CN113694185A - Application of bioactive peptide in preparation of medicine for preventing and treating anthracycline cardiotoxicity - Google Patents
Application of bioactive peptide in preparation of medicine for preventing and treating anthracycline cardiotoxicity Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines for preventing and treating cardiotoxicity, and particularly relates to application of bioactive peptide in preparation of medicines for preventing and treating anthracycline cardiotoxicity. The bioactive peptide is albumin peptide, wheat oligopeptide, soybean peptide or corn oligopeptide, and the anthracycline drug is adriamycin or daunorubicin. The invention discovers biological functions of albumin peptide, wheat oligopeptide, soybean peptide and corn oligopeptide except oxidation resistance and tumor resistance, and expands the application range of the bioactive peptide; the bioactive peptide has obvious effect on preventing and treating anthracycline cardiotoxicity and has no side effect.
Description
Technical Field
The invention relates to the technical field of medicines for preventing and treating cardiotoxicity, in particular to application of bioactive peptide in preparing medicines for preventing and treating anthracycline cardiotoxicity.
Background
Anthracyclines refer to a class of chemotherapeutic drugs containing anthracyclines, including doxorubicin (doxorubicin), epirubicin (epirubicin), doxorubicin, daunorubicin, doxorubicin, idarubicin, and the like. The medicine is clinically used for treating malignant tumors and solid tumors of a blood system, including acute leukemia, lymphoma, breast cancer, ovarian cancer, gastric cancer, soft tissue sarcoma and the like for half a century, is a medicine with milestone significance, and is still a basic medicine for treating a plurality of malignant tumors and solid tumors of the blood system due to the characteristics of wide anti-tumor effect, good curative effect and the like even though new therapies such as targeted therapy, immunotherapy and the like are continuously emerged at present. However, adverse reactions such as cardiotoxicity generated by the medicines seriously affect the clinical application of the medicines, so the medicines still have the problem to be solved urgently at present.
Aiming at the cardiotoxicity of anthracycline drugs, the currently approved cardiotoxicity protective agent dexrazoxane can obtain certain clinical curative effect in short-term application, but has great uncertainty in the aspects of long-term curative effect and prevention of long-term cardiotoxicity adverse events. In addition, dexrazoxane can only be injected and administered, the price is high, and the adverse reaction is not negligible. Therefore, the search for safe and effective anthracycline drug protective agents has important clinical application value.
Bioactive peptides (Bioactive peptides) are peptide substances which are derived from natural products and have certain bioactivity, and have bioactivity of resisting oxidation, resisting tumor, improving immunity and the like.
Disclosure of Invention
The dexrazoxane serving as the cardiotoxicity protective agent of the prior anthracycline can only be injected, has high price and serious adverse reaction, and provides a new function of bioactive peptide for solving the problem of lack of a safe and effective anthracycline protective agent at present, which is particularly shown in the application of preparing the cardiotoxicity protective agent of the anthracycline.
The technical scheme of the invention is as follows:
the invention provides application of bioactive peptide in preparing medicine for preventing and treating anthracycline cardiotoxicity.
Further, the bioactive peptide is albumin peptide, wheat oligopeptide, soybean peptide or corn oligopeptide.
Further, the anthracycline is adriamycin or daunorubicin.
Furthermore, the anthracycline cardiotoxicity prevention and treatment drug is a drug for preventing and treating decrease of left ventricular ejection fraction and/or left ventricular short axis shortening rate caused by anthracycline drugs.
Furthermore, the medicine for preventing and treating anthracycline cardiotoxicity is a medicine for preventing and treating increase of serum lactate dehydrogenase activity and/or reduction of serum glutathione content caused by anthracycline medicines.
Furthermore, the medicine for preventing and treating anthracycline cardiotoxicity is a medicine for preventing and treating myocardial superoxide dismutase activity reduction and/or cardiac malondialdehyde content increase caused by anthracycline medicines.
The invention has the beneficial effects that: the bioactive peptide is derived from natural products, has high safety, easy absorption, wide sources and low price, and has obvious antioxidant activity, immune function regulation and the like, thus becoming a research hotspot. Aiming at toxic and side effects in the treatment process of anthracycline antitumor drugs, no ideal prevention and treatment method exists at present. According to the invention, the first research shows that the bioactive peptide has an obvious inhibiting effect on cardiotoxicity caused by anthracyclines, the bioactive peptide can improve the survival rate of mice, and the application range of albumin peptide, wheat oligopeptide, soybean peptide and corn oligopeptide is expanded; the bioactive peptide has obvious effect on preventing and treating anthracycline cardiotoxicity and has no side effect.
Drawings
FIG. 1 is a graph of the results of the effect of four biologically active peptides of the invention on LVEF in doxorubicin mice;
FIG. 2 is a graph showing the results of the effect of four bioactive peptides of the present invention on LVFS of doxorubicin mice;
FIG. 3 is a graph of the results of the effect of four biologically active peptides of the invention on LDH in doxorubicin mice;
FIG. 4 is a graph of the results of the effect of four bioactive peptides of the present invention on doxorubicin mouse GSH;
FIG. 5 is a graph of the results of the effect of four biologically active peptides of the present invention on doxorubicin mouse SOD;
FIG. 6 is a graph of the results of the effect of the bioactive peptides of the present invention on Adriamycin mouse MDA;
FIG. 7 is a graph of myocardial histopathology results of the present invention (× 200);
FIG. 8 is a graph showing the results of the effect of the bioactive peptides of the present invention on LVEF of daunorubicin mice;
FIG. 9 is a graph showing the results of the effect of the bioactive peptides of the present invention on LVFS of daunorubicin mice;
FIG. 10 is a graph of the results of the effect of the bioactive peptides of the present invention on LDH in daunorubicin mice;
FIG. 11 is a graph of the results of the effect of the bioactive peptides of the present invention on daunorubicin mouse GSH;
FIG. 12 is a graph showing the results of the effect of the bioactive peptides of the present invention on daunorubicin mouse SOD;
FIG. 13 is a graph showing the results of the effect of the bioactive peptides of the present invention on daunorubicin mouse MDA;
FIG. 14 is a graph of myocardial histopathology results of the present invention (× 200);
in all the above figures, as compared with the normal control group P<0.01; in comparison with model group, # P<0.05，## P<0.01。
Detailed Description
The present invention will be described in more detail with reference to the following embodiments for understanding the technical solutions of the present invention, but the present invention is not limited to the scope of the present invention.
The invention provides application of bioactive peptide in preparing medicine for preventing and treating cardiotoxicity of anthracycline.
As an embodiment, the bioactive peptide is albumin peptide, wheat oligopeptide, soybean peptide or corn oligopeptide.
As an embodiment, the anthracycline is doxorubicin or daunorubicin.
As an embodiment, the anthracycline cardiotoxic drug is a drug for preventing decrease of left ventricular ejection fraction and/or left ventricular short axis shortening rate caused by anthracycline.
In one embodiment, the anthracycline cardiotoxicity prevention and treatment drug is a drug for preventing and treating increase of serum lactate dehydrogenase activity and/or decrease of serum glutathione content caused by anthracycline drugs.
As an implementation mode, the anthracycline cardiotoxicity prevention and treatment drug is a drug for preventing and treating decrease of serum glutathione content, and/or decrease of myocardial superoxide dismutase activity, and/or increase of cardiac malondialdehyde content caused by anthracycline drugs.
The albumin peptide (production lot: 20181072502), the wheat oligopeptide (production lot: 2018081402) and the corn oligopeptide (production lot: 20180801027) used in the present invention were purchased from Zhongshi Duoqing (Shandong) Biotechnology Co., Ltd., soybean peptide: purchased from shansong bioproduct limited (shandong), production lot number: 20181030.
first, the influence of bioactive peptide on the survival rate of adriamycin (DOX for short) mice
1. Laboratory animal
6-8 week-old SPF grade C57BL/6 male mice were purchased from the Henan province laboratory animal center (production permit: SCXK 2017-. After 5 days of adaptive feeding and observation, healthy and active mice were selected for experiments.
2. Grouping and administration of drugs
The 60C 57BL/6 mice were randomly divided into 6 groups, a: the normal control group was injected intraperitoneally with a normal saline solution at a dose of 17 mg/kg every day. After 30 min, distilled water was administered at a dose of 600mg/kg by gavage 1 time every other day. B: DOX group, 17 mg/kg daily dose of DOX was injected intraperitoneally. After 30 min, distilled water was administered at a dose of 600mg/kg by gavage 1 time every other day. C: DOX + Albumin peptide group, 17 mg/kg dose DOX was injected intraperitoneally daily. After 30 min, the albumin peptide was gavaged at a dose of 600mg/kg 1 time every other day. D: DOX + wheat oligopeptide group, which was injected intraperitoneally at a dose of 17 mg/kg per day. After 30 min, the wheat oligopeptide is administrated by stomach irrigation at the dose of 600mg/kg, and 1 time every other day. E: DOX + Soy peptide group, 17 mg/kg dose DOX was injected intraperitoneally daily. After 30 min, the soybean peptide was administered 1 time every other day at a dose of 600mg/kg by gavage. F: DOX + corn oligopeptide group, injected intraperitoneally with DOX at a dose of 17 mg/kg daily. The corn oligopeptide is administered by gavage at a dose of 600mg/kg after 30 min, 1 time every other day. The above treatment was continued for 7 days.
3. Survival rate observation
Mice survival was observed and recorded daily.
4. Results
As shown in table 1, mice in the DOX group began to die by day 5. After 7 days, the survival rate of the mice in the normal control group is 100%, the survival rate of the mice in the DOX group is only 30%, the survival rate of the DOX + albumin peptide group is 50%, the survival rate of the DOX + wheat oligopeptide group is 40%, the survival rate of the DOX + soybean peptide group is 50%, and the survival rate of the DOX + corn oligopeptide group is 40%, which indicates that the survival rates of the mice in all bioactive peptides can be improved.
Table 1 daily survival rate (%)
Second, the influence of bioactive peptide on the toxic and side effects of adriamycin
1. Grouping and administration of drugs
The experimental animals and the grouping and administration method in the above-mentioned "influence of bioactive peptide on the survival rate of Doxorubicin (DOX) mice" were adopted, but the unit number was 6 per group, and the observation time was 4 days.
2. Mouse cardiac function detection
On the 4 th day of the experiment, a proper amount of depilatory cream is uniformly smeared on the heart part by using a cotton swab, and the skin of the heart part is completely exposed by carefully wiping the heart part with a wet tissue for depilation. Injecting chloral hydrate into abdominal cavity at a dose of 0.04 mL/10g (or 400 mg/kg), fixing on the operation board with chest facing upwards after 5 min, and uniformly smearing proper amount of special coupling agent for detection on heart. And then placing a matched probe of the Vevo 2100 high-resolution small animal ultrasonic imaging system on the chest of the mouse, observing the images, adjusting the proper position, observing the long-axis section of the sternum through B-type ultrasonic, storing the images, switching to M-type ultrasonic, and storing the image at the position with the maximum diameter of the lower left ventricle. Left Ventricular Ejection Fraction (LVEF) and Left Ventricular short axis Shortening (LVFS) are obtained by processing with equipment-owned software.
As a result: as shown in FIGS. 1 and 2, LVEF and LVFS were significantly reduced in both DOX mice as compared to the normal control group (L) ((L))PAll values are less than 0.01). Compared with the DOX group, the cardiac function of 4 groups of mice given 4 bioactive peptides is obviously improved.
3. Detection of LDH activity and GSH content in mouse serum
On day 4 of the experiment, each group of mice was bled from the eye and serum was centrifuged to detect Lactate Dehydrogenase (LDH) and Glutathione (GSH).
As a result: as shown in FIG. 3, the LDH activity in the serum of the mice in the DOX group is significantly increased compared with that in the normal control group (P<0.01). Compared with the DOX group, the LDH activity of 4 groups of mice administrated with bioactive peptide by gavage is obviously reduced (PAll values are less than 0.01).
As shown in FIG. 4, the serum GSH content of the mice in the DOX group is significantly reduced compared with that in the normal control group (P<0.01); compared with the DOX group, the serum GSH content of 4 groups of mice which are administrated with 4 kinds of bioactive peptides by intragastric administration is obviously increased, wherein the DOX + albumin peptide group is increased most obviously.
4. Mouse myocardial SOD activity and heart MDA content detection
Separating mouse heart, weighing 0.07 g heart, placing in 630 μ L physiological saline, preparing tissue homogenate with ULTRA-TURRAX high speed homogenizer, centrifuging at 4 deg.C and 2000 rpm for 15 min, collecting supernatant, and detecting Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) content.
As a result: as shown in fig. 5, myocardial SOD activity was significantly decreased in mice in DOX group compared to normal control group (P < 0.01); compared with the DOX group, the heart SOD activity of 4 groups of mice which are administrated with 4 kinds of bioactive peptides by intragastric administration is obviously improved.
As shown in fig. 6, heart MDA content of mice in DOX group was significantly increased (P < 0.01) compared to normal control group; compared with the DOX group, the heart MDA content of 4 groups of mice which are administrated with 4 kinds of bioactive peptides by intragastric administration is obviously reduced, wherein the DOX + soybean peptide group is most obviously reduced.
5. Morphological observation of myocardial tissue
On the 4 th day of the experiment, 1/4 myocardial tissues of the apex of the left ventricle of the heart of the mouse were taken, fixed with 10% paraformaldehyde solution, dehydrated, cleared, embedded, sectioned and stained with hematoxylin-eosin (H-E). The morphology of the myocardial tissue is observed under a light microscope, photographed and contrasted for analysis.
As a result: FIG. 7 is the results of HE staining of heart tissue in various groups of mice, and it can be seen that: the normal control group (A) mice had well-arranged myocardial tissues and a complete structure. The myocardial fibers of the mice in the DOX group (B) are broken, disorderly arranged and even disappear, and the myocardial interstitium has inflammatory reaction. Mouse myocardial tissues of DOX + albumin peptide group (C), DOX + wheat oligopeptide group (D), DOX + soybean peptide group (E) and DOX + corn oligopeptide group (F) are similar to DOX, and myocardial fiber breakage, arrangement disorder, inflammation and the like occur.
Effect of bioactive peptides on survival of Daunorubicin (DNR) mice
1. Laboratory animal
6-8 week-old SPF grade C57BL/6 male mice were purchased from the Henan province laboratory animal center (production permit: SCXK 2017-. After 5 days of adaptive feeding and observation, healthy and active mice were selected for experiments.
2. Grouping and administration of drugs
Randomly dividing 60 SPF (specific pathogen free) grade C57BL/60 mice with the weight of 18-20 g into 6 groups, A: normal control group was injected intraperitoneally with normal saline at a dose of 11 mg/kg daily. After 30 min, distilled water was administered at a dose of 600mg/kg by gavage 1 time every other day. B: DNR group, 11 mg/kg daily dose of intraperitoneal DNR. After 30 min, distilled water was administered at a dose of 600mg/kg by gavage 1 time every other day. C: DNR + Albumin peptide group, 11 mg/kg dose of DNR was injected intraperitoneally daily. After 30 min, the albumin peptide was gavaged at a dose of 600mg/kg 1 time every other day. D: DNR + wheat oligopeptide group, 11 mg/kg dose of DNR was injected intraperitoneally daily. After 30 min, the wheat oligopeptide is administrated by stomach irrigation at the dose of 600mg/kg, and 1 time every other day. E: DNR + Soy peptide group, 11 mg/kg dose of DNR was injected intraperitoneally daily. After 30 min, the soybean peptide was administered 1 time every other day at a dose of 600mg/kg by gavage. F: the DNR + maize oligopeptide group was injected intraperitoneally with DNR at a dose of 11 mg/kg daily. The corn oligopeptide is administered by gavage at a dose of 600mg/kg after 30 min, 1 time every other day. The above treatment was continued for 7 days.
3. Survival rate observation
Mice were observed daily for survival.
4. Results
As shown in table 2, the survival rate of the DNR group mice was 80% from day 5. After 7 days of observation, the survival rate of the mice in the normal control group is 100%, while the survival rate of the mice in the DNR group is only 20%, the survival rate of the DNR + albumin peptide group is 50%, the survival rate of the DNR + wheat oligopeptide group is 40%, the survival rate of the DNR + soybean peptide group is 40%, and the survival rate of the DNR + corn oligopeptide group is 30%, which indicates that the survival rates of the mice can be improved by the 4 soybean bioactive peptides.
TABLE 2 Effect of bioactive peptides on survival of daunorubicin mice (%)
Research on protection effect of bioactive peptide on toxicity caused by daunorubicin
1. Laboratory animal
6-8 weeks old healthy C57BL/6 male mice were purchased from the center of laboratory animals (production permit: SCXK 2017-. After 5 days of acclimatization and observation, healthy mice were selected for the experiment.
2. Grouping and administration of drugs
36C 57BL/6 mice weighing 18-22g were randomly divided into 6 groups, A: normal control group, B: DNR group, C DNR + albumin peptide group, D DNR + wheat oligopeptide group, E.DNR + soybean oligopeptide group and F.DNR + corn oligopeptide group. B. C, D, E, F five groups were injected with 1mg/kg dose of intraperitoneal DNR, and group A was injected with the same amount of saline. After 1 hour, C, D, E, F four groups were intragastrically administered with albumin peptide, wheat oligopeptide, soybean oligopeptide, corn oligopeptide at a dose of 600mg/kg (0.2ml/10g), and A, B two groups of intragastrically equivalent physiological saline. The preparation is administered every other day for 4 consecutive days, 2 times. The general condition of each group of mice was observed daily.
3. Detection of cardiac function in mice
On the 4 th day of the experiment, a proper amount of depilatory cream is uniformly smeared on the heart part by using a cotton swab, and the skin of the heart part is completely exposed by carefully wiping the heart part with a wet tissue for depilation. Injecting chloral hydrate into the abdominal cavity at a dose of 0.04 mL/10g (or 400 mg/kg), opening the main machine of the ultrasonic instrument, taking out the probe (MS-400) of the small animal ultrasonic instrument, anesthetizing the mouse after installation, placing the mouse with the chest facing upwards on an operation panel, holding the probe by hand, enabling the incisal side of the probe to face the head of the animal, finely adjusting to rotate 30-45 degrees anticlockwise, searching the parasternal long axis section of the heart through a B-mode picture, and switching to an M-mode interface to record the image of the maximum diameter part of the left ventricle. The Ejection Fraction (EF), left ventricular minor axis shortening rate (FS), left ventricular end-systolic internal diameter (LVEDD) and left ventricular end-diastolic internal diameter (LVEDD) of the mice were recorded according to the instrumentation with data processing software.
As a result: as shown in fig. 8 and 9, both LVEF and LVFS were significantly reduced in the DNR group mice compared to the normal control group (P values were less than 0.01). Both LVEF and LVFS were significantly improved in the 4 groups of mice given bioactive peptides compared to the DNR group.
4. Detection of LDH activity and GSH content in mouse serum
On the 4 th day of the experiment, blood is taken from the eyeballs of the mice of each group, and serum is taken by centrifugation to detect LDH and GSH.
As a result: as shown in fig. 10: compared with a normal control group, the serum LDH activity of the mice in the DNR group is obviously increased (P < 0.01). Compared with the DNR group, the LDH activity of serum of 4 groups of mice given 4 bioactive peptides is remarkably reduced (P values are all less than 0.05).
5. Detection of myocardial SOD activity and myocardial MDA content in mice
Separating mouse heart, weighing 0.07 g heart, placing in 630 μ L physiological saline, preparing tissue homogenate with ULTRA-TURRAX high speed homogenizer, centrifuging at 4 deg.C and 2000 rpm for 15 min, and collecting supernatant for detecting SOD and MDA.
As a result: as shown in fig. 11, serum GSH levels were significantly reduced in DNR mice compared to normal controls (P < 0.01); compared with DNR group, 4 groups of mice administrated with bioactive peptide by gavage have obviously raised serum GSH content.
As shown in fig. 12, myocardial SOD activity was significantly decreased in DNR group mice compared to normal control group (P < 0.01); compared with DNR group, the myocardial SOD activity of 4 groups of mice given the bioactive peptide is obviously increased.
As shown in fig. 13, cardiac MDA content was significantly increased in mice in DNR group compared to normal control group (P < 0.01); compared with DNR group, the heart MDA content of 4 groups of mice administrated with bioactive peptide by gavage is obviously reduced.
6. Morphological observation of myocardial tissue
On the 4 th day of the experiment, 1/4 myocardial tissues of the apex of the left ventricle of the heart of the mouse were taken, fixed with 10% paraformaldehyde solution, dehydrated, cleared, embedded, sectioned and stained with hematoxylin-eosin (H-E). The morphology of the myocardial tissue is observed under a light microscope, photographed and contrasted for analysis.
As a result: FIG. 14 is the results of HE staining of heart tissue in various groups of mice, and it can be seen that: the normal control group (A) mice had well-arranged myocardial tissues and a complete structure. The mouse cardiac fibers in DNR group (B) are broken and arranged disorderly. The mouse cardiac fibers of the DNR + albumin peptide group (C), the DNR + wheat oligopeptide group (D), the DNR + soybean peptide group (E) and the DNR + corn oligopeptide group (F) are arranged orderly.
The above-described embodiments are merely preferred embodiments of the present invention, and not intended to limit the scope of the invention, so that equivalent changes or modifications in the structure, features and principles described in the present invention should be included in the claims of the present invention.
Claims (6)
1. The application of the bioactive peptide in preparing the medicine for preventing and treating the cardiotoxicity of anthracycline medicines.
2. The use of the bioactive peptide of claim 1 in the preparation of a medicament for the prevention or treatment of cardiotoxicity caused by anthracyclines, wherein the bioactive peptide is albumin peptide, wheat oligopeptide, soybean peptide or corn oligopeptide.
3. The use of a biologically active peptide according to claim 1 for the manufacture of a medicament for the prevention or treatment of cardiotoxicity of anthracyclines, wherein said anthracyclines are doxorubicin or daunorubicin.
4. The use of the bioactive peptide according to claim 1 for the preparation of a medicament for the prevention and treatment of anthracycline cardiotoxicity, wherein said medicament for the prevention and treatment of anthracycline cardiotoxicity is a medicament for the prevention and treatment of decrease in left ventricular ejection fraction and/or left ventricular short axis shortening rate caused by anthracycline.
5. The use of the bioactive peptide according to claim 1 in the preparation of a medicament for preventing and treating anthracycline cardiotoxicity, wherein the medicament for preventing and treating anthracycline cardiotoxicity is a medicament for preventing and treating increase in serum lactate dehydrogenase activity and/or decrease in serum glutathione content caused by anthracycline.
6. The application of the bioactive peptide in preparing the medicine for preventing and treating anthracycline cardiotoxicity is characterized in that the medicine for preventing and treating anthracycline cardiotoxicity is a medicine for preventing and treating myocardial superoxide dismutase activity reduction and/or cardiac malondialdehyde content increase caused by anthracycline medicines.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140057861A1 (en) * | 2012-08-21 | 2014-02-27 | Genesys Research Institute | Compositions and methods for treating or preventing anthracycline induced cardiotoxicity |
| CN105581242A (en) * | 2015-12-21 | 2016-05-18 | 安徽省佛子岭面业有限公司 | Wheat oligopeptide zinc-rich radix platycodonis nutritive noodles |
| CN107596340A (en) * | 2017-10-27 | 2018-01-19 | 河南省医药科学研究院 | Application of the soybean protein isolate in preventing or treating the myocardium toxicity of anthracene ring antitumor medicinal initiation |
| CN110338326A (en) * | 2019-07-10 | 2019-10-18 | 中慈保健品科技开发有限公司 | Assist in the treatment of the soybean peptide compounding solid beverage and its preparation method and application of cardiovascular and cerebrovascular |
| CN110639004A (en) * | 2019-10-15 | 2020-01-03 | 河南省医药科学研究院 | Application of albumin as anthracycline antibiotic cardiotoxicity inhibitor |
| CN111450230A (en) * | 2020-06-08 | 2020-07-28 | 武汉体育学院 | Application of corn oligopeptide in intervention of myocardial injury |
-
2021
- 2021-09-03 CN CN202111032568.8A patent/CN113694185B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140057861A1 (en) * | 2012-08-21 | 2014-02-27 | Genesys Research Institute | Compositions and methods for treating or preventing anthracycline induced cardiotoxicity |
| CN105581242A (en) * | 2015-12-21 | 2016-05-18 | 安徽省佛子岭面业有限公司 | Wheat oligopeptide zinc-rich radix platycodonis nutritive noodles |
| CN107596340A (en) * | 2017-10-27 | 2018-01-19 | 河南省医药科学研究院 | Application of the soybean protein isolate in preventing or treating the myocardium toxicity of anthracene ring antitumor medicinal initiation |
| CN110338326A (en) * | 2019-07-10 | 2019-10-18 | 中慈保健品科技开发有限公司 | Assist in the treatment of the soybean peptide compounding solid beverage and its preparation method and application of cardiovascular and cerebrovascular |
| CN110639004A (en) * | 2019-10-15 | 2020-01-03 | 河南省医药科学研究院 | Application of albumin as anthracycline antibiotic cardiotoxicity inhibitor |
| CN111450230A (en) * | 2020-06-08 | 2020-07-28 | 武汉体育学院 | Application of corn oligopeptide in intervention of myocardial injury |
Non-Patent Citations (2)
| Title |
|---|
| 李永生 等主编: "乳腺癌内科综合治疗策略与临床实践", 科学技术文献出版社, pages: 395 * |
| 游普云: "四种生物活性肽基于抗氧化作用的药理活性研究", 中国优秀硕士学位论文全文数据库, 15 May 2022 (2022-05-15), pages 395 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114259552A (en) * | 2021-12-14 | 2022-04-01 | 河南省医药科学研究院 | Application of bioactive peptide in preparation of acute kidney injury protective agent |
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