CN118021858A - New use of Notoginseng radix total saponin - Google Patents
New use of Notoginseng radix total saponin Download PDFInfo
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- CN118021858A CN118021858A CN202410069059.XA CN202410069059A CN118021858A CN 118021858 A CN118021858 A CN 118021858A CN 202410069059 A CN202410069059 A CN 202410069059A CN 118021858 A CN118021858 A CN 118021858A
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- heart
- lung cancer
- salvianolic acid
- heart disease
- inner diameter
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- 229930182490 saponin Natural products 0.000 title claims abstract description 22
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Classifications
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- 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
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a new application of total saponins of panax notoginseng. According to the invention, a lung cancer heart disease model experiment constructed by uratam and benzopyrene is used, and it is determined that salvianolic acid B and Panax notoginsenosides, especially salvianolic acid B combined with Panax notoginsenosides, can reduce the inner diameter of the end systole of the left ventricle and the left cardiac output, and reduce the thickness of the free wall of the right heart, the inner diameter of the end diastole of the right heart, the stroke volume of the right ventricle and the right cardiac output by increasing the ejection fraction of the left ventricle and the short axis shortening rate of the left ventricle, so that the heart function of a lung cancer heart disease mouse is improved. Under the condition that the heart function effect of a plurality of medicaments for treating heart-related diseases is poor for lung cancer heart diseases, the effect of improving the heart function of the salvianolic acid B combined with the total saponins of pseudo-ginseng is equivalent to that of the salmeterol xinafoate which is commonly used clinically at present, unexpected curative effects are obtained, and the medicament has wide application prospect.
Description
The application provides a split application of an application patent with application number 2023113872712, the application name of which is salvianolic acid B and/or total saponins of panax notoginseng composition and application thereof, and application date of which is 2023, 10 and 25.
Technical Field
The invention relates to a salvianolic acid B and/or pseudo-ginseng total saponin composition and application thereof.
Background
Heart disease is a type of disease involving the heart or blood vessels, including coronary heart disease, heart failure, cardiac hypertrophy, myocarditis, etc. Different kinds of heart disease symptoms behave differently, common symptoms are: palpitations, dyspnea, cyanosis, cough, chest pain, edema, etc., severe pulmonary edema, respiratory failure, systemic water electrolyte disorders, etc. may occur. The heart disease is mainly caused by congenital heart disease, namely heart dysplasia in fetal period, and lesions involve tissues of the heart; acquired heart disease, i.e. the postnatal heart, is caused by external or internal factors of the body. Such as: coronary atherosclerotic heart disease, rheumatic heart disease, hypertensive heart disease, pulmonary heart disease, infectious heart disease, endocrine heart disease, hematopathy heart disease, nutritional metabolic heart disease, etc.
Lung cancer is also a malignant disease, and clinical studies have now found that lung cancer is very difficult to treat in combination with heart disease. At present, two treatment schemes are adopted for patients with lung cancer combined heart diseases, one is that the common medicines for treating heart diseases in clinic, such as a cardiotonic digoxin, a heart rate improving beta receptor blocker and the like, are adopted for treating the lung cancer combined heart diseases, the patients cannot benefit from the medicines, and the ARB medicines, such as the sabatistat, with better effects on treating the lung cancer combined heart diseases, have side effects of angioedema, hypotension, renal function damage and hyperkalemia. The other is mainly tumor treatment, and research shows that cisplatin which is a representative drug of the first-generation platinum anti-tumor chemotherapeutic drug is dripped into the pericardial cavity of the heart, so that the cisplatin can obviously prevent the recurrence of malignant pericardial effusion of a lung cancer patient. However, these chemotherapeutics often have certain cardiotoxicity, which may aggravate cardiac injury itself, and cisplatin instillation also has serious problems of difficult operation, high occurrence rate of adverse events and secondary loss to patients in clinic, resulting in difficult clinical application. Other targeted drugs, such as EGFR inhibitors, are less toxic and more targeted than chemotherapeutic drugs, but studies have found that they also have significant cardiotoxicity.
The natural source plant resources are rich, the method has great excavation potential in the aspect of treating lung cancer combined heart diseases, and the effective components for treating the lung cancer combined heart diseases with little side effect and good curative effect are necessary to be searched from medicinal plants, so that the medicaments for treating the lung cancer combined heart diseases are enriched, and the lung cancer combined heart diseases are benefited.
Salvianolic acid B is active ingredient in Saviae Miltiorrhizae radix, has strong antioxidation effect, and in vivo and in vitro experiments prove that: salvianolic acid B can remove oxygen free radicals and inhibit lipid peroxidation, and is currently reported to protect heart or resist tumors; notoginseng radix total saponin is the main active substance of Notoginseng radix, has effects of inhibiting blood platelet aggregation and increasing cerebral blood flow, and is currently used for treating cerebrovascular sequelae, central retinal vein occlusion, and anterior ocular chamber hemorrhage. There is no research evidence at present that active ingredients of the red sage root and the pseudo-ginseng have a protective effect on lung cancer combined heart diseases.
Disclosure of Invention
In order to solve the problems, the invention provides application of salvianolic acid B or total saponins of panax notoginseng in preparing medicines for preventing and/or treating lung cancer heart diseases.
The invention also provides application of the salvianolic acid B combined with the pseudo-ginseng total saponins in preparing medicines for preventing and/or treating lung cancer heart diseases.
The lung cancer heart disease refers to heart disease caused by lung cancer, and comprises the condition that the existing heart disease has progressive aggravation in the lung cancer treatment process. The research of the inventor shows that the heart disease caused by lung cancer is different from the common heart disease, and the main reason is that lung cancer cells are transferred to the pericardium, so that pericardial effusion can be caused, malignant arrhythmia, heart failure and the like can be caused, the effect of treating the heart disease by adopting the traditional heart disease treatment medicine is poor, the survival time of a patient is very short, and the clinical treatment is troublesome and the curative effect is poor.
Further, the mass ratio of the salvianolic acid B to the total saponins of panax notoginseng is 120-800:30-240, preferably 200:60.
Further, the medicament has an effect of improving cardiac function of heart disease caused by lung cancer.
Still further, the medicament has the effect of increasing left ventricular ejection fraction and left ventricular short axis shortening rate, decreasing left ventricular end systole inner diameter and left cardiac output.
Still further, the medicament has the effect of reducing the thickness of the free wall of the right heart, the inner diameter of the end diastole, the stroke volume of the right ventricle and the right cardiac output.
Further, the medicine is a medicine for preventing and treating heart failure caused by lung cancer.
The invention also provides a combined medicament for preventing and/or treating lung cancer heart disease, which is used for simultaneously or respectively administering salvianolic acid B and total saponins of pseudo-ginseng; the active ingredients of the combination medicine consist of salvianolic acid B and total saponins of pseudo-ginseng.
Further, the mass ratio of the salvianolic acid B to the total saponins of panax notoginseng is 120-800:30-240, preferably 200:60.
The invention finally provides a composition for preventing and/or treating lung cancer heart disease, wherein the active ingredients of the composition consist of salvianolic acid B and total saponins of panax notoginseng; the composition is a preparation prepared by adding pharmaceutically acceptable auxiliary materials into the active ingredients.
Further, the mass ratio of the salvianolic acid B to the total saponins of panax notoginseng is 120-800:30-240, preferably 200:60.
The invention relates to application of salvianolic acid B and/or total arasaponin in preparing medicines for preventing and/or treating lung cancer heart diseases, and a lung cancer heart disease model experiment constructed by uratein and benzopyrene is used for determining that the salvianolic acid B and the total arasaponin, especially the salvianolic acid B combined with the total arasaponin, reduce the inner diameter of the end systole and the output of the left heart by increasing the ejection fraction of the left heart chamber and the short axis shortening rate of the left heart chamber, and reduce the thickness of the free wall of the right heart, the inner diameter of the end diastole of the right heart, the output of the right heart chamber and the output of the right heart, thereby improving the heart function of a lung cancer heart disease mouse. Under the condition that the heart function effect of a plurality of medicaments for treating heart-related diseases is poor for lung cancer heart diseases, the effect of improving the heart function of the salvianolic acid B combined with the total saponins of pseudo-ginseng is equivalent to that of the salmeterol xinafoate which is commonly used clinically at present, unexpected curative effects are obtained, and the medicament has wide application prospect.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
Fig. 1 study roadmap.
Detailed Description
The materials, equipment and reagents used in the specific embodiments of the invention are all known products and are obtained by purchasing commercially available products.
Example 1 use of Danshen root and Sanchi monomer components in treating Lung cancer heart disease
1. Experimental reagent
Uratam (sigma company of united states); benzopyrene (Shanghai Yuan leaf Biotechnology Co., ltd.); salvianolic acid B (Shanghai Michelson Biochemical technologies Co., ltd.); notoginseng radix total saponin (Shanghai Yuan Yes Biotechnology Co., ltd.); sha Kuba Tremella, sartan (Beijing Norhua pharmaceutical Co., ltd.); digoxin tablets (dubeide noro pharmaceutical company limited); metoprolol succinate tablet (ex aslicon pharmaceutical Co.); normal saline (limited pharmaceutical industry of sichuan sciences).
2. Experimental animals and groups
Experimental grouping: SPF-class Balb/c mice of 8 weeks old were purchased from animal experiments center in Guangdong province, 120 in total, and divided into 8 groups of 15 each, respectively: 1. blank control group; 2. a model group; 3. salvianolic acid B (200 mg/kg); 4. notoginseng radix total saponins (60 mg/kg); 5. salvianolic acid B+Notoginseng radix total saponins group (200 mg/kg+60 mg/kg); 6. sha Kuba triptan group (60 mg/kg); 7. digoxin group (oral 0.1 mg/kg); 8. metoprolol succinate (oral 20 mg/kg).
3. Experimental equipment
Ultrapure water machine (feidi biotechnology limited, guangzhou); electronic balance (German BP 2215); high resolution small animal ultrasound imaging systems (visualsonic corporation, canada).
4. Experimental method
4.1 Preparation of a model of heart disease in mice lung cancer
SPF-class Balb/c mice are fed in an SPF-class environment with the temperature of 20-26 ℃ and the relative humidity of 40-70% and the brightness of 12/12 hours alternately, so that the mice can drink and ingest freely. The urapidan solution (physiological saline as solvent) and the benzopyrene solution (corn oil as solvent) were administered by intraperitoneal injection at a dose of 1g/kg, 1 time per week for 4 weeks, and the benzopyrene solution was infused at a dose of 50mg/kg (i.g.), 2 times per week for 8 weeks. Control mice were given equal amounts of saline and corn oil in the same manner and time. The number of lung tumors was counted 10 weeks after administration, the lung tumor size was measured and the heart function was examined to evaluate whether the lung cancer heart disease mouse model was successfully constructed. Research evidence shows that the modeling success rate of the method is 100%.
4.2 Administration of drugs
Administration: salvianolic acid B (200 mg/kg), panax notoginseng saponins (60 mg/kg), salvianolic acid B+Panax notoginseng saponins (200 mg/kg+60 mg/kg) mice were continuously given with the corresponding doses of the drugs by gavage after the last administration of urapidan, positive drug group mice were continuously given with the drugs by gavage after the last administration of urapidan by 60mg/kg of Sha Kuba troxalines, digoxin groups were continuously given with the drugs by gavage after the last administration of urapidan by 0.1mg/kg of digoxin tablets, and metoprolol succinate groups were continuously given by gavage after the last administration of urapidan by 20mg/kg of metoprolol succinate for 10 weeks.
Mice in the blank group and the model group were subjected to gastric lavage with an equal volume of physiological saline and continuous gastric lavage administration was performed for 10 weeks.
After the end of the administration, 10 subsequent experiments were performed per group.
4.3 Echocardiography to detect changes in cardiovascular function in mice:
the cardiovascular function of mice was measured with a model Vevo3100 high resolution small animal ultrasound imaging system manufactured by visual sonic company, canada. After the mice were anesthetized with 1% isoflurane, the hairs in front of the chest of the mice were removed, and the chest of the mice was applied with an ultrasonic couplant, and the right heart function (right heart free wall thickness (RVWT), right end diastole inner diameter (RVID; d), right Ventricular Stroke Volume (RVSV), right cardiac output (RVCO), and left heart function (left ventricular Ejection Fraction (EF), left ventricular short axis shortening rate (FS), left ventricular end systole inner diameter (LVID; s), left cardiac stroke volume (LVSV), left cardiac output (LVCO)) of the mice were examined.
4.4 Calculation of tumor number and volume in lung tissue of mice:
immediately after the end of the cardiac function test, each group of mice was sacrificed, the whole lung tissue was isolated, and the number of tumors (lung cancer tumor node number) and tumor volume in the lung tissue were detected.
4.5 Data processing
All data were statistically analyzed using SPSS 24.0. Data are expressed in mean+ -SD, t-test analysis is adopted between two groups of data, ANOVA single-factor analysis of variance is adopted between each group, and P is less than or equal to 0.05, so that significant difference is considered.
4.6 Study of technical routes:
See in particular fig. 1.
4.7 Experimental results:
4.7.1 influence of Danshen root and Notoginseng radix monomer components on left heart function of mice with heart disease caused by lung cancer
The results are shown in Table 1: after the model is made by uratam and benzopyrene, the left heart function of the model group mice is obviously damaged, which is reflected in that: the left ventricular ejection fraction (EF%) and the left ventricular short axis shortening rate (FS%) are obviously reduced (P < 0.01), the left ventricular end-systole inner diameter (LVID; s) (P < 0.01) and the left cardiac output (LVCO) are obviously increased (P < 0.05); after being treated by the salvianolic acid B, the total arasaponin and Sha Kuba trovaptan respectively, the left heart function of the mice is improved, which is reflected in: the left ventricular ejection fraction (EF%) and the left ventricular short axis shortening rate (FS%) are obviously increased (P is less than 0.01), the left ventricular end-systole inner diameter (LVID; s) (P is less than 0.01) and the left cardiac output (LVCO) (P is less than 0.05) are obviously reduced, and the treatment effect of the salvianolic acid B+the panax notoginseng saponins is better than that of the salvianolic acid B and the panax notoginseng saponins which are singly administered. The evidence shows that the salvianolic acid B and the panax notoginseng saponins can improve the left heart function of mice with lung cancer heart diseases, and the combined administration effect is better.
Table 1: left heart function of mice
Note that: ** P < 0.01 compared with the blank control group; ## P < 0.01 compared to model group.
4.7.2 Influence of Danshen root and Notoginseng radix monomer components on right heart function of mice with heart disease caused by lung cancer
The results are shown in Table 2: after the model is made by uratam and benzopyrene, the right heart function of the model group mice is obviously damaged, which is reflected in that: right heart free wall thickness (RVWT) (P < 0.05), right end diastole inner diameter (RVID; d), right ventricular stroke volume (RV SV) (P < 0.05), and right cardiac output (RV CO) are significantly increased (P < 0.01); after being treated by the salvianolic acid B, the total arasaponin and Sha Kuba trovaptan respectively, the right heart function of the mice is improved, which is reflected in: right heart free wall thickness (RVWT) (P < 0.05), right end diastole inner diameter (RVID; d) (P < 0.01), right ventricular stroke volume (RV SV) (P < 0.05), and right cardiac output (RV CO) are significantly reduced (P < 0.05). And the treatment effect of the salvianolic acid B plus the total arasaponin is better than that of the single administration of the salvianolic acid B and the total arasaponin. The evidence shows that the salvianolic acid B and the panax notoginseng saponins can improve the right heart function of mice with lung cancer heart diseases, and the combined administration effect is better.
Table 2: right heart function of mice
Note that: *P＜0.05,** P < 0.01 compared with the blank control group; #P＜0.05,## P < 0.01 compared to model group.
Influence of 4.7.3 Danshen root and Notoginseng radix monomer components on lung cancer heart disease mouse tumor
As shown in Table 3, after modeling with Ulatin+benzopyrene, a large number of tumors (P < 0.01) could be detected in the lung tissue of the mice in the model group, suggesting that the lung cancer heart disease model was successfully constructed. After treatment with salvianolic acid B, total saponins of panax notoginseng, sha Kuba trovaptan, digoxin and metoprolol succinate, the number of tumors and the volume of tumors in the lung tissue of the mice are not obviously changed (P is more than 0.05), and the result suggests that: salvianolic acid B, notoginseng radix total saponin, sha Kuba troxatan, digoxin and metoprolol succinate have no effect on lung cancer.
Table 3: number of tumors and tumor volume in mouse lung tissue
Note that: ** P < 0.01 compared with the blank group.
The results highly suggest that the salvianolic acid B and the panax notoginseng saponins can improve the heart function of mice with lung cancer heart disease, have better combined use effect, have no treatment effect on lung cancer, and mainly play a role in improving the heart function of the mice with lung cancer heart disease through the cardioprotection effect.
5. Discussion of the invention
As lung cancer progresses, the human body suffers from different degrees of organ failure, with heart damage being the most clinically interesting problem: the lung cancer can cause damage to the heart in the occurrence and development process, serious arrhythmia and abnormal electrophysiological conduction of the heart, and the heart is enlarged, and finally heart failure is caused. Heart failure can cause the patient to feel hypoxia, chest distress, suffocation and dyspnea, and lung cancer itself can also cause reduced respiratory function. If the disease progress of heart failure caused by lung cancer is not controlled, chest water and large-volume lung occupation are generated, ventilation is influenced, dyspnea is serious, and then respiratory failure is developed, so that if heart failure occurs to a patient suffering from lung cancer, the condition is often indicated to enter the final stage, and the life cycle is greatly shortened. Early experiments also show that the effect of improving cardiac function can be achieved by proportionally and jointly reducing half dose, so that the salvianolic acid B and the total saponins of pseudo-ginseng are jointly applied to preventing and treating lung cancer heart diseases, and the method has clinical popularization and application prospects.
Claims (4)
1. Use of Notoginseng radix total saponin in preparing medicine for preventing and/or treating heart disease caused by lung cancer is provided.
2. Use according to claim 1, characterized in that: the medicine has effects of improving heart function of heart disease caused by lung cancer.
3. Use according to claim 2, characterized in that: the medicine has the effects of increasing left ventricular ejection fraction and short left ventricular short axis shortening rate, reducing left ventricular end systole inner diameter and left cardiac output, and reducing right heart free wall thickness, right end diastole inner diameter, right ventricular stroke volume and right cardiac output.
4. Use according to claim 3, characterized in that: the medicine is used for preventing and treating heart failure caused by lung cancer.
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