CN116159122A - Application of soybean active peptide in liver cancer treatment process of oxaliplatin - Google Patents
Application of soybean active peptide in liver cancer treatment process of oxaliplatin Download PDFInfo
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Abstract
The invention relates to the field of drug treatment of liver cancer, in particular to the combined use of soybean active peptide in the process of treating liver cancer by oxaliplatin, which is prepared by taking soybean germ membrane as a raw material for hydrolysis, wherein the relative molecular weight of the active peptide is in the range of 400 daL-700 daL, and the active peptide has good biological effect and immunoregulatory activity. The combined use of oxaliplatin and soybean active peptide can effectively enhance the proliferation inhibition effect on liver cancer cells, accelerate the induction of apoptosis of liver cancer cells, relieve secondary drug resistance generated in the treatment process of oxaliplatin, relieve peripheral neuropathy (CIPN) symptoms caused by chemotherapy, repair intestinal mucosal epithelial cell injury, and improve intestinal mucositis symptoms such as nausea, vomiting, diarrhea and the like. Compared with single administration, the combined soybean active peptide can effectively enhance the treatment effect of oxaliplatin on liver cancer diseases and reduce adverse drug reaction.
Description
Technical Field
The invention relates to the technical field of medicaments for treating liver cancer, in particular to a combined use of soybean active peptides in the process of treating liver cancer by oxaliplatin.
Background
The primary liver cancer is taken as the cancer which is primary in liver tissues, and is a malignant tumor with high incidence and great harm in China. The incidence rate of China in the past two decades rises year by year, the proportion of the liver cancer patients in China reaches 50% in global liver cancer patients, the definite diagnosis rate of the liver cancer patients in the same year is close to the death rate, the survival rate of the liver cancer patients is low, the survival quality is poor, and chemotherapy drugs are generally used clinically to assist in treating liver cancer, but the clinical treatment effect of the liver cancer patients is greatly limited due to the problems of great side effects and drug resistance of the human body injury of the chemotherapy drugs.
Oxaliplatin is used as a 3 rd generation platinum anticancer drug and is commonly used for treating liver cancer clinically. However, oxaliplatin has the same problems with other first-line chemotherapeutics, and is easy to cause peripheral neuropathy (CIPN) caused by chemotherapy to patients in the clinical use process, the occurrence rate of CIPN adverse reaction in the patients taking the drugs is up to 30% -40%, and symptoms can be relieved only by reducing the dose of the chemotherapeutics, prolonging the chemotherapy period and stopping the drugs clinically, so that the treatment effect of the drugs is seriously affected. Meanwhile, due to long-term use of the medicine in the treatment process, liver cancer cells generate drug resistance to the medicine, the treatment effect of oxaliplatin is seriously affected, and gastrointestinal mucosa inflammation side effects such as nausea, vomiting and diarrhea are also often accompanied in the oxaliplatin administration process.
The soybean germ membrane has high protein content ratio, balanced amino acid types essential to human body, rich multiple nutrient elements such as various bioactive enzymes, soyasaponin, phytosterol, natural vitamin E and the like, and the contained soyasaponin is pentacyclic triterpene compound and has obvious proliferation inhibition and apoptosis induction effects on various tumor cells such as colon cancer cells, liver cancer cells, uterine cancer cells and the like, so that the soybean active peptide prepared by taking the soybean germ membrane as a raw material source has the advantages of high bioactivity, strong immunoregulation capability, rich amino acid nutrition, high human body safety and the like.
The combined application of the soybean active peptide and the oxaliplatin can effectively relieve CIPN adverse reaction caused by the administration of the oxaliplatin, relieve peripheral nerve injury symptoms such as mechanical allodynia, cold and hot hyperalgesia and the like, repair intestinal mucosa epithelial cell injury caused by chemotherapy drugs, relieve gastrointestinal mucosa inflammation such as nausea, vomiting and diarrhea and the like caused by the administration of the oxaliplatin, promote the growth inhibition and apoptosis induction effects of the oxaliplatin on liver cancer cells, enhance the sensitivity of liver cancer resistant cells to the oxaliplatin, improve secondary drug resistance conditions and promote the liver cancer treatment effect of the oxaliplatin.
At present, no literature or patent is reported and studied about the combined application of the soybean active peptide and the oxaliplatin in treating liver cancer, and the soybean active peptide has important clinical application significance in solving adverse reactions caused by the oxaliplatin and cell drug resistance.
Disclosure of Invention
Aiming at the existing clinical problems, the invention provides the application of the soybean active peptide in the liver cancer treatment process of oxaliplatin, and compared with monotherapy, the combined application of the soybean active peptide and oxaliplatin effectively reduces adverse reaction of the used medicines while improving the liver cancer treatment effect.
The soybean active peptide component and oxaliplatin are used together to effectively relieve peripheral injury symptoms such as mechanical allodynia, cold and hot hyperalgesia and the like, and simultaneously relieve adverse reactions of gastrointestinal mucosa inflammation medicines such as nausea, vomiting, diarrhea and the like.
Meanwhile, the proliferation inhibition and apoptosis induction effects of oxaliplatin on cancer cells are enhanced, and the occurrence of secondary drug resistance in the oxaliplatin administration process is reduced.
The soybean active peptide disclosed in the patent is prepared by processing soybean germ membrane as raw material, and the relative molecular weight of the active peptide is in the range of 400 daL-700 daL.
Further, the soy peptides of interest may be provided by the soy peptides alone or in any mixture containing the soy peptides, including but not limited to solid, gel and liquid formulations.
The solid preparation can contain one or more than one composition of starch, sucrose, dextrin, microcrystalline cellulose, lactose, pregelatinized starch, sodium carboxymethyl starch, crosslinked povidone, crosslinked sodium carboxymethyl cellulose, polyvinylpyrrolidone, cellulose derivatives, magnesium stearate and micro-powder silica gel besides the soybean active peptide component.
The liquid preparation may contain, in addition to the soybean active peptide component, one or more of water, ethanol, glycerin, propylene glycol, polyethylene glycol, fatty oil, liquid paraffin, sodium stearate, calcium stearate, oleic acid, sodium lauryl sulfate, sodium dodecylbenzenesulfonate, lecithin, soybean lecithin, sorbitan fatty acid, polysorbate, polyoxyethylene-polyoxypropylene copolymer, benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, benzalkonium bromide, and parahydroxybenzoate.
The gel can contain one or more than one composition of carbomer, polyethylene glycol, chitosan, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethylcellulose, triethanolamine, sodium hydroxide, ethylenediamine, laurylamine, sodium bicarbonate, glycerol, propylene glycol, ethanol, tween-80, sulfite, cysteine, di-tert-Butylhydroxytoluene (BHT) and potassium sorbate besides the soybean active peptide component.
Detailed Description
The present invention is specifically described by the following examples, which are provided for further illustration of the present invention and are not to be construed as limiting the scope of the present invention.
EXAMPLE 1 Soybean active peptide sensitivity influence experiment on oxaliplatin resistant cells
Human liver cancer HepG2 cells are purchased from Shanghai national center for sciences
Cell culture and experimental grouping
Establishing a cell drug resistance model
All cells were placed in RPMI1640 medium containing 10% calf serum at 37℃in 5% CO 2 Culturing in a saturated humidity incubator for 2-3 days for 1 time.
After completion of the cell culture, oxaliplatin at a concentration of 5. Mu.L and 20. Mu.g/mL was added to the cell culture solution at 1d, 7d, 14d and 21d, respectively, to establish a drug-resistant cell model.
Oxaliplatin resistant cells in the logarithmic growth phase were divided into 5 groups, which were respectively defined as a blank control group (oxaliplatin resistant cell group), oxaliplatin single drug group, oxaliplatin and soybean active peptide (high, medium, low dose) combined drug group.
Preparing 5×10 oxaliplatin-resistant cells in logarithmic growth phase into cell culture solution 4 Each of the cell suspensions was inoculated into a 96-well plate for culture. Oxaliplatin at a concentration of 20. Mu.L and 20. Mu.g/mL was added to the single drug group, and soybean active peptide at a concentration of 5. Mu.g/mL, 20. Mu.g/mL, and 50. Mu.g/mL were added to the combined drug group, respectively, and oxaliplatin at a concentration of 20. Mu.L and 20. Mu.g/mL was added to the blank group, respectively, and an equal volume of PBS solution was added.
Placing 5 groups of cells into a 37 ℃ incubator for culturing for 72 hours, respectively adding 20 mu L of MTT solution with the concentration of 5mg/mL, incubating for 4 hours, centrifuging for 10 minutes at 3600r/min, discarding supernatant, dissolving sediment with 200 mu L of DMSO, measuring absorbance values of each group at 570nm after full dissolution, and calculating the cell proliferation inhibition rate according to the absorbance values by the following formula.
SPSS software calculates cell ICs for each group 50 Values, drug resistance fold was calculated using the following formula:
fold drug resistance = oxaliplatin single drug group cell IC 50 Combination of soybean active peptide and group cell IC 50
Experimental results show that different doses of soybean active peptide respectively lead oxaliplatin to IC of drug-resistant cells 50 The values are reduced from 48.23+/-2.42 mug/mL to 25.08+/-1.56 mug/mL, 9.61+/-0.27 mug/mL and 5.09+/-1.43 mug/mL, so that the sensitivity of the drug-resistant cells to oxaliplatin is respectively improved by 1.92 times, 5.02 times and 9.49 times, and the experimental result shows that the soybean active peptide can effectively improve the drug sensitivity of the drug-resistant cells to oxaliplatin.
TABLE 1 Effect of Soybean active peptides on drug resistance of oxaliplatin resistant cells
Example 2 inhibition of proliferation and apoptosis effects of Soybean active peptide in combination with oxaliplatin on liver cancer cells
Hepatoma cell HepG2 was purchased from Shanghai department of science
Cell culture and experimental grouping
All cells were placed in RPMI1640 medium containing 10% calf serum at 37℃in 5% CO 2 Culturing in a saturated humidity incubator for 1-2 days for 1 time.
Taking human liver cancer HepG2 cell in logarithmic growth phase, digesting with 0.25% trypsin, and preparing into 5×10 4 Cell suspensions were inoculated in 96-well plates at 37℃and 5% CO 2 The culture was performed overnight in an incubator, and the culture solution was aspirated and discarded.
The treated HepG2 cells are divided into 5 groups, and the 5 groups are respectively a blank control group, an oxaliplatin single drug group and a high, medium and low dose combined drug group of oxaliplatin and soybean active peptide. Oxaliplatin at a concentration of 20. Mu.L and 20. Mu.g/mL was added to the single drug group, and soybean active peptide at a concentration of 5. Mu.g/mL, 20. Mu.g/mL, and 50. Mu.g/mL were added to the combined drug group, respectively, and oxaliplatin at a concentration of 20. Mu.L and 20. Mu.g/mL was added to the blank group, respectively, and an equal volume of PBS solution was added.
1. Experiment of influence of soybean active peptide combined with oxaliplatin on proliferation of human liver cancer HepG2 cells
MTT assay
After 5 groups of cells were put into a 37℃incubator and incubated for 24 hours, 48 hours and 72 hours, 20. Mu.L of MTT solution with a concentration of 5mg/mL was added, after 6 hours of incubation, the solution was centrifuged for 10 minutes at 4500r/min, the supernatant was discarded, the precipitate was dissolved in 200. Mu.L of DMSO, after complete dissolution, the absorbance value of each group of bacterial suspensions was measured at 490nm, and the cell proliferation inhibition rate was calculated according to the absorbance value as shown in the following formula.
Cell proliferation inhibition (%) = (1-experimental group value/blank control group absorbance value) ×100%
2. Experiment of influence of soybean active peptide combined with oxaliplatin on apoptosis of human liver cancer HepG2 cells
Annexin V-FITC method detection
Culturing 5 groups of cells in an incubator at 37 ℃ for 24 hours, collecting the cells, digesting the cells by 0.25% trypsin, transferring the cells into an EP tube,centrifuging (2000 r/min,15 min), discarding supernatant, washing with PBS 3 times at 4deg.C, and adjusting its density to 5×10 6 After 5. Mu.L of Annexin V reagent was added to each of the cells/mL, the cells were allowed to react at room temperature for 30min in the dark, and apoptosis was detected on a flow cytometer.
Experiment results show that compared with an oxaliplatin single-drug group, the proliferation inhibition effect of the soybean active peptide high-dose combined-drug group, the soybean active peptide medium-dose combined-drug group and the soybean active peptide low-dose combined-drug group on HepG2 cells is obviously enhanced in 72 hours after administration, wherein the proliferation inhibition rate of the soybean active peptide high-dose combined-drug group on the HepG2 cells in 24 hours, 48 hours and 72 hours respectively reaches 51.66+/-3.74%, 79.03 +/-2.64% and 85.56 +/-4.24%; in the experiment of influence on HepG2 apoptosis, compared with a single drug group, the apoptosis rate of the soybean active peptide combined drug group for 24 hours is obviously increased, and the apoptosis rates of high, medium and low dose groups are respectively 53.12+/-3.67%, 57.42+/-2.59% and 61.75 +/-1.02%, which are shown as dose correlation. Experimental results show that the soybean active peptide and oxaliplatin can be used in combination to effectively enhance the growth inhibition and apoptosis promotion effects of the soybean active peptide and oxaliplatin on liver cancer cells, and improve the treatment effect of the soybean active peptide and oxaliplatin.
TABLE 2 Effect of Soybean active peptides on HepG2 cell proliferation inhibition Rate
TABLE 3 Effect of Soybean active peptides on apoptosis of HepG2 cells
Example 3 experiments on the Effect of Soybean active peptide on oxaliplatin-induced diarrhea
Grouping and administration
The method comprises the steps of selecting 48 SD rats, randomly dividing the SD rats into 6 groups, namely a blank control group, a model group, a positive control pefeikang group and high, medium and low dosage groups of soybean active peptide, wherein 8 SD rats are selected from each group.
Establishment of rat diarrhea model
Except for the blank groups, oxaliplatin is injected into abdominal cavity for 20mg/kg, and is continuously injected for 7d, so that an animal model of intestinal mucositis is established, and the blank groups are given with equal volume of physiological saline.
After the molding is completed, the positive control group is filled with the pefikang solution with the dosage of 20mg/kg every day, the high, medium and low dosage groups of the soybean active peptide are respectively filled with the soybean active peptide with the dosages of 180mg/kg, 120mg/kg and 60mg/kg every day, and the blank control group and the model group are filled with the physiological saline with the same volume for 1 time every day and are continuously filled with the stomach for 14 days.
Investigation of diarrhea Condition in rats
The number of loose stools (based on the presence or absence of stains on the filter paper) of the rats was observed and recorded at 7d and 14d after the administration, and the corresponding loose stool grades of the rats were calculated
The stool grade is divided into 4 grades, 1 grade, the stain diameter is smaller than 1cm, 2 grade, the stain diameter is 1-1.9 cm, 3 grade, the stain diameter is 2-3 cm, 4 grade, and the stain diameter is larger than 3cm according to the size of the stain range on the filter paper.
The experimental results showed that the rats in the remaining groups all exhibited different diarrhea symptoms compared to the blank group. Compared with a model group, the number of loose stool and the loose stool grade of rats in the groups of high, medium and low doses of the 7d and 14d synchronous soybean active peptides are obviously reduced, the number of loose stool and the loose stool grade of the high dose groups of 7d and 14d are respectively 6.07+/-1.46, 2.47+/-0.18 and 5.01+/-1.52, and 1.95+/-0.30, and diarrhea symptoms are improved, so that the result shows that the soybean active peptides can effectively relieve diarrhea symptoms caused by oxaliplatin.
TABLE 4 Effect of Soybean active peptides on diarrhea status in rats
Example 4 experiments on the effects of Soybean active peptide on oxaliplatin-induced nausea and vomiting in mice
Grouping and administration
60 Kunming mice were randomly divided into 6 groups, which were respectively set as a normal control group, a model group, a positive control ondansetron group, and a soybean active peptide low, medium, and high dose group, each group having 10 animals. Positive control ondansetron mice were intraperitoneally injected with ondansetron hydrochloride injection 5mL/kg, and soybean active peptide in high, medium and low dose groups were respectively infused with 180mg/kg, 120mg/kg and 60mg/kg soybean active peptide daily, and the blank control group and model group were given the same volume of physiological saline to be infused with stomach 1 time daily for 7 days.
After the last gastric lavage for 2 hours, oxaliplatin was diluted with physiological saline to an injection of 0.5mg/mL, and tail vein injection was performed on the mice of each of the remaining groups except the blank group at a dose of 9 mL/kg.
After oxaliplatin injection is completed, the number of retching and vomiting of the mice in 0-24 h, 24-48 h and 48-72 h is observed.
Experimental results show that compared with a blank control group, the retching times of mice in the model group are obviously increased; compared with a model group, the retching times of the mice in the high, medium and low dosage groups of the soybean active peptide are obviously reduced in each period, the effect of reducing the soybean active peptide in the high dosage group is most obvious, and the retching times of the mice in the high dosage groups of 24h, 48h and 72h are 54.64 +/-13.78 times, 33.01 +/-12.53 times and 26.27+/-12.54 times respectively, and are reduced by 119.59 times, 106.52 times and 89.45 times respectively compared with the model group in the same period. Experimental results show that the soybean active peptide can effectively relieve nausea and retching symptoms of mice caused by oxaliplatin administration, and effectively reduce vomiting times.
Table 5 number of retching times in mice of each group
| Group of | dosage/mL kg -1 | 0～24 | 24～48 | 48～72h |
| Blank control group | 0 | 0 | 0 | |
| Model group | 174.23±22.06 | 139.53±13.95 | 115.72±18.52 | |
| Ondansetron group | 5 | 77.24±15.21 | 52.64±11.66 | 45.22±13.63 |
| Soybean active peptide low dose group | 60 | 73.26±14.64 | 47.72±13.05 | 39.63±15.56 |
| Soybean active peptide medium dose group | 120 | 66.75±12.22 | 41.63±15.18 | 32.51±14.32 |
| Soybean active peptide high dose group | 180 | 54.64±13.78 | 33.01±12.53 | 26.27±12.54 |
EXAMPLE 5 Effect of Soybean active peptide on peripheral nerve injury in rats caused by oxaliplatin administration
Experimental grouping and administration
72 SD rats were selected and randomly divided into 6 groups, namely a blank control group, a model group, a positive control reduced glutathione group and high, medium and low doses of soybean active peptide, each group comprising 12 soybean active peptides.
Except for a blank group, rats in each group are intraperitoneally injected with 20mg/kg oxaliplatin every other day, and a peripheral nerve injury model of the rats caused by oxaliplatin is built for 7 days, and rats in a blank control group are intraperitoneally injected with physiological saline with the same volume.
After the molding is completed, the positive control group is filled with 15mg/kg of reducing glutathione solution every day, the high, medium and low doses of soybean active peptide are respectively filled with 180mg/kg, 120mg/kg and 60mg/kg of soybean active peptide every day, and the blank control group and the model group are respectively filled with physiological saline with the same volume for 1 time every day and continuously filled with the stomach for 21 days.
Peripheral nerve injury rat behavioural detection
The rats were subjected to mechanical hyperalgesia, hypersensitivity tests and cold stimulus sensitivity tests at 1, 7, 14 and 21d of administration, respectively, to evaluate the peripheral nerve injury of the rats in terms of hyperalgesia and hyperalgesia, cold stimulus induced footage.
(1) Mechanical hyperalgesia, hypersensitivity test
A (30X 15 cm) transparent glass box is placed on an iron wire net, after a rat adapts for 5min, vonFrey fiber filaments with a folding force of 4g and 15g are respectively taken to vertically stimulate the midfoot of the hindlimb of the rat, each foot is measured 5 times, the time interval between each stimulation is longer than 6s, the rapid foot lifting reaction of the rat is recorded as positive reaction in the stimulation time or immediately when the fiber is removed, and the reaction times of two hindfeet of each rat to the 4g and 15g pain measuring filaments and the percentage of the total stimulation times are respectively taken as the degree of mechanical abnormal pain of the rat.
The lifting reaction of the rat sole is stimulated by 4g of VonFrey fiber to be mechanical stimulation pain hypersensitivity reaction, namely animal reaction can be caused by slight stimulation, and the lifting reaction of the rat sole is stimulated by 15g of VonFrey fiber to be mechanical stimulation hyperalgesia reaction.
(2) Cold stimulus sensitivity test
Cold pain in rats was induced by acetone and the number of foot contractions was recorded.
The rats are placed on a metal net and covered with a transparent plastic cover, after the rats adapt to the rats for 5min, 50 mu L of acetone is sprayed on the centers of the hind limb soles of the rats each time, and the number of times of foot shrinkage and foot licking in the rats for 60s is recorded.
The experimental results show that under the stimulation conditions of 4g and 15g of VonFrey fiber, compared with a blank group, the model group and rats of each administration group have increased foot shrinkage percentage, and the mechanical hyperalgesia and hypersensitive symptoms are obvious; with the advancement of the administration process, the foot shrinking proportion of the soybean active peptide high, medium and low dose groups of rats is obviously reduced compared with that of the model group from 7d, and the foot shrinking percentages of the soybean active peptide high dose groups of 7d, 14d and 21d of VonFrey4g are respectively 16.34+/-1.44%, 28.30+/-1.37% and 33.49+/-3.83%; the percentage of VonFrey15g foot shrinkage is 27.02+/-2.75%, 31.63+/-1.72% and 39.27+/-2.02%, respectively, and the mechanical hyperalgesia and hypersensitive symptoms of the rats are obviously improved. Compared with a model group, the cold-stimulus foot-shrinking test result of the rat shows that the foot-shrinking times of rats of each administration group of the soybean active peptide are obviously reduced in the same period, the high-dose group of the soybean active peptide has the most obvious effect, the foot-shrinking times of 7d, 14d and 21d are respectively 3.85+/-1.89 times, 5.52+/-1.07 times and 7.60+/-2.29 times, and the cold-pain stimulus symptoms of the rat are reduced. Experimental results show that the soybean active peptide can effectively relieve peripheral nerve injury symptoms caused by oxaliplatin administration and relieve adverse reactions of pain abnormality.
TABLE 6 VonFrey4g footshrink percentage%
| Group of | Dosage/mg.kg -1 | 0d | 7d | 14d | 21d |
| Blank control group | —— | 2.48±1.30 | 2.73±2.14 | 3.25±1.76 | 3.57±1.43 |
| Model group | —— | 13.27±1.14 | 44.40±2.53 | 69.36±1.11 | 83.32±3.53 |
| Positive control group | 20mg／kg | 12.93±2.09 | 28.53±1.42 | 37.55±2.36 | 46.24±1.82 |
| Soybean active peptide low dose group | 3mg/kg | 12.25±2.46 | 25.78±2.45 | 35.12±1.08 | 42.93±2.50 |
| Soybean active peptide medium dose group | 9mg/kg | 12.04±1.92 | 21.53±1.37 | 32.29±3.39 | 38.37±1.57 |
| Soybean active peptide high dose group | 18mg/kg | 11.36±2.57 | 16.34±1.44 | 28.30±1.37 | 33.49±3.83 |
TABLE 7 VonFrey15g footage percentage%
| Group of | Dosage/mg.kg -1 | 0d | 7d | 14d | 21d |
| Blank control group | —— | 22.64±2.51 | 23.16±1.08 | 23.53±2.55 | 25.78±1.92 |
| Model group | —— | 35.57±3.63 | 64.65±2.23 | 79.16±2.44 | 90.52±1.66 |
| Positive control group | 20mg／kg | 29.04±1.42 | 37.43±2.46 | 42.74±3.75 | 53.06±4.48 |
| Soybean active peptide low dose group | 3mg/kg | 27.56±3.18 | 33.94±4.02 | 39.09±4.48 | 49.47±2.83 |
| Soybean active peptide medium dose group | 9mg/kg | 26.74±2.03 | 31.53±2.54 | 37.51±2.40 | 46.04±3.45 |
| Soybean active peptide high dose group | 18mg/kg | 24.91±2.20 | 27.02±2.75 | 31.63±1.72 | 39.27±2.02 |
Table 8 cold stimulation number of foot contractions/time in rats
| Group of | Dosage/mg.kg -1 | 0d | 7d | 14d | 21d |
| Blank control group | —— | 1.53±0.30 | 1.74±0.28 | 2.02±1.03 | 2.42±0.97 |
| Model group | —— | 2.53±1.62 | 5.61±1.14 | 9.06±2.28 | 12.59±2.04 |
| Positive control group | 20mg／kg | 2.41±2.75 | 4.86±1.74 | 7.74±1.36 | 10.33±3.64 |
| Soybean active peptide low dose group | 3mg/kg | 2.23±1.73 | 4.51±1.02 | 6.53±2.48 | 9.84±2.70 |
| Soybean active peptide medium dose group | 9mg/kg | 2.02±1.18 | 4.24±2.63 | 6.21±3.61 | 9.27±1.45 |
| Soybean active peptide high dose group | 18mg/kg | 1.99±0.72 | 3.85±1.89 | 5.52±1.07 | 7.60±2.29 |
Claims (6)
1. The application of the soybean active peptide in the liver cancer treatment process of oxaliplatin is characterized in that the soybean active peptide can enhance the proliferation inhibition and apoptosis induction effects of oxaliplatin on cancer cells, reduce the secondary drug resistance condition in the oxaliplatin administration process, reduce the peripheral neuropathy (CIPN) symptoms caused by administration, and relieve the adverse drug reactions related to gastrointestinal mucosal inflammation such as nausea, vomiting, diarrhea and the like.
2. The use of the soybean active peptide in the liver cancer treatment process of oxaliplatin according to claim 1, wherein the soybean active peptide is prepared by processing soybean germ membrane as raw material, and the relative molecular weight of the active peptide is in the range of 400 daL-700 daL.
3. The use of the soybean active peptide according to claim 1, wherein the soybean active peptide is provided by the soybean active peptide alone or in any mixture containing the soybean active peptide component, wherein the mixture comprises but is not limited to solid preparation, gel preparation and liquid preparation.
4. The solid preparation according to claim 3, wherein the solid preparation contains one or more of starch, sucrose, dextrin, microcrystalline cellulose, lactose, pregelatinized starch, sodium carboxymethyl starch, crospovidone, croscarmellose sodium, polyvinylpyrrolidone, cellulose derivative, magnesium stearate, and colloidal silicon dioxide in addition to the soybean active peptide component.
5. A liquid formulation according to claim 3, characterized in that: besides the soybean active peptide component, the composition can also contain one or more than one of water, ethanol, glycerol, propylene glycol, polyethylene glycol, fatty oil, liquid paraffin, sodium stearate, calcium stearate, oleic acid, sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, lecithin, soybean lecithin, fatty acid sorbitan, polysorbate, polyoxyethylene-polyoxypropylene copolymer, benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, benzalkonium bromide and parahydroxybenzoate.
6. A gel according to claim 3, characterized in that: in addition to the soybean active peptide component, the soybean active peptide component can also contain one or more than one of carbomer, polyethylene glycol, chitosan, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethylcellulose, triethanolamine, sodium hydroxide, ethylenediamine, laurylamine, sodium bicarbonate, glycerol, propylene glycol, ethanol, tween-80, sulfite, cysteine, di-tert-Butylhydroxytoluene (BHT) and potassium sorbate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111405911.9A CN116159122A (en) | 2021-11-24 | 2021-11-24 | Application of soybean active peptide in liver cancer treatment process of oxaliplatin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111405911.9A CN116159122A (en) | 2021-11-24 | 2021-11-24 | Application of soybean active peptide in liver cancer treatment process of oxaliplatin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116159122A true CN116159122A (en) | 2023-05-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111405911.9A Pending CN116159122A (en) | 2021-11-24 | 2021-11-24 | Application of soybean active peptide in liver cancer treatment process of oxaliplatin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116159122A (en) |
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2021
- 2021-11-24 CN CN202111405911.9A patent/CN116159122A/en active Pending
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