CN113425707B - Application of azelaic acid in preventing cardiotoxicity of anthracycline antitumor drugs - Google Patents
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- A61P9/00—Drugs for disorders of the cardiovascular system
Abstract
The invention belongs to the technical field of medicines for preventing and treating cardiotoxicity, and particularly relates to application of azelaic acid in preventing cardiotoxicity of anthracycline antitumor medicines. Azelaic acid can reduce cardiotoxicity caused by anthracycline antineoplastic drugs, improve oxidative stress reaction and relieve cell apoptosis, thereby reducing lethality caused by adriamycin cardiotoxicity. The invention can be used for preventing and relieving the cardiotoxicity induced by anthracycline antitumor drugs and has clinical practicability.
Description
Technical Field
The invention belongs to the technical field of medicines for preventing and treating cardiotoxicity, and particularly relates to application of azelaic acid in preventing cardiotoxicity of anthracycline antitumor medicines.
Background
The anthracycline drugs comprise adriamycin, daunorubicin, aclarubicin, idarubicin, epirubicin, mitoxantrone and the like, wherein adriamycin (adriamycin), also called Doxorubicin (DOX), is one of broad-spectrum antitumor drugs commonly used in clinic, is widely applied to treatment of tumors such as leukemia, solid tumors, lymphoma, breast cancer and the like, and achieves good curative effect. However, such drugs have a high affinity for myocardial tissue, produce cumulative and dose-dependent cardiotoxicity, further progress to irreversible myocardial damage, eventually leading to congestive heart failure, and may be life-threatening, and such cardiotoxicity may occur shortly after administration, during administration, after treatment, and even years or decades after discontinuation of administration, thus severely limiting their clinical use.
It is currently widely believed that increased oxidative stress, calcium overload, disorders of energy metabolism, mitochondrial damage, apoptosis, etc., caused by reactive oxygen radicals and lipid peroxidation play an important role in DOX cardiotoxicity. In order to solve the limitation of clinical application of anthracyclines, researchers have developed a large number of research on prevention and treatment adjuvant drugs for cardiotoxicity caused by anthracyclines, which mainly include mitochondrial protective agents, apoptosis inhibitors, iron ion chelators, antioxidants, radical scavengers, and the like.
Various chemical substances are researched, the iron ion chelating agent dexrazoxane (dexrazoxane) is the only protective agent approved by the FDA at present and used for preventing and treating the cardiotoxicity of anthracycline antitumor drugs, the curative effect is obvious, and the dexrazoxane is applied to clinic, but the drug treatment has certain defects, so that serious bone marrow suppression can be caused, and the activity of adriamycin on certain malignant tumors is influenced; secondly, the drug is expensive and can only be slowly pushed after being dissolved in lactic acid solution, so that the application of the drug is greatly limited.
Aiming at the toxic and side effects of anthracyclines in clinical treatment, researchers have designed and synthesized pectin-adriamycin conjugates and xyloglucan-adriamycin prodrug preparations and the like, so that the biological distribution of the drugs is changed, the pharmacokinetics and pharmacodynamics properties are improved, however, the conjugates are expensive in manufacturing cost and low in drug loading rate, and the treatment effect on tumors is influenced. In addition, the liposome preparation of the anthracycline antitumor drug can reduce the accumulation of the drug in the heart and increase the distribution of the drug in tumor tissues, thereby relieving the dose-dependent acute toxicity, such as the marketed adriamycin liposome, daunorubicin liposome and the like, but the drug is encapsulated in the internal water phase, and the effect can be exerted only by releasing the drug from the liposome, and the preparation process of the liposome is complex, so the defects limit the wide application of the liposome preparation of the anthracycline antitumor drug. Therefore, there is an urgent need to find preventive measures that are effective in treatment and economical in price.
Disclosure of Invention
According to the defects in the prior art and in combination with the current research frontier, the invention provides the application of azelaic acid in preventing myocardial toxicity of anthracycline antitumor drugs, and the combined use of azelaic acid and anthracycline antitumor drugs reduces myocardial toxicity. Experiments prove that the azelaic acid can reduce the myocardial toxicity caused by the adriamycin, improve the oxidative stress reaction and relieve the apoptosis, thereby reducing the lethality caused by the adriamycin cardiotoxicity. The invention can be used for preventing and relieving adriamycin-induced myocardial toxicity and has clinical practicability.
The invention is realized by adopting the following technical scheme:
the invention provides application of azelaic acid in preventing cardiotoxicity of anthracycline antitumor drugs.
The invention also provides the application of azelaic acid as an anthracycline antitumor drug cardiotoxicity inhibitor.
Wherein the azelaic acid is 1, 7-dicarboxylheptane, and the structural formula is shown in formula I:
specifically, the anthracycline antitumor drug comprises at least one of adriamycin, daunorubicin, aclarubicin, idarubicin, epirubicin or mitoxantrone.
The application of the invention is used for preparing a medicine mixture and a medicine composition for inhibiting myocardial damage caused by anthracycline antitumor drugs.
Further, as a preferable embodiment of the present invention, the pharmaceutical mixture or the pharmaceutical composition comprises azelaic acid and anthracycline antitumor drugs.
The invention also provides a pharmaceutical mixture or a pharmaceutical composition, the active ingredient of which comprises azelaic acid,
the drug mixture or the drug composition has at least one of the following functions 1) to 5):
1) Preventing and/or treating cardiotoxicity of anthracycline chemotherapeutic agents;
2) Relieving myocardial cell lactate dehydrogenase caused by anthracycline chemotherapeutic drugs
3) Reducing the rise of active oxygen free radicals caused by anthracycline chemotherapeutic drugs;
4) Relieving myocardial cell lipid peroxidation caused by anthracycline chemotherapeutic drugs;
5) Relieve mitochondrial membrane depolarization and apoptosis caused by anthracycline chemotherapeutic drugs.
Specifically, the pharmaceutical mixture or the pharmaceutical composition is any pharmaceutically acceptable dosage form, including at least one of tablets, capsules, injections, granules, suspensions and solutions.
The core of the technology is that azelaic acid (azelaic acid), also called azelaic acid, is white to yellowish monoclinic prismatic crystal, acicular crystal or powder, belongs to one of medium-long chain binary acids, exists in flue-cured tobacco leaves, burley tobacco leaves and aromatic tobacco leaves, can be synthesized by a chemical method, and is applied to inhibiting the generation of active oxygen free radicals, inhibiting cell proliferation, resisting inflammation and the like. Azelaic acid is used as a non-antibiotic medicine for treating acne in local application, is not easy to generate drug resistance and is safe to use.
The detection results reflect that azelaic acid can obviously reduce the myocardial cytotoxicity and oxidative stress level induced by adriamycin, increase the activity of antioxidant enzyme and relieve the apoptosis condition, thereby deducing that azelaic acid can prevent and reduce the myocardial toxicity induced by adriamycin.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention provides a new idea and a new method for preventing cardiotoxicity caused by anthracycline antitumor drugs. The azelaic acid can be extracted from natural plants and synthesized by a chemical method, has no obvious adverse reaction, can be orally taken or locally applied, is easy to accept, and is beneficial to clinical popularization and application.
(2) The research of the invention finds that the myocardial cell toxicity caused by adriamycin can be obviously reduced in a cell model experiment, and the myocardial cell toxicity is specifically shown in that the oxidative stress level is obviously reduced, the activity of superoxide dismutase is increased, and the apoptosis rate is obviously reduced. The invention has obvious protection effect on cardiotoxicity induced by adriamycin, thereby expanding the clinical application of adriamycin.
Drawings
FIG. 1 is a graph comparing the effect of different concentrations of azelaic acid on the activity of doxorubicin H9c2 cardiomyocytes in example 1;
FIG. 2 is a graph comparing the effect of azelaic acid on LDH release from doxorubicin H9c2 cardiomyocytes in example 2;
FIG. 3 is a graph comparing the effect of azelaic acid on the ROS levels of cardiomyocytes in Adriamycin H9c2 in example 3;
FIG. 4 is a graph of the fluorescence signal intensity data of FIG. 3;
FIG. 5 is a graph comparing the effect of azelaic acid on the SOD levels of cardiomyocytes in Adriamycin H9c2 in example 4;
FIG. 6 is a graph comparing the effect of azelaic acid on MDA levels in cardiomyocytes of doxorubicin H9c2 in example 5;
FIG. 7 is a graph comparing the effect of azelaic acid on ATP levels in myocardial cells of doxorubicin H9c2 in example 6;
FIG. 8 is a graph comparing the effect of azelaic acid on apoptosis of doxorubicin H9c2 cardiomyocytes in example 7;
FIG. 9 is a graph of the fluorescence signal intensity data of FIG. 8;
FIG. 10 is a graph comparing the effect of azelaic acid on the mitochondrial membrane potential of doxorubicin H9c2 cardiomyocytes in example 8;
FIG. 11 is a graph of the fluorescence signal intensity data of FIG. 10.
Detailed Description
In order to make the purpose and technical solution of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings. The experimental methods described in the following examples are all conventional methods unless otherwise specified; those skilled in the art who do not specify any particular technique or condition in the examples, do so according to the techniques or conditions described in the literature of the art or according to the product specification; the reagents and materials are commercially available, unless otherwise specified.
The following examples employ the following materials:
the anthracycline antibiotics preferably comprise one of adriamycin, daunorubicin, aclarubicin, idarubicin, pirarubicin or mitoxantrone, and corresponding experiments are carried out by taking adriamycin as an example in the embodiment of the invention.
The cardiomyocytes were H9c2 cell lines and were stored at-80 ℃.
Dexrazoxane (DEXRA): purchased from the company Hubei Wildri chemical science and technology, inc.; cat No. Y694.
Azelaic acid (Aza): molecular formula C 9 H 16 O 4 CAS number 123-99-9, available from the company CeAnen peptide Biotech, inc.; cat number ETYSW201009-1.
DCFH-DA active oxygen ROS fluorescent probe: purchased from Dalian Melam Biotechnology Ltd; cat No. MB4682; the dosage is 1ml; incubation time is 15-60 min; fluorescence band: excitation wavelength 504nm, emission wavelength 529nm.
The CCK-8 kit is purchased from Dalian Meiren Biotechnology Limited company; the product number is MA0218-L-10000T.
LDH detection kit, purchased from Beijing Solaibao science and technology Co., ltd; cat No. BC0685.
The CuZn/Mn-SOD activity detection kit is purchased from Shanghai Biyuntian biotechnology limited company; the cargo number is S0103.
The TUNEL apoptosis detection kit is purchased from Shanghai Bin Yuntian biotechnology limited company; item number C1088.
An ATP detection kit purchased from Shanghai Bin Yuntian biotechnology limited company; cat # S0026B.
A lipid oxidation (MDA) detection kit, purchased from Shanghai Bin Yuntian biotechnology limited; item number S0131S.
A mitochondrial membrane potential detection kit (JC-1) purchased from Beijing Solaibao Tech Co., ltd; item number M8650-100T.
Cardiomyocyte complete medium solution: volume ratio 89% DMEM +10% FBS (FBS: fetal bovine serum, from the company Dalian Meilun Biotechnology Co., ltd.; cat # PWL 001) +1% diabody (diabody: penicillin/streptomycin solution, from the company Dalian Meilun Biotechnology Co., ltd.; cat # MA 0110)
Example 1 Effect of azelaic acid on myocardial cell Activity of Adriamycin H9c2
H9c2 cardiomyocytes were diluted 10 with medium 5 The cells were suspended in a volume of one ml and seeded in a 96-well plate, and 100. Mu.L of the cell suspension was added to each well, followed by drug treatment after 24 hours of culture. The control group, the positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and the azelaic acid solutions (each containing 5. Mu.M doxorubicin) at different concentrations (10. Mu.M, 20. Mu.M, 30. Mu.M, and 40. Mu.M) were each set. After 24h of culture, the activity of the cardiomyocytes was measured by CCK-8 cell viability assay, and the absorbance at 450nm was measured using a microplate reader.
The results are shown in figure 1, where "-" indicates a statistical difference compared to the blank group, P <0.05; "" indicates a statistical difference compared to the doxorubicin group, P <0.05. Relative to the cell activity of the control group of 120.06%, the cell activity of the 5 μ M doxorubicin (Dox) group of 44.33% and the cell activity of the positive control group of 121.46%, the cell activities were 110.02%, 64.19%, 49.00% and 38.96% respectively after the combined use of 10 μ M, 20 μ M, 30 μ M and 40 μ M azelaic acid (Aza). At the α =0.05 level, significance was observed for the 10 μ M Aza +5 μ M Dox group versus the 5 μ M Dox group, with 10 μ M Aza used in subsequent experiments.
Example 2 Effect of azelaic acid on Adriamycin H9c2 cardiomyocyte Lactate Dehydrogenase (LDH) Release
H9c2 cardiomyocytes were diluted 10 with medium 6 The cells were suspended in a volume of one mL and seeded in 6-well plates, 2mL of the cell suspension was added per well, and after 24 hours of culture, drug treatment was performed. A control group, a positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and a 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h of culture, measurement was performed using an LDH detection kit.
Referring to fig. 2, an "+" in the figure indicates that there was a statistical difference, P <0.05, compared to the blank group; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. The adriamycin group causes the content of lactate dehydrogenase in serum to be obviously increased, and compared with the control group, P is less than 0.05; the content of lactate dehydrogenase in the cell supernatant of the azelaic acid treatment group is close to that of the control group, and the statistical difference P is less than 0.05 compared with that of the adriamycin group.
Example 3 Effect of azelaic acid on Adriamycin H9c2 myocardial cell Reactive Oxygen Species (ROS) levels
H9c2 cardiomyocytes were diluted 10 with medium 6 The cells were suspended in a volume of one mL and seeded in 6-well plates, 2mL of the cell suspension was added per well, and after 24 hours of culture, drug treatment was performed. The control group, the positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and the 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h incubation, DCFH-DA probes were loaded, imaged with a confocal laser microscope (FIG. 3), and processed with ImageJ imagesThe software processes the image (fig. 4).
In figure 4 "-" indicates that there was a statistical difference compared to the blank group, P <0.05; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. Doxorubicin group caused a significant increase in ROS levels, P <0.05 compared to control group; the level of ROS in the azelaic acid treatment group is statistically different from that in the doxorubicin group by P <0.05, so that the ROS level is reduced, and the effect is better than that of a positive control.
Example 4 Effect of azelaic acid on Adriamycin H9c2 cardiomyocyte superoxide dismutase (SOD) levels
H9c2 cardiomyocytes were diluted 10 with medium 6 The cells were suspended in a volume of one mL and seeded in 6-well plates, 2mL of the cell suspension was added per well, and after 24 hours of culture, drug treatment was performed. A control group, a positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and a 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h of incubation, the procedure was followed according to the kit reagents (S0103, cuZn/Mn-SOD activity assay kit) instructions.
The results are shown in fig. 5, where "-" indicates that there was a statistical difference, P <0.05; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. The doxorubicin group caused a significant reduction in SOD levels, P <0.05 compared to the control group; compared with the adriamycin group, the statistic difference P of the SOD level of the azelaic acid treatment group is less than 0.05, and the SOD level is improved.
Example 5 Effect of azelaic acid on Adriamycin H9c2 cardiomyocyte Malondialdehyde (MDA) levels
H9c2 cardiomyocytes were diluted 10 with medium 6 Cell suspension/mL, and seeded in 6-well plates, 2mL of cell suspension per well, cultured for 24h, and then subjected to drug treatment. The control group, the positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and the 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h incubation, the assay kit reagents (S0131S, lipid oxidation (MDA) assay kit) were used according to the protocol.
Referring to fig. 6, the "-" in the figure indicates that there was a statistical difference, P <0.05; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. Doxorubicin group caused a significant increase in MDA levels, P <0.05 compared to control group; compared with the adriamycin group, the level of MDA in the azelaic acid treatment group has a statistical difference P <0.05, and the MDA level is reduced.
Example 6 Effect of azelaic acid on ATP levels in Adriamycin H9c2 cardiomyocytes
H9c2 cardiomyocytes were diluted 10 with medium 6 The cells were suspended in a volume of one mL and seeded in 6-well plates, 2mL of the cell suspension was added per well, and after 24 hours of culture, drug treatment was performed. The control group, the positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and the 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h of incubation, the assay kit reagents (S0026B, ATP assay kit) were used according to the instructions.
Referring to fig. 7, the "-" in the figure indicates that there was a statistical difference, P <0.05; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. The adriamycin group causes remarkable reduction of ATP content, and compared with a control group, P is less than 0.05; compared with the adriamycin group, the ATP content of the azelaic acid treatment group has statistical difference P <0.05, and the ATP content is increased.
Example 7 Effect of azelaic acid on Adriamycin H9c2 myocardial apoptosis
H9c2 cardiomyocytes were diluted 10 with medium 6 Cell suspension/mL, and seeded in 6-well plates, 2mL of cell suspension per well, cultured for 24h, and then subjected to drug treatment. A control group, a positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and a 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h of culture, the procedure was performed according to the TUNEL apoptosis assay kit (C1088, TUNEL apoptosis assay kit) instructions. After staining, the images were processed, photographed using a confocal laser microscope (fig. 8), and processed using ImageJ image processing software (fig. 9).
As shown in fig. 9, "-" in the figure indicates that there was a statistical difference, P <0.05; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. The adriamycin group causes a remarkable increase of the apoptosis rate, and compared with the control group, the P is less than 0.05; compared with the adriamycin group, the azelaic acid treatment group has statistical difference P <0.05, and the apoptosis rate is reduced.
Example 8 Effect of azelaic acid on mitochondrial Membrane potential of Adriamycin H9c2 cardiomyocytes
H9c2 cardiomyocytes were diluted 10 with medium 6 The cells were suspended in a volume of one mL and seeded in 6-well plates, 2mL of the cell suspension was added per well, and after 24 hours of culture, drug treatment was performed. The control group, the positive control group (20. Mu.M dexrazoxane + 5. Mu.M doxorubicin), and the 10. Mu.M azelaic acid (containing 5. Mu.M doxorubicin) solution group were each set. After 24h of incubation, the procedures were performed according to the kit reagent (M8650-100T, mitochondrial membrane potential assay kit (JC-1)) instructions. The images were processed, photographed using a confocal laser microscope (fig. 10), and processed using ImageJ image processing software (fig. 11).
Referring to fig. 11, an "+" in the figure indicates that there is a statistical difference, P <0.05, compared to the blank group; "#" indicates that there was a statistical difference compared to the doxorubicin group, P <0.05. The doxorubicin group significantly caused cell depolarization with P <0.05 compared to the control group; compared with the adriamycin group, the azelaic acid treatment group has a statistical difference P <0.05, and cell depolarization is relieved.
It is to be understood that the present invention has been described in detail with reference to the foregoing embodiments, and that modifications may be made by those skilled in the art, or equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (4)
1. The application of azelaic acid in preparing the medicine for preventing and inhibiting myocardial toxicity caused by antitumor chemotherapeutic adriamycin is characterized in that the medicine is a medicine mixture or a medicine composition, consists of azelaic acid and antitumor chemotherapeutic adriamycin, and has at least one function of the following 1) -5):
1) Preventing and/or treating myocardial toxicity caused by chemotherapeutic adriamycin;
2) Relieving myocardial cell lactate dehydrogenase caused by chemotherapy drug adriamycin;
3) Reducing the rise of active oxygen free radicals caused by the chemotherapeutic adriamycin;
4) Relieving myocardial cell lipid peroxidation caused by chemotherapeutic adriamycin;
5) Relieve mitochondrial membrane depolarization and apoptosis caused by chemotherapy drug adriamycin.
2. Use according to claim 1, wherein the azelaic acid is 1, 7-dicarboxylheptane having the formula shown in formula I:
3. The use according to claim 1, for the preparation of pharmaceutical mixtures, pharmaceutical compositions for the inhibition of myocardial damage caused by the antitumor drug doxorubicin.
4. The use according to claim 1, wherein the pharmaceutical mixture or composition is in any pharmaceutically acceptable dosage form, including at least one of a tablet, a capsule, an injection, a granule, a suspension and a solution.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011085000A2 (en) * | 2010-01-06 | 2011-07-14 | The University Of North Carolina At Chapel Hill | Fatty acid derivatives and analogs of drugs |
| CN105753921A (en) * | 2016-03-31 | 2016-07-13 | 沈阳药科大学 | Prodrug based on intestinal OCTN2 carrier protein design and preparation method thereof |
| CN106580942A (en) * | 2016-12-27 | 2017-04-26 | 武汉大学 | Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs |
| WO2018218242A1 (en) * | 2017-05-26 | 2018-11-29 | Epicentrx, Inc. | Methods and compositions for combination therapy |
| CN110946856A (en) * | 2019-12-09 | 2020-04-03 | 中国药科大学 | Pharmaceutical composition for preventing and treating anthracycline antibiotic cardiotoxicity and application thereof |
| EP3848025A1 (en) * | 2020-01-13 | 2021-07-14 | Professional Dietetics S.p.A. | Compositions comprising amino acids for use in the prevention and treatment of chemotherapy side effects |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20090326069A1 (en) * | 2008-06-30 | 2009-12-31 | Bltn, Llc | Azelaic acid ester compositions and methods for diagnosing and treating tissue conditions using azelaic acid ester compositions and proteinaceous biomarkers |
| ES2522167T3 (en) * | 2010-01-05 | 2014-11-13 | National Dong Hwa University | Anti-cancer formulation |
| WO2019108729A1 (en) * | 2017-12-01 | 2019-06-06 | Lunella Biotech, Inc. | Repurposcins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells |
| US11931330B2 (en) * | 2018-02-20 | 2024-03-19 | Korea University Research And Business Foundation | Composition for promoting skeletal muscle activity via induction of mitochondrial biogenesis comprising of azelaic acid as an active ingredient |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011085000A2 (en) * | 2010-01-06 | 2011-07-14 | The University Of North Carolina At Chapel Hill | Fatty acid derivatives and analogs of drugs |
| CN105753921A (en) * | 2016-03-31 | 2016-07-13 | 沈阳药科大学 | Prodrug based on intestinal OCTN2 carrier protein design and preparation method thereof |
| CN106580942A (en) * | 2016-12-27 | 2017-04-26 | 武汉大学 | Application of AZA (Azelaic Acid) in preparation of AML (Acute Myeloid Leukemia) resistant and chemosensitization drugs |
| WO2018218242A1 (en) * | 2017-05-26 | 2018-11-29 | Epicentrx, Inc. | Methods and compositions for combination therapy |
| CN110946856A (en) * | 2019-12-09 | 2020-04-03 | 中国药科大学 | Pharmaceutical composition for preventing and treating anthracycline antibiotic cardiotoxicity and application thereof |
| EP3848025A1 (en) * | 2020-01-13 | 2021-07-14 | Professional Dietetics S.p.A. | Compositions comprising amino acids for use in the prevention and treatment of chemotherapy side effects |
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