at about 60 deg.C, sieving with 20 mesh sieve, and packaging.
Example 4 loganin aglycone injection
The preparation process comprises the following steps: mixing ethanol and tween-80, adding loganin, stirring for dissolving, adding water for injection to 10L, stirring, adding 0.5% injectable active carbon, stirring, and removing carbon.
Example 5 loganin aglycone injection
Loganin aglycone 10g
Ethanol 3.3L
Adding water for injection to 10L
The preparation process comprises the following steps: adding loganin into ethanol, stirring to dissolve, adding water for injection to 10L, stirring, adding 0.5% injectable activated carbon, stirring, and removing carbon.
Example 6 loganin aglycone injection
The preparation process comprises the following steps: uniformly mixing the propylene glycol and the ethanol according to the prescription amount, adding loganin aglycone, stirring and dissolving, adding the sodium chloride solution with the concentration of 0.9% according to the prescription amount, uniformly stirring, adding the activated carbon for injection with the concentration of 0.5%, stirring, and removing carbon to obtain the product.
Example 7 loganin aglycone injection
The preparation process comprises the following steps: adding loganin aglycone into PEG-400, stirring for dissolving, adding 0.9% sodium chloride solution to 10L, stirring, adding 0.5% active carbon for injection, stirring, and removing carbon.
Example 8 loganin aglycone injection
The preparation process comprises the following steps: adding loganin aglycone into PEG-400, stirring for dissolving, adding 0.9% sodium chloride solution to 10L, stirring, adding 0.5% active carbon for injection, stirring, and removing carbon.
Example 9 in vitro tumor inhibition by loganin aglycone
1. Tumor cell line for test
Human gastric cancer MGC-803, human liver cancer HepG-2, human esophageal cancer ECA-109, human colon cancer HCT116, human pancreatic cancer ANC-1, human lung cancer A549, human nasopharyngeal cancer CNE-2, human chronic myelogenous leukemia K562, human malignant lymphoma ATCC, human prostate cancer PC-3, human breast cancer PANC-1, mouse sarcoma S180, rat brain glioma C6, human bile duct cancer QBC939, melanoma B16, renal cancer 786-O, thyroid cancer TPC-1, ovarian cancer SKOV3, endometrial cancer RL95-2, cervical cancer CaSki, laryngeal cancer HEP-2 and oral cancer SAS were all purchased from Shanghai cell banks of Chinese academy of sciences.
2. Test method
Taking tumor cells in logarithmic growth phase, and adjusting cell density to 1-4 × 103Per well embedded 96 well culture plate. After 24h of culture, loganin and positive control 5-fluorouracil with different concentrations are added, three multiple wells are arranged at each concentration, and a negative control well and a blank control well are arranged at the same time. Placing at 37 deg.C with 5% CO2The culture was continued in the cell culture chamber for 72 hours.
Adherently growing tumor cells: after the supernatant was aspirated and carefully washed twice with PBS, 100. mu.l of serum-free medium containing 10% MTT (5mg/ml) was added to each well, and the culture was continued for 4 hours. The supernatant was aspirated off and 100. mu.l of dimethyl sulfoxide (DMSO) was added to each well.
Suspension-grown tumor cells: mu.l MTT (5mg/ml) was added to each well and incubation was continued for 4 h. Centrifuge at 1000rpm/min for 10min, carefully aspirate the supernatant and add 100. mu.l of dimethyl sulfoxide (DMSO) per well.
The crystals were completely dissolved by shaking for 10 minutes, and the absorbance (A value) of each well was measured at a wavelength of 570nm using a microplate reader. The inhibition rate of loganin aglycone on different tumor cells is respectively calculated according to the following formula:
the inhibition rate was (1-test OD value/control OD value) × 100%.
IC50The values were calculated by the LOGIT method.
3. Test results
Treating various human tumor cells with loganin aglycone of different concentrations for 72h to inhibit proliferation of each tumor cell and IC of the tumor cells50At 0.12 μ M/ml to 50.23 μ M/ml, loganin aglycone has stronger effect on inhibiting tumor cell proliferation than 5-Fu (Table 1).
TABLE 1 inhibition of loganin and 5-Fu tumor cells
4. And (4) conclusion:
loganin aglycone has obvious effect of inhibiting proliferation of a plurality of tumor cell strains cultured in vitro.
Example 10 inhibition of loganin in vivo against mouse sarcoma S180
1. Tumor cell line for test
S180 murine sarcoma cell strain purchased from Shanghai Living sciences research institute of Chinese academy of sciences
2. Animal for test
The ICR mouse Beijing Witonglihua laboratory animal technology company Limited produces license number: SCXK (Jing) 2012 0001-
3. Test method
Conventional culture and passage of mouse sarcoma S180 cell, taking log-phase growth phase cell, detecting cell activity by trypan blue staining method, and regulating viable cell concentration to 1 × 107The vaccine is inoculated to the armpit of a nude mouse according to the dosage of 0.2ml per mouse. After the tumor grows out of the armpit of the nude mouse, the tumor is removedNude mice were randomly divided into 5 groups: model control group, positive drug group, low loganin aglycone (100mg kg)-1) Middle (150mg kg)-1) High dose (200 mg. kg)-1) And (4) grouping. The model group is administered with 0.9% NaCl solution with the same volume by intragastric administration, and the positive drug cyclophosphamide group is 150mg kg-1The preparation is administered by intraperitoneal injection, each group of loganin aglycone is administered by intragastric administration according to the designed dose once a day, and the test is finished after 60 days.
Animals were sacrificed 24h after the last dose, tumors were weighed and the mean tumor inhibition rate (I) was calculated as follows: i ═ 100% (1-mean tumor weight in dosing group/mean tumor weight in model group) ×
4. Data statistics and processing method
The experimental data are analyzed by adopting a sps 16.0 and a one way ANOV with a one-way variance, and the difference is statistically significant when p is less than 0.05.
5. Test results and conclusions
TABLE 2 loganin aglycone in vivo inhibition of murine sarcoma S180 results
In comparison to the set of models,##P＜0.01；
compared with the positive control group, the composition has the advantages that,※P＜0.05
as can be seen from Table 2, loganin aglycone can effectively inhibit the growth of murine sarcoma S180, the inhibition effect is concentration-dependent, and the inhibition rate (58.9%, 70.2%) of the medium-high concentration group is obviously higher than that of the positive control drug cyclophosphamide group (51.4%).
Example 11 inhibition of loganin aglycone in vivo against human gastric carcinoma MGC-803
1. Tumor cell line for test
MGC-803 human gastric cancer cell strain purchased from Shanghai Living science research institute of Chinese academy of sciences
2. Test animal
BALB/c nude mouse Beijing Witonglihua laboratory animal technology Limited produces license number: SCXK (Jing) 2012 0001-
3. Test method
Conventional culture and passage of human gastric cancer MGC-803 cell, taking logarithmic growth phase cell, regulating living cell concentration to 1 x 1070.2ml of each mouse, and is inoculated to the armpit of a nude mouse. After the tumor grows out of the armpit of the nude mice, the tumor-bearing nude mice are randomly divided into 5 groups according to the tumor size: model group, positive medicine group, low loganin aglycone (100mg kg)-1) Middle (150mg kg)-1) High dose (150 mg/kg)-1) And (4) grouping. The model group is administered with 0.9% NaCl solution with the same volume by gavage, the positive drug tegafur group is administered with 12mg/kg by gavage, the loganin group is administered with gavage once a day according to the designed dosage, and the test is finished after 60 days.
Animals were sacrificed 24h after the last dose, tumors were weighed and the mean tumor inhibition rate (I) was calculated as follows: i ═ 100% (1-mean tumor weight in dosing group/mean tumor weight in model group).
4. Data statistics and processing method
The experimental data are analyzed by adopting a sps 16.0 and a one way ANOV with a one-way variance, and the difference is statistically significant when p is less than 0.05.
5. Test results and conclusions
TABLE 3 inhibition of loganin aglycone in vivo against human gastric carcinoma MGC-803
In comparison to the set of models,##P＜0.01；
compared with the positive control group, the composition has the advantages that,※P＜0.05
as can be seen from Table 3, loganin can effectively inhibit the growth of gastric tumors, the inhibition effect is concentration-dependent, and the inhibition rate (71.6%) of the high-concentration group is obviously higher than that of the positive control drug tegafur group (57.2%).
Example 12 in vivo inhibition of loganin to human liver cancer HepG-2
1. Tumor cell line for test
Human liver cancer HepG-2 cell strain purchased from Shanghai Life science research institute of Chinese academy of sciences
2. Test animal
The 5-week-old female BALB/c nude mice, Beijing Witonglihua laboratory animal technology company, produces license numbers: SCXK (Jing) 2012 0001-
3. Test method
The HepG2 cells of human liver cancer are cultured and passaged conventionally, and 0.2ml of 3.5 multiplied by 10 subcutaneous inoculation is carried out on the cells in logarithmic growth phase at the neck and the back of each mouse7The tumor cell suspension of each/ml is used for measuring the tumor diameter of the nude mice by a vernier caliper every day, and after the tumor of each mouse grows to 100-300 mm, the tumor cell suspension is randomly divided into 5 groups according to the body mass and the tumor mass volume, and each group comprises 8 mice. The dosage groups are respectively 100 mg/kg per day-1、150mg·kg-1、150mg·kg-1Gavage administration of loganin aglycone solution, administration of pure water to model control group at the same time and in the same manner, and administration of 20 mg/kg/day for positive control group-1The medicine is administrated by intraperitoneal injection. Measuring the diameter of the tumor after the administration every day, finishing the feeding after the continuous administration for 21 days, killing the animals, weighing the body mass, picking up tumor blocks, weighing, and calculating the tumor inhibition rate. Tumor inhibition rate (average tumor mass in control group-average tumor mass in test group)/average tumor mass in control group × 100%.
4. Data statistics and processing method
The experimental data are analyzed by adopting a sps 16.0 and a one way ANOV with a one-way variance, and the difference is statistically significant when p is less than 0.05.
5. Test results and conclusions
TABLE 4 results of in vivo inhibition of loganin aglycone on human hepatoma HepG-2
In comparison to the set of models,##P＜0.01；
compared with the positive control group, the test results show that,※P＜0.05
as can be seen from Table 4, loganin can effectively inhibit the growth of hepatoma carcinoma cells, the inhibition effect is concentration-dependent, and the inhibition rate of the high-concentration group (58.7%, 71.8%) is obviously higher than that of the positive control fluorouracil group (50.8%).
Example 13 in vivo inhibition of loganin aglycone to human Lung carcinoma A549
1. Tumor cell line for test
Human lung cancer cell strain A549 purchased from Shanghai Life science research institute of Chinese academy of sciences
2. Test animal
The 5-week-old female BALB/c nude mice, Beijing Witonglihua laboratory animal technology company, produces license numbers: SCXK (Jing) 2012 0001-
3. Test method
Culturing human lung cancer cell A549 in DMEM culture solution containing 10% fetal calf serum, and collecting cells in logarithmic growth phase, 1 × 106A549 cells/0.2 mL are inoculated in the armpits of nude mice, the growth of tumors can be seen after 1-2 weeks, the tumor diameter of the nude mice is measured by a vernier caliper every day, and after the tumors of each mouse grow to 100-300 mm, the tumors are randomly divided into 5 groups according to the body mass and the tumor mass volume, and each group comprises 8 mice. The dosage groups are respectively 100 mg/kg per day-1、150mg·kg-1、150mg·kg-1Gavage administration of loganin aglycone solution, administration of pure water in the same volume for model control group at the same time and manner, and administration of 150 mg/kg for positive drug cyclophosphamide group-1The medicine is administrated by intraperitoneal injection. Measuring the diameter of the tumor after the administration every day, finishing the feeding after the continuous administration for 21 days, killing the animals, weighing the body mass, picking up tumor blocks, weighing, and calculating the tumor inhibition rate. Tumor inhibition rate (average tumor mass in control group-average tumor mass in test group)/average tumor mass in control group × 100%.
4. Data statistics and processing method
The experimental data are analyzed by adopting a sps 16.0 and a one way ANOV with a one-way variance, and the difference is statistically significant when p is less than 0.05.
5. Test results and conclusions
TABLE 5 inhibition of loganin aglycone in vivo on human lung carcinoma A549
In comparison to the set of models,##P＜0.01；
harmonizing yangThe comparison of the sexual comparison group is carried out,※P＜0.05
as can be seen from Table 5, loganin can effectively inhibit the growth of lung cancer cells, the inhibition effect is concentration-dependent, and the inhibition rate (72.2%) of the high-concentration group is obviously higher than that of the positive control drug fluorouracil group (55.6%).
In addition, human esophageal cancer ECA-109, human colon cancer HCT116, human pancreatic cancer ANC-1, human nasopharyngeal cancer CNE-2, human chronic myelocytic leukemia K562, human malignant lymphoma ATCC, human prostate cancer PC-3, human breast cancer PANC-1, rat brain glioma C6, human bile duct cancer QBC939, melanoma B16, renal cancer 786-O, thyroid cancer TPC-1, ovarian cancer SKOV3, endometrial cancer RL95-2, cervical cancer CaSki, laryngeal cancer HEP-2, oral cancer SAS and other human tumor strains are used for in vivo tests, and loganin has a good inhibition effect on the tumors.
Claims (5)
1. Application of loganin aglycone in preparing medicine for preventing and treating cervical cancer is provided.
2. The use according to claim 1, wherein the loganin is administered in a human dose of from 1mg/kg.d to 200 mg/kg.d.
3. The use of claim 1, wherein loganin is in an oral formulation or an injectable formulation.
4. The use according to claim 3, wherein the oral formulation is a tablet, capsule or granule thereof.
5. The medicament of claim 3, wherein the loganin aglycone is present in an injectable formulation in an amount of 0.01% to 10% w/v.
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| CN202110565637.5A Pending CN113209079A (en) | 2016-05-11 | 2016-05-11 | Application of loganin aglycone in preparation of medicine for preventing and treating esophageal cancer |
| CN202110565636.0A Pending CN113209078A (en) | 2016-05-11 | 2016-05-11 | Application of loganin aglycone in preparation of pancreatic cancer prevention and treatment medicines |
| CN201610309487.0A Active CN107362158B (en) | 2016-05-11 | 2016-05-11 | Application of loganin aglycone in preparation of antitumor drugs |
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| CN107362158B (en) | 2021-07-20 |
| CN113181164A (en) | 2021-07-30 |
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