CN112773789B - Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling - Google Patents

Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling Download PDF

Info

Publication number
CN112773789B
CN112773789B CN202110277564.XA CN202110277564A CN112773789B CN 112773789 B CN112773789 B CN 112773789B CN 202110277564 A CN202110277564 A CN 202110277564A CN 112773789 B CN112773789 B CN 112773789B
Authority
CN
China
Prior art keywords
lactucin
heart failure
cardiac remodeling
pathological cardiac
application
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202110277564.XA
Other languages
Chinese (zh)
Other versions
CN112773789A (en
Inventor
陈希瑶
张富洋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Air Force Medical University of PLA
Original Assignee
Air Force Medical University of PLA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Air Force Medical University of PLA filed Critical Air Force Medical University of PLA
Priority to CN202110277564.XA priority Critical patent/CN112773789B/en
Publication of CN112773789A publication Critical patent/CN112773789A/en
Application granted granted Critical
Publication of CN112773789B publication Critical patent/CN112773789B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention relates to the technical field of biological medicines, in particular to application of lactucin in preparing a medicine for preventing and treating heart failure and pathological cardiac remodeling. The medicine takes lactucin as an effective component, and can be mixed with pharmaceutically acceptable, inert and nontoxic excipients or carrier auxiliary materials to prepare clinical medicines convenient for oral administration or intravenous application. Specifically, the application of lactucin in preparing a medicine for resisting heart failure, the application of lactucin in preparing a medicine for resisting cardiac insufficiency, the application of lactucin in preparing a medicine for resisting pathological cardiac remodeling, the effect of lactucin in preparing a medicine for resisting myocardial cell hypertrophy, the application of lactucin in preparing a medicine for resisting myocardial interstitial fibrosis and the application of lactucin in preparing a medicine for resisting myocardial cell death are disclosed.

Description

Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of lactucin in preparing a medicine for preventing and treating heart failure and pathological cardiac remodeling.
Background
Heart failure is a clinical syndrome manifested by the progression of various cardiovascular diseases such as coronary atherosclerotic heart disease, myocardial infarction, hypertension, myocarditis, cardiomyopathy and the like to the terminal stage, and is mainly manifested by various symptoms caused by cardiac insufficiency which cannot meet the blood supply requirement of the whole body organs. The key pathogenic mechanism of heart failure is pathological cardiac remodeling which is mainly manifested by myocardial cell hypertrophy, myocardial interstitial fibrosis and myocardial cell death, and how to effectively relieve the pathological cardiac remodeling becomes a bottleneck link for preventing and treating the heart failure and cardiac insufficiency.
Currently, clinical treatment and prevention of heart failure and cardiac insufficiency face the following 2-point limitations: (1) the number of the selected medicines is small; at present, the only medicines which have definite clinical evidence to support and can relieve pathological heart reconstruction and heart failure are beta-adrenoceptor blocking agents, angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and aldosterone receptor antagonists, which respectively have contraindications to limit the use of the medicines, so that the selection of medicines for clinically preventing and treating heart failure and pathological heart reconstruction is few; (2) the curative effect of the medicine is not good; the clinical data prove that the death rate of patients with the heart failure is as high as 50 percent within 5 years despite the optimized treatment of the existing medicaments, the long-term prognosis is even worse than that of some malignant tumors, and the curative effect of the existing clinical medicaments for preventing and treating the heart failure and pathologic cardiac remodeling is still not ideal. The burden of cardiovascular diseases in China is heavy, and the Chinese heart failure diagnosis and treatment guideline of 2018 indicates that the prevalence rate of heart failure in China is as high as 0.9 percent, and the number of patients is as high as 1000 thousands, so that the development of a novel and effective anti-heart failure and pathologic heart remodeling medicine is a technical key point for solving the problems of few medicine selections and poor effect in clinical prevention and treatment of heart failure.
Cichorium hirsutum is an annual herb of Cichorium in Compositae, and has significant medicinal value. Lactucopicin (lactucarin) is one of sesquiterpene components extracted from Cichorium hirsutum, and has chemical name of (3aR,4S,9aS,9bR) -9- (Hydroxymethyl) -6-methyl-3-methyl-2, 7-dioxo-2,3,3a,4,5,7,9a,9b-octahydroazuleno [4,5-b ]]furan-4-yl (4-hydroxyphenyl) acetate, CAS number 65725-11-3, molecular formula C23H22O7And the molecular weight is 410.42. The prior published technology mainly focuses on the extraction and preparation method of lactucin, and the patent application with the application number of 202011063090.0, the application date of 2020.09.30 and the name of lactucin and the application of lactucin as an anti-inflammatory component specifically discloses the application of lactucin in preparing anti-inflammatory drugs; the application of the medicinal material taking the lactucin as the active ingredient in preparing the medicine for preventing and treating the heart failure and the pathological cardiac remodeling is not known at present, the application discovers for the first time that the lactucin has the effect of remarkably preventing and treating the heart failure and the pathological cardiac remodeling, and the lactucin is mixed with a pharmaceutically acceptable, inert and nontoxic excipient or carrier auxiliary material to easily prepare the clinical medicine for resisting the heart failure and the pathological cardiac remodeling, which is convenient for oral administration or intravenous application.
Disclosure of Invention
In view of the technical defects, the invention aims to provide the application of lactucin in preparing medicines for preventing and treating heart failure and pathological cardiac remodeling.
In order to solve the technical problems, the invention adopts the following technical scheme:
application of lactucin in preparing medicine for preventing and treating heart failure and pathologic cardiac remodeling is provided.
Preferably, the heart failure and pathological cardiac remodeling are animal heart failure and pathological cardiac remodeling.
Preferably, the animal is an adult C57BL/6J mouse.
Preferably, the amount of lactucin in the mice with heart failure and pathological heart reconstruction is 30-100mg/kg body weight/day.
Preferably, the lactucin is applied to preparing the medicine for resisting cardiac insufficiency caused by heart failure and pathological cardiac remodeling.
Preferably, the lactucin is applied to preparing the medicines for resisting myocardial cell hypertrophy caused by heart failure and pathological cardiac remodeling.
Preferably, the lactucin is applied to preparing the medicines for resisting the myocardial interstitial fibrosis caused by heart failure and pathological cardiac remodeling.
Preferably, the lactucin is applied to preparing the medicines for resisting myocardial cell death caused by heart failure and pathological cardiac remodeling.
Preferably, the medicine is prepared from lactucin and an auxiliary material, wherein the auxiliary material is an excipient or a carrier auxiliary material.
Compared with the prior art, the invention has the beneficial effects that:
the application discovers for the first time that the lactucin serving as an effective component medicament can remarkably play the roles of preventing and treating heart failure, pathological cardiac remodeling and the like, such as cardiac insufficiency resistance, myocardial interstitial fibrosis resistance, myocardial cell hypertrophy resistance, myocardial cell death resistance and the like. Determining the effective dose range of the lactucin for preventing and treating heart failure and pathological cardiac remodeling of a myocardial infarction mouse model to be 30-100mg/kg body weight/day; wherein, the effect of the lactucin with the dosage of 100mg/kg body weight/day for preventing and treating the heart failure and the pathological reconstruction is equivalent to that of the prior clinical first-line medicament beta receptor blocker (taking metoprolol as an example) with the dosage of 250mg/kg body weight/day.
The lactuca sativa bitter element can be used as an effective component to be mixed with pharmaceutically acceptable, inert and nontoxic excipients or carrier auxiliary materials to prepare the anti-heart failure and pathological heart reconstruction medicines convenient for oral administration or intravenous application, and provides a potential and effective new medicine selection for clinically preventing and treating the heart failure and the pathological heart reconstruction.
Drawings
FIG. 1 is a graph showing survival rate and mortality rate of mice in each group after sham surgery or myocardial infarction;
FIG. 2 is a graph comparing the lung wet/dry weight ratio at day 28 after sham surgery or myocardial infarction in various groups of mice;
FIG. 3 is a graph comparing the serum heart failure marker type B Natriuretic Peptide (BNP) levels at day 28 after surgery for each group of mice;
FIG. 4 is a left ventricular ejection fraction and shortening fraction map of echocardiography measurements of pre-operative, post-operative day 7, day 14, and day 28 mice of each group, wherein the upper plot is the left ventricular ejection fraction map and the lower plot is the left ventricular shortening fraction map;
FIG. 5 is a typical comparison of myocardial infarction margin zone fibrosis levels (masson trichrome staining) on day 28 post-surgery for each group of mice;
FIG. 6 is a graph showing the comparison of the content of hydroxyproline, a collagen component in the myocardial infarction marginal zone on day 28 after surgery in each group of mice;
FIG. 7 is a cross-sectional area map of cardiomyocytes on day 28 after surgery for each group of mice;
FIG. 8 is a graph showing the myocardial cell death rate at day 28 after surgery for each group of mice.
Detailed Description
In order that those skilled in the art will better understand the technical solutions of the present invention to be implemented, the present invention will be further described with reference to the following specific embodiments and accompanying drawings.
The invention provides application of lactucin in preparing a medicament for preventing and treating heart failure and pathological cardiac remodeling, which comprises the following embodiments.
Example 1 use of lactucin for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling.
(1) Laboratory animal
The 12-week-old healthy male C57BL/6J mouse is provided by animal experiment center of the university of air force military medical university of people liberation force in China.
(2) Experimental Material
Lactuca sativa bitter principles (abbreviated LCP, purity > 95%) were purchased from Merck Sigma under the trade number PHL 84796; metoprolol (Metoproll, purity > 95%) was purchased from MedChemexpress under the trade designation HY-17503.
(3) Construction of animal models
Male C57BL6J mice 12 weeks old were subjected to permanent ligation of the left anterior descending branch of the coronary artery for 28 days to construct a model of heart failure and pathological heart remodeling, and the mice were randomly divided into 5 groups of 20 mice each, specifically: (1) sham control group (mice receiving Sham without coronary ligation, Sham group); (2) vehicle control group (mice receiving daily gavage vehicle from day 8 post-myocardial infarction, MI group); (3) lactucin Low dose treatment group (mice receiving daily gavage of 30mg/kg body weight/lactucin from day 8 post-myocardial infarction, MI + Low LCP group); (4) lactuca indica High dose treatment group (mice receiving daily gavage of 100mg/kg body weight/Lactuca indica daily from day 8 post-myocardial infarction, MI + High LCP group); metoprolol standardized treatment group (mice receiving 250mg/kg body weight/day Metoprolol per day from intramyocardial infarction day 8, MI + Metoprolol group), Metoprolol was the first-line clinical medication for heart failure resistance and pathological cardiac remodeling, as a positive control group.
(4) Design of experiments
After the baseline heart function of each group of mice is evaluated by an ultrasonic cardiogram before operation, the mice respectively receive a pseudo-operation or a coronary artery left anterior descending ligation operation to construct a heart stem model, the mice respectively receive a solvent, a low dose of lactucin, a high dose of lactucin and metoprolol for intragastric administration treatment every day from 8 days after the operation, the survival condition of the mice is observed every day after the operation and a survival curve is drawn, the mice receive an ultrasonic cardiogram for examination and evaluation of the heart contraction function every 7 days after the operation, the mice are killed at 28 days after the operation, the lung damp weight/dry weight ratio is measured to evaluate the degree of the pulmonary congestion, the serum heart failure marker B type natriuretic peptide (BNP) level is measured to evaluate the heart failure degree, the myocardial tissue is dyed by a masson three-color method to evaluate the myocardial infarction fibrosis degree, the myocardial infarction marginal zone tissue hydroxyproline content is measured to evaluate the collagen fiber deposition degree, the myocardial cell cross-sectional area evaluation myocardial hypertrophy level is measured, myocardial cell death was assessed by measuring myocardial cell death.
(5) The experimental results are as follows:
as shown in figure 1, Sham group mice survived within 28 days of surgery; mice in the MI group gradually died after surgery with a mortality rate of 57.9% by day 28 after surgery; the postoperative mortality rate of mice in the MI + Low LCP group was 36.8%; the postoperative mortality rate of the MI + High LCP group mice is 28.5 percent; postoperative mortality of mice in the MI + Metoproll group was 30.0%; the results show that: the experimental mice are treated by respectively adopting low and high doses of LCP and metoprolol, so that the death rate of the mice after myocardial infarction can be remarkably reduced; wherein, the effect of the high-dose LCP treatment on reducing the mortality rate after myocardial infarction is equivalent to the standardized treatment effect of metoprolol.
As shown in fig. 2, the lung wet weight/dry weight ratio of MI mice is significantly increased compared to Sham mice, which indicates that severe lung congestion is caused by heart failure, and the lung wet weight/dry weight ratio of MI + Low LCP, MI + High LCP, and MI + Metoprolol mice is significantly decreased, which indicates that the treatment can significantly reduce lung congestion caused by heart failure, wherein the effect of High-dose LCP treating to improve pulmonary congestion after myocardial infarction is equivalent to the standardized treatment effect of Metoprolol.
As shown in fig. 3, serum heart failure marker BNP levels were significantly increased in MI mice compared to Sham mice, indicating that MI caused mouse heart failure; the serum BNP of mice in the MI + Low LCP group, the MI + High LCP group and the MI + Metoproll group is obviously reduced compared with that of mice in the MI group, which shows that the treatment can obviously reduce the heart failure degree. Wherein, the effect of treating and improving the heart failure after the myocardial infarction by the high-dose LCP is equivalent to the standardized treatment effect of the metoprolol.
As shown in figure 4, after echocardiography examination, the left ventricular ejection fraction and fractional shortening of the mice in MI group are obviously reduced compared with those in Sham group, which indicates that MI causes cardiac insufficiency of the mice, and the left ventricular ejection fraction and fractional shortening of the mice in MI + Low LCP group, MI + High LCP group and MI + Methoprolol group are obviously improved compared with those in MI group, which indicates that the treatment can obviously reduce the cardiac insufficiency, wherein the effect of improving the cardiac insufficiency after myocardial infarction by the High-dose LCP treatment is equivalent to the standardized treatment effect of Metoprolol.
As shown in FIG. 5, the myocardial infarction zone of mice in MI group was significantly increased compared with those in Sham group by using masson trichrome staining, which indicates that MI causes myocardial interstitial fibrosis in mice; the fibrosis degree of the myocardial infarction marginal zone of the mice in the MI + Low LCP group, the MI + High LCP group and the MI + Metopriol group is obviously reduced compared with that of the mice in the MI group, which indicates that the treatment can obviously reduce the myocardial interstitial fibrosis; wherein the effect of the high-dose LCP on treating and improving myocardial interstitial fibrosis after myocardial infarction is equivalent to the standardized treatment effect of metoprolol.
As shown in FIG. 6, hydroxyproline was quantitatively found to be significantly increased in the myocardial infarction marginal zone of mice in the MI group compared with those in the Sham group, indicating that MI causes collagen fiber deposition in mice; the hydroxyproline content in the myocardial infarction marginal zone of the mice in the MI + Low LCP group, the MI + High LCP group and the MI + Metopriol group is obviously reduced compared with that of the mice in the MI group, which shows that the treatment can obviously reduce the collagen fiber deposition. Wherein, the effect of the high-dose LCP for treating and improving myocardial collagen fiber deposition after myocardial infarction is equivalent to the standardized treatment effect of metoprolol.
As shown in fig. 7, the measurement of the cross-sectional area of the cardiomyocytes in the MI group mice revealed a significant increase in the cross-sectional area of the cardiomyocytes in the Sham group mice, indicating that MI caused hypertrophy of the cardiomyocytes in the mice; the cross-sectional area of the cardiomyocytes in the mice with the MI + Low LCP group, the MI + High LCP group and the MI + Metoproll group is obviously reduced compared with that of the mice with the MI group, which indicates that the treatment can obviously reduce the myocardial cell hypertrophy. Wherein, the effect of treating and improving myocardial cell hypertrophy by the high-dose LCP is equivalent to the standardized treatment effect of metoprolol.
As shown in fig. 8, TUNEL staining of cardiomyocytes found a significant increase in cardiomyocyte apoptosis in the MI group mice compared to the Sham group mice, indicating that MI caused cardiomyocyte death in the mice; the myocardial cell death rate of mice in the MI + Low LCP group, the MI + High LCP group and the MI + Metoproll group is obviously reduced compared with that of mice in the MI group, which indicates that the treatment can obviously reduce the myocardial cell death. Wherein, the effect of treating and improving myocardial cell death after myocardial infarction by the high-dose LCP is equivalent to the standardized treatment effect of metoprolol.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (9)

1. Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling after myocardial infarction is disclosed.
2. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling after myocardial infarction, wherein said heart failure and pathological cardiac remodeling are animal heart failure and pathological cardiac remodeling.
3. Use of lactucin according to claim 2 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, wherein the animal is an adult C57BL/6J mouse.
4. Use of lactucin according to claim 3 in the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling after myocardial infarction, wherein the amount of lactucin in said heart failure and pathological cardiac remodeling mice is 30-100mg/kg body weight/day.
5. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, characterized in that it is used for the preparation of a medicament against cardiac insufficiency caused by heart failure and pathological cardiac remodeling.
6. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, characterized in that the lactucin is used for the preparation of a medicament against cardiomyocyte hypertrophy caused by heart failure and pathological cardiac remodeling.
7. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, wherein the lactucin is used for the preparation of a medicament against myocardial interstitial fibrosis caused by heart failure and pathological cardiac remodeling.
8. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, characterized in that the lactucin is used for the preparation of a medicament against myocardial cell death caused by heart failure and pathological cardiac remodeling.
9. Use of lactucin according to claim 1 for the preparation of a medicament for the prevention and treatment of heart failure and pathological cardiac remodeling following myocardial infarction, wherein the medicament is prepared from lactucin and an excipient.
CN202110277564.XA 2021-03-15 2021-03-15 Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling Active CN112773789B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110277564.XA CN112773789B (en) 2021-03-15 2021-03-15 Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110277564.XA CN112773789B (en) 2021-03-15 2021-03-15 Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling

Publications (2)

Publication Number Publication Date
CN112773789A CN112773789A (en) 2021-05-11
CN112773789B true CN112773789B (en) 2022-07-01

Family

ID=75762644

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110277564.XA Active CN112773789B (en) 2021-03-15 2021-03-15 Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling

Country Status (1)

Country Link
CN (1) CN112773789B (en)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
菊苣多糖对糖尿病大鼠心肌缺血再灌注过氧化的影响;李屹等;《中国老年学杂志》;20130131;第33卷;第330-331页 *

Also Published As

Publication number Publication date
CN112773789A (en) 2021-05-11

Similar Documents

Publication Publication Date Title
KR101493016B1 (en) A new use of traditional chinese medical composition
WO2023092943A1 (en) Use of dronedarone hydrochloride in combination with 5-fluorouracil in preparation of anti-tumor drug
CN102145060A (en) Dual-cordis effect of Xin Keshu
CN112773789B (en) Application of lactucin in preparing medicine for preventing and treating heart failure and pathological cardiac remodeling
CN111840112B (en) Application of carnosic acid or derivatives thereof in preparing medicine for treating diabetic complications
EA001325B1 (en) Methods ot treating or preventing interstitial cystitis
Öhman et al. Repinotan (BAY× 3702): a 5HT1A agonist in traumatically brain injured patients
CN110038002A (en) Salviandic acid A prevents and treats the purposes of muscular atrophy, myopathy and muscle skeleton complication
EP3804705B1 (en) Pharmaceutical composition for preventing diabetes and use thereof
US20040101584A1 (en) Control of cancer with annonaceous extracts
CN114712452A (en) Application of Chinese medicinal composition in preparing medicine for resisting SARS virus
CN117100733B (en) Salvianolic acid B and/or Notoginseng radix total saponin composition and its application
CN111494606B (en) New application of neuropeptide Y
WO2017194030A1 (en) Use for protein function inhibitor dapt in preparing medicine for treating endocrine diseases
CN116059292B (en) Traditional Chinese medicine composition for treating heart failure and preparation process thereof
CN115364142B (en) Application of Qihuangyi heart oral liquid in preparation of medicine for treating diabetic cardiomyopathy
CN110721310B (en) Application of pharmaceutical composition in preparation of medicine for treating acute hemorrhagic brain injury
CN115381901B (en) Pharmaceutical application of dendrobium liquid preparation
CN115243774B (en) Pharmaceutical composition containing amlodipine, chlorthalidone and amiloride
CN103172622B (en) The active isomer of silybin bis-bias succinate
CN115707466A (en) Application of captopril in preparation of medicine for treating lung allergic inflammation
CN115887502A (en) Application of parafaecalis in preparation of medicine for preventing and treating heart failure
Fernández-Codina et al. THU0570 Use of Disease-Modifying anti-Rheumatic Drugs in A Cohort of Patients with IGG4-Related Disease
CN113230340A (en) Application of kidney-tonifying asthma-preventing prescription in preparation of medicine for treating pulmonary fibrosis
CN115025103A (en) Application of tanshinone IIA sodium sulfonate in preparation of medicine

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant