CN110960671A - New application of Elabela polypeptide and medicine thereof - Google Patents
New application of Elabela polypeptide and medicine thereof Download PDFInfo
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- CN110960671A CN110960671A CN201911355148.6A CN201911355148A CN110960671A CN 110960671 A CN110960671 A CN 110960671A CN 201911355148 A CN201911355148 A CN 201911355148A CN 110960671 A CN110960671 A CN 110960671A
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention discloses an application of Elabela polypeptide in preparing a medicament or functional food for preventing and/or treating diseases related to chronic kidney injury, and a medicament, wherein the diseases related to chronic kidney injury comprise: chronic renal insufficiency due to hypertension; or (ii) chronic renal insufficiency with hypertension. The Elabela polypeptide has stable blood pressure reduction, can effectively relieve the glomerular pathological injury of SD rats induced by deoxycorticosterone, reduce the discharge of microalbuminuria, relieve the development of kidney fibrosis and reduce the expression of inflammatory factors in kidney tissues, and has obvious effect on treating chronic kidney injury; meanwhile, the Elabela polypeptide is an endogenous hormone synthesized by a human body, is expressed in kidney tissues, and has smaller toxic and side effects compared with the existing medicament for treating chronic kidney injury.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a new application of Elabela polypeptide and a medicine thereof.
Background
Chronic renal insufficiency affects 8-16% of the world population and has become a worldwide public health and wellness problem. Research shows that chronic renal insufficiency not only affects the urinary system, but also is closely related to cardiovascular and cerebrovascular diseases, hypertension, diabetes and the like. In high-income countries and middle-income countries, hypertension has become the second leading cause of chronic renal insufficiency, and in China, the incidence rate of hypertensive renal injury is increasing in recent years. Chronic renal insufficiency caused by hypertension is hidden, clinical symptoms at the early stage of the disease are atypical, and the early improvement of life style and the early drug intervention treatment can reduce the occurrence of end-stage renal failure, contribute to improving the life quality of patients and reduce medical expenses. The chronic renal insufficiency pathology caused by hypertension is often manifested by ischemic changes in the glomeruli as well as by tubular atrophy and interstitial fibrosis. The continuous hypertension stimulation increases the pressure of the small artery entering the glomerulus, expands the lumen, loses the self-regulation ability, and the glomerulus is in a continuous high-filtration state, so that albuminuria and dominant albuminuria appear. And ischemic change of glomerulus causes the capillary loop to shrink or collapse, the renal capsule is filled with collagen substances, and finally the glomerulus is hardened and shrunk.
At present, the treatment mode of chronic renal insufficiency is very limited, for the azotemia stage (compensatory stage) of chronic renal insufficiency, the kidney protection treatment mainly takes traditional Chinese medicines and Chinese traditional medicines as main medicines, the curative effect lacks high-level evidence of the medicine, for the renal insufficiency of the decompensation stage of chronic renal insufficiency, namely the end stage renal insufficiency, no effective medicine can reverse the renal function at present, the medicine treatment mainly maintains the water electrolyte and acid-base balance, corrects anemia and the like, the life style improvement aspect mainly controls the risk factors of the kidney damage caused by blood pressure, blood sugar, blood fat, high salt and the like, avoids the excessive fatigue and cold, and delays the further deterioration of the renal function as far as possible, for the chronic renal insufficiency caused by hypertension or the hypertension secondary to the chronic renal insufficiency, and the traditional treatment medicines mainly comprise Angiotensin Converting Enzyme Inhibitors (ACEi)/angiotensin II receptor Antagonists (ARB), calcium antagonists (CCB), diuretics, β -blockers, α -blockers and the like.
The protective effect of the drugs on the kidney is mainly to reduce the circulating blood pressure and the renal cystic pressure, but the effect of reducing the renal inflammation, improving the renal function and reversing the renal fibrosis is very limited, Angiotensin Converting Enzyme Inhibitor (ACEi)/angiotensin II receptor Antagonist (ARB) is a commonly used antihypertensive drug for early stage chronic renal insufficiency, the antihypertensive drug is proved to have the effects of reducing proteinuria and improving the renal function, but the antihypertensive effect is weaker than that of a calcium antagonist, and the ARB is forbidden for patients with end stage renal failure (not dialysis) and bilateral renal artery stenosis and pregnant women, if the patients have renal insufficiency or a high dose of the ACE/ACE inhibitor, the calcium antagonist (CCB) is the most potassium antihypertensive drug in the hypertensive nephropathy, the antihypertensive effect is obvious, the blood potassium and the renal function level need to be strictly monitored, in addition, the angiotensin converting enzyme inhibitor can be obviously coughed after being taken by 10 percent of the patients, the calcium antagonist (CCB) is the most potassium antihypertensive drug in the hypertensive nephropathy, the antihypertensive effect is obvious, the second-line adverse effect is caused by the general hypotensive dysfunction, the short-loop edema is easily caused by other hypolipidemic drugs, such as α combined adverse effects.
The polypeptide small molecular hormone ELABELA/Toddler/Apela (ELA) is a novel endogenous peptide ligand of a G protein coupled receptor APJ, and plays an important role in various pathophysiological processes of embryonic stage and adult stage. A number of recent studies have shown that ELA can protect the cardiovascular system by promoting angiogenesis, regulating cardiac and vascular function, etc. However, the use of elabel polypeptides in the treatment of chronic renal injury associated with hypertension is not known.
Disclosure of Invention
Based on the above technical problems, the present invention aims to provide an elabel polypeptide for use in preventing and/or treating chronic kidney injury and a medicament thereof.
In order to achieve the purpose, the invention adopts the following technical scheme: application of Elabela polypeptide in preparation of medicines or functional foods for preventing and/or treating diseases related to chronic kidney injury.
As a preferred embodiment, the disease associated with chronic kidney injury includes: chronic renal insufficiency due to hypertension; or (ii) chronic renal insufficiency with hypertension.
The Elabela polypeptide can be used for preventing and/or treating chronic renal insufficiency or chronic renal insufficiency combined hypertension caused by hypertension by reducing the blood pressure level, obviously reducing the glomerular pathological injury area, obviously reducing the albumin excretion water level and the blood urea nitrogen level, obviously reducing the protein level of collagen fibers Col I in renal cortex tissues and renal medullary tissues, obviously reducing the protein level of α -SMA in the renal cortex tissues and the renal medullary tissues, obviously reducing the expression level of IL-1 β in serum, obviously reducing the expression level of NLRP3 in the renal cortex tissues and the renal medullary tissues and obviously reducing the expression levels of interleukins IL-1 β, IL-18 and MCP-1 in the renal cortex tissues and the renal medullary tissues.
Preferably, the elabel polypeptide is the sole or primary active ingredient in the medicament or functional food.
Another object of the present invention is to provide a pharmaceutical composition comprising an effective amount of elabel polypeptide, and at least one pharmaceutically acceptable carrier or excipient.
Preferably, the elabel polypeptide is the sole or primary active ingredient of the pharmaceutical composition. To enhance the therapeutic effect, the elabel polypeptides may also be combined with other drugs.
The invention also aims to provide a unit dose pharmaceutical composition, which comprises 0.001-5 wt% of Elabela polypeptide.
As a preferred embodiment, the pharmaceutical composition comprises 0.005 wt%, 0.1 wt%, 1.5 wt%, or 2.5 wt% of elabel polypeptide.
Preferably, the pharmaceutical composition is in the form of one of tablets, capsules, granules, oral liquid, sustained release agent, controlled release agent or injection.
Preferably, the pharmaceutical composition can be prepared into sustained-release preparations, including but not limited to sustained-release tablets (coated tablets, matrix tablets, multilayer tablets), sustained-release pills, sustained-release capsules (enteric capsules, medicinal resin capsules, film-coated capsules).
As a preferred embodiment, the pharmaceutical composition of the present invention can be made into sustained release tablets, and the matrix of the tablet includes but is not limited to: gelatin, pectin, or nanoparticles. The tablet may also include one or more pharmaceutically acceptable excipients including, but not limited to, fillers, glidants and lubricants, and other functional ingredients such as buffers, stabilizers, solubilizers, surfactants, and the like may also be included in the formulation in order to improve or optimize drug release and/or ensure drug stability in the formulation. The preparation method of the sustained-release tablet adopts the traditional tablet production method, including but not limited to a direct compression method, a rolling method or a re-pressing method, and the specific selection method is determined by the property of the formula.
In the present situation, it is necessary to effectively reduce blood pressure and control the level of proteinuria in chronic renal insufficiency caused by hypertension or a hypertensive complication secondary to chronic renal insufficiency. The existing treatment means usually comprises that clonidine, bixin or betalenk hypotensor is given to a patient to control blood pressure, and simultaneously, 'shenshuaining' is given to protect the kidney, but the treatment mode has poor effect on patients with chronic renal dysfunction of more than 3 stages, most patients still have a large amount of proteinuria, and the hypertension and the progressive creatinine increase are still difficult to control under the condition of using two hypotensor.
Experiments prove that the Elabela polypeptide can effectively relieve the arterial pressure of SD rats induced by deoxycorticosterone, and the blood pressure is stably reduced, so that the effect of stably reducing the blood pressure can be achieved within 10 days; meanwhile, the composition can effectively relieve deoxycorticosterone-induced glomerular pathological injury of SD rats, reduce the discharge of urine microalbumin, relieve the development of kidney fibrosis, reduce the expression of inflammatory factors in kidney tissues, and has a protective effect on the kidney, and clinical tests prove that El abela polypeptide patients have remarkable treatment effects on chronic renal insufficiency and hypertension, and the total effective rate is up to 88.6%.
Compared with the prior art, the invention has the following beneficial effects:
clinical tests prove that the Elabela polypeptide can effectively treat chronic renal insufficiency or chronic renal insufficiency combined hypertension diseases caused by hypertension, is an endogenous hormone synthesized by a human body, has smaller toxic and side effects compared with the existing synthetic medicine, and makes remarkable progress compared with the prior art.
Drawings
FIG. 1A shows that after the SD rat model is successfully made, ELA expression level changes are detected in a control group and an administration group by applying an immunohistochemical principle; b is a statistical graph of mean arterial pressure of groups of deoxycorticosterone-induced SD rats by ELA;
FIG. 2 is a graph of the effect of ELA on deoxycorticosterone-induced SD rat kidney weight, glomerular pathological injury, urinary albumin, blood urea nitrogen;
wherein A is a statistical chart of the ratio of the kidney to the self weight of the rat; b is a representation picture of glomerular pathological injury observed by PAS dyeing; c is a statistical chart of glomerular pathological injury; d is a statistical chart of urinary albumin excretion levels; e is a statistical chart of blood urea nitrogen levels;
FIG. 3 is a graph of the effect of ELA on deoxycorticosterone-induced collagen expression;
wherein, A is a damage representation diagram of kidney collagen fiber Col I (collagen fiber I) detected by sirius red staining; b is a kidney cortex collagen fiber Col I statistical chart; c is a Col I statistical chart of kidney medulla collagen fibers; d is a protein level and gray level analysis chart for detecting collagen fibers Col I of renal cortex tissues through western blot; e is a protein level and gray level analysis chart for detecting the kidney medullary tissue collagen fiber Col I through western blot;
FIG. 4 is a graph of the effect of ELA on deoxycorticosterone-induced renal fibrosis, wherein A is a graph of protein level and gray scale analysis of renal cortical tissue α -SMA (α -smooth muscle actin) using a western blot, and B is a graph of protein level and gray scale analysis of renal medullary tissue α -SMA using a western blot;
FIG. 5 is a graph showing the effect of ELA on the expression of inflammatory factors in serum and kidney tissue induced by deoxycorticosterone, wherein A is a statistical graph of IL-1 β (interleukin 1 β) expression in serum detected by ELISA, B is a statistical graph of NLRP3 expression in kidney cortex tissue detected by fluorescence quantitative PCR, C is a statistical graph of NLRP3 expression in kidney medullary tissue detected by fluorescence quantitative PCR, D is a statistical graph of interleukin IL-1 β -18 (interleukin 18) and MCP-1 (monocyte chemotactic protein-1) expression in kidney cortex tissue detected by fluorescence quantitative PCR, and E is a statistical graph of interleukin IL-1 β, IL-18 and MCP-1 expression in kidney medullary tissue detected by fluorescence quantitative PCR.
Detailed Description
The present invention will be described in further detail below with reference to specific embodiments of examples. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples.
In the examples, the experimental methods used were all conventional methods unless otherwise specified, and the materials, reagents and the like used were commercially available without otherwise specified.
EXAMPLE one, sustained Release tablet
The preparation method comprises the following steps:
weighing the raw Elabela polypeptide, gelatin and lactose according to the prescription amount, respectively, sieving with a 100-mesh sieve, mixing well, adding a proper amount of polyvidone K30 to prepare a soft material, granulating with a 24-mesh standard sieve, drying at 50 ℃ for 1.0 h.20-mesh sieve, and finishing; adding magnesium stearate, and making into tablet.
EXAMPLE two sustained Release tablets
| Composition (I) | Dosage of |
| Elabela polypeptides | 0.1wt％ |
| Gelatin | 40.0wt％ |
| Lactose | 4.0wt％ |
| Magnesium stearate | 2.0wt％ |
| Povidone K30 (3%) | Balance of |
The preparation method is as in example one.
EXAMPLE III sustained Release tablet
| Composition (I) | Dosage of |
| Elabela polypeptides | 1.5wt％ |
| Gelatin | 40.0wt％ |
| Lactose | 3.0wt％ |
| Magnesium stearate | 2.0wt％ |
| Povidone K30 (3%) | Balance of |
The preparation method is as in example one.
Test example I, animal experiment
1.1 test methods
18 SD rats were collected and divided into 3 groups, control group, model group and ELA polypeptide treatment group, after single nephrectomy. The control group (n ═ 6) drinking tap water; model group (n-6) and ELA polypeptide treatment group (n-6) by placing 150mg/kg DOCA particles subcutaneously and administering 1% NaCl water; the model group gives high expression to the plasmid transfected with ELA polypeptide, and the transfection steps are as follows: isoflurane inhalation anesthesia of mononephrectomized rats, cutting open the skin of the rats along the ventral midline, and exposing the left kidney; clamping left renal artery and vein with vascular clamp to make kidney ischemia; mixing 400ul of a solution containing 50ug of target vector DNA with 25% of a microbubble contrast agent according to a volume ratio of 2:1, injecting 600ul of the target vector transfection mixture into the left renal artery by using a 30G needle injector, and allowing the needle to stay in the renal artery for 30s after injection; carrying out ultrasonic treatment for 2 minutes after injection, loosening a vascular clamp, recovering renal blood flow supply, and suturing a wound; the analgesic and sulfanilamide were given 3 days after surgery to resist infection. The time for molding and administration was three weeks.
2. The result of the detection
2.1 mean arterial pressure statistics for groups of rats
The blood pressure of each group of animals is detected by a wireless remote sensing blood pressure monitor, the detection result is shown in figure 1, and as can be seen from figure 1, compared with a normal group, the blood pressure of the molding group is obviously increased, so that the success of molding is proved; compared with the modeling group, the blood pressure of the Elabela polypeptide group starts to be remarkably reduced on day 12, and the blood pressure is stably reduced by comparing the results of the blood pressure on day 12-21.
2.2 statistics of Kidney weight, glomerular pathological Damage, urinary Albumin, blood Urea Nitrogen
The detection result is shown in fig. 2, and as can be seen from a graph in fig. 2, the kidney weight of the model-made rats is significantly increased compared with the kidney weight of the normal group, and has significant difference (P < 0.05); compared with the modeling group, the weight of the kidney of the Elabela polypeptide group is obviously reduced, and the obvious difference exists (P is less than 0.05);
through the HE staining method, as can be seen from the B and C graphs in FIG. 2, compared with the modeling group, the Elabela polypeptide group can obviously reduce the glomerular pathological injury area, and has a significant difference (P < 0.05) compared with the modeling group, which indicates that the Elabela polypeptide can effectively relieve the low glomerular pathological injury.
The detection result is shown in the figure by a detection kit for urine albumin and urea nitrogen: as can be seen from the D and E plots in fig. 2, the elabel polypeptides significantly reduced albumin excretion water and blood urea nitrogen levels compared to the model group, and significantly differed from the model group by (P < 0.05).
2.3 collagen expression
The collagen proliferation condition is detected by a sirius red staining method of kidney tissues, the detection result is shown in fig. 3, and as can be seen from fig. 3, compared with the modeling group, the elabala polypeptide group can effectively relieve the damage of kidney collagen fibers Col I (collagen fibers I), the kidney cortical collagen fibers Col I and the kidney medullary collagen fibers Col I are remarkably reduced compared with the modeling group, the protein level of the kidney cortical tissue collagen fibers Col I and the protein level of the kidney medullary collagen fibers Col I are remarkably reduced compared with the modeling group, and the significant difference exists (P < 0.05).
2.4 renal fibrosis
The index protein α -SMA of fibrosis is detected by the western blot method, the detection result is shown in figure 4, and as can be seen from figure 4, compared with the modeling group, the Elabela polypeptide group can obviously reduce the protein level of renal cortex tissue α -SMA (α -smooth muscle actin) and the protein level of renal medulla tissue α -SMA, and has obvious difference (P < 0.05).
2.5 expression of inflammatory factors in serum and Kidney tissues
The detection result is shown in figure 5, and compared with the modeling group, the Elabela polypeptide group can obviously reduce the expression level of IL-1 β (interleukin 1 β) in serum, the expression level of NLRP3 in renal cortical tissue, the expression level of NLRP3 in renal medullary tissue, the expression level of interleukin IL-1 β -18 (interleukin 18), MCP-1 (monocyte chemotactic protein-1) in renal cortical tissue and the expression level of interleukin IL-1 β -18 and MCP-1 in renal medullary tissue, and has obvious difference (P < 0.05) in the detection result.
Test example two, clinical test
2.1 general data
86 patients with chronic renal dysfunction and hypertension in stage 3 are selected, 53 men and 33 women are selected, the average age is 52.56 +/-3.62 years old, 86 patients are randomly divided into two groups, the two groups are divided into a control group and a treatment group, both patients accord with the national diagnostic standard of renal dysfunction and hypertension, and the general data of physical quality, mental state and the like of both patients do not have statistical significance and are comparable.
2.2 methods of treatment
Control group: the control group is given with a hypotensor of bixin + clonidine + kidney-protecting drug of shenshuaining, wherein:
the same time of new year, once a day, one tablet at a time; clonidine, once a day, one tablet at a time; shenshuaining, three times a day, 3-6 granules (adjusted according to the condition of a patient) each time, and a treatment course is 45 days.
Treatment groups: patients in the treatment group were administered a sustained release tablet of the example of the invention orally, one tablet at a time, 2 times/d; the treatment period of 10 weeks is 1 treatment period, all patients are treated for 1 treatment period continuously, other similar medicines cannot be taken in the treatment period, the blood pressure of the patients is regularly detected in the treatment period, the administration can be stopped if the blood pressure is reduced to a target level, and the blood pressure reduction target of 1 treatment period is as follows: the blood pressure is less than 130/100mmHg (125/75 mmHg is required for patients with 24h urine protein content more than 1 g). Two weeks after treatment, a relevant review was performed.
2.3 therapeutic criteria
According to the relevant standards of clinical drug research provided by SFDA, ① has significant effect that diastolic pressure is reduced by more than 10mmHg and reaches normal after treatment, or the reduction degree is more than 20mmHg, ② is effective that diastolic pressure is reduced within 10mmHg and reaches normal, or the reduction range is 10 mmHg-20 mmHg, ③ is ineffective, the expected standards are not achieved after treatment, and the renal functions of patients are subjected to relevant detection, and the experimental results are shown in the following table 1.
Wherein, the total effective rate (%) + is significant efficiency (%) + effective rate (%)
TABLE 1 results of clinical trials
| Group of | Number of examples | Show effect | Is effective | Invalidation | Total effective |
| Control group | |||||
| 43 | 5 | 9 | 29 | 32.5 | |
| Treatment group | |||||
| 43 | 11 | 27 | 5 | 88.4％ |
From the above table, the pharmaceutical composition of the invention has a total effective rate of 88.4% for chronic renal dysfunction combined with hypertension in the 3 rd phase, while most patients still have a lot of proteinuria when the existing antihypertensive drug is used in combination with the kidney-protecting drug, and the hypertension and the progressive creatinine increase are still difficult to control under the condition of using two antihypertensive drugs, and the total effective rate is only 32.5%.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
- Use of elabel polypeptides in the manufacture of a medicament or functional food for the prevention and/or treatment of a disease associated with chronic kidney injury.
- 2. The use of claim 1, wherein the disease associated with chronic kidney injury comprises: chronic renal insufficiency due to hypertension; or (ii) chronic renal insufficiency with hypertension.
- 3. The use of claim 1 or 2, wherein the elabel polypeptide prevents and/or treats chronic renal insufficiency or chronic renal insufficiency combined hypertension caused by hypertension by reducing blood pressure levels, significantly reducing the area of glomerular pathological injury, significantly reducing albumin excretion water levels and blood urea nitrogen levels, significantly reducing the protein levels of collagen fibers, ColI, in renal cortical tissue and renal medullary tissue, significantly reducing the protein levels of α -SMA, significantly reducing the expression level of IL-1 β in serum, significantly reducing the expression level of NLRP3 in renal cortical tissue and renal medullary tissue, and significantly reducing the expression levels of interleukins IL-1 β, IL-18 and MCP-1 in renal cortical tissue and renal medullary tissue.
- 4. The use according to any one of claims 1 to 3, wherein the Elabela polypeptide is the sole or primary active ingredient in the medicament or functional food.
- 5. A pharmaceutical composition comprising an effective amount of an elabel polypeptide, and at least one pharmaceutically acceptable carrier or excipient.
- 6. The pharmaceutical composition of claim 5, wherein the Elabela polypeptide is the sole or primary active ingredient in the pharmaceutical composition.
- 7. A pharmaceutical composition with unit dose, which is characterized by comprising 0.001-5 wt% of Elabela polypeptide.
- 8. The unit dose pharmaceutical composition of claim 7, wherein said pharmaceutical composition comprises 0.005 wt%, 0.1 wt%, 1.5 wt%, or 2.5 wt% of the elabel polypeptide.
- 9. The unit-dose pharmaceutical composition according to claim 7 or 8, wherein the pharmaceutical composition is in the form of one of a tablet, a capsule, a granule, an oral liquid, a sustained release agent, a controlled release agent, or an injection.
- 10. The unit dose pharmaceutical composition of claim 9, wherein said pharmaceutical composition is in the form of a sustained release formulation.
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| CN111973579A (en) * | 2020-08-07 | 2020-11-24 | 广州中医药大学(广州中医药研究院) | Application of butyrate in preparation of medicines for treating or preventing kidney injury |
| CN112007144A (en) * | 2020-08-24 | 2020-12-01 | 广州中医药大学(广州中医药研究院) | Application of Elabela polypeptide in preparation of antioxidant product |
| CN114558115A (en) * | 2022-03-07 | 2022-05-31 | 中山大学附属第八医院（深圳福田） | Application of ELABELA in improving survival and migration of adipose-derived stem cells |
| CN116617368A (en) * | 2023-05-30 | 2023-08-22 | 杭州师范大学 | Application of Elabela in vascular endothelial cell aging resistance |
| CN116655773A (en) * | 2022-11-07 | 2023-08-29 | 吉林大学第一医院 | Peptide hormone Elabela mutant and application thereof in heart and kidney syndrome |
| WO2024027553A1 (en) * | 2022-08-03 | 2024-02-08 | 无锡市华盛康肽生物技术有限公司 | Bifunctional fusion protein and use thereof |
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| CN111973579A (en) * | 2020-08-07 | 2020-11-24 | 广州中医药大学(广州中医药研究院) | Application of butyrate in preparation of medicines for treating or preventing kidney injury |
| CN112007144A (en) * | 2020-08-24 | 2020-12-01 | 广州中医药大学(广州中医药研究院) | Application of Elabela polypeptide in preparation of antioxidant product |
| CN114558115A (en) * | 2022-03-07 | 2022-05-31 | 中山大学附属第八医院（深圳福田） | Application of ELABELA in improving survival and migration of adipose-derived stem cells |
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| WO2024027553A1 (en) * | 2022-08-03 | 2024-02-08 | 无锡市华盛康肽生物技术有限公司 | Bifunctional fusion protein and use thereof |
| CN116655773A (en) * | 2022-11-07 | 2023-08-29 | 吉林大学第一医院 | Peptide hormone Elabela mutant and application thereof in heart and kidney syndrome |
| CN116655773B (en) * | 2022-11-07 | 2023-12-22 | 吉林大学第一医院 | Peptide hormone Elabela mutant and application thereof in heart and kidney syndrome |
| CN116617368A (en) * | 2023-05-30 | 2023-08-22 | 杭州师范大学 | Application of Elabela in vascular endothelial cell aging resistance |
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