CN116688082A - Application of Xinshubao tablet in preparing medicine for preventing and/or treating heart failure - Google Patents
Application of Xinshubao tablet in preparing medicine for preventing and/or treating heart failure Download PDFInfo
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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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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- 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
- A61K36/254—Acanthopanax or Eleutherococcus
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- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- 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
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
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- 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
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses an application of a heart-soothing tablet in preparing a medicine for preventing and/or treating heart failure, and animal experiments prove that the heart-soothing tablet achieves the effect of obviously preventing and treating heart failure by improving heart functions and relieving heart fibrosis. The heart-soothing tablet is applied to heart failure, and particularly has wide application prospect in preventing and treating heart failure with slightly reduced ejection fraction or ejection fraction.
Description
Technical Field
The invention particularly relates to application of a Xinshubao tablet in preparing a medicine for preventing and/or treating heart failure.
Background
Heart Failure (HF) has seen a global trend with aging population, with 2% clinical morbidity and nearly 5% annual mortality. Treatment as early as possible is decisive for improving heart failure and improving quality of life, but there is currently a lack of effective early warning markers and effective drugs for early treatment. According to the 2022 ACC/AHA/HSFA clinical diagnosis and treatment guideline, the existing 'new four-way' treatment mode medicaments are mainly targeted at blocking agents which take sodium-glucose cotransporter 2 inhibitor (SGLT 2 i) as a representative target group, and certain interaction and side effects exist in the medicament combination, so that adverse reactions of parts of patients are increased, and physical and mental health of the patients is threatened. Thus, preventing and treating the early onset and progression of heart failure is an important challenge currently faced.
The Xinshubao tablet is a medicine which is prepared by Zhangzhou PIANZAIHUANG pharmaceutical industry, is used for treating coronary heart disease, chest distress, angina caused by qi deficiency and blood stasis, hypertension, hyperlipidemia, arteriosclerosis and the like, and comprises salvia miltiorrhiza, white paeony root, radix curcumae, acanthopanax root, hawthorn fruit and the like. There is no record about early heart failure treatment in the specification examined and approved by the medicine monitoring department, and no research on the application of the heart failure treatment by using the heart comfort tablet, particularly the heart failure with slightly reduced ejection fraction or reduced ejection fraction is available at present.
Disclosure of Invention
In order to solve the problems, the invention provides application of a composition in preparing a medicament for preventing and/or treating heart failure, wherein the composition is prepared from the following raw materials in parts by weight:
100 to 300 parts of red sage root, 1000 to 3000 parts of white peony root, 150 to 450 parts of turmeric root tuber, 500 to 1500 parts of acanthopanax root and 1000 to 3000 parts of hawthorn.
Further, the medicament is a medicament for preventing and/or treating heart failure with slightly decreased ejection fraction or with decreased ejection fraction.
Further, the drug is a drug that improves cardiac function.
Still further, the drug is a drug that increases cardiac ejection fraction and short axis shortening rate.
Still further, the agent is an agent that modulates the expression of ANP and BNP factors in heart serum.
Further, the drug is a drug that reduces cardiac fibrosis.
Still further, the agent is an agent that reduces collagen fiber deposition in the heart.
Further, the drug is a drug for reducing the cardiac fibrosis-associated protein ARRB1, THBD, and further, the drug is a drug for increasing the cardiac fibrosis-associated protein FGF 1.
Further, the composition is prepared from the following raw materials in parts by weight:
200 parts of red sage root, 2000 parts of white peony root, 300 parts of turmeric root tuber, 1000 parts of acanthopanax root and 2000 parts of hawthorn.
Further, the medicine is a preparation prepared by taking the composition as an active ingredient and adding pharmaceutically acceptable auxiliary materials; the preparation is an oral preparation.
Further, the oral preparation is preferably a heart-soothing tablet.
The invention relates to heart failure with the slightly reduced ejection fraction, which is characterized by 41% -49% left heart ejection fraction.
The heart failure with the reduced ejection fraction refers to heart failure with the left heart ejection fraction less than or equal to 40 percent.
The application of the heart-soothing tablet in preparing the medicines for preventing and/or treating heart failure proves that the heart-soothing tablet achieves the obvious effect of preventing and treating heart failure by improving heart functions and relieving heart fibrosis through animal experiments. The heart-soothing tablet is applied to heart failure, and particularly has wide application prospect in preventing and treating heart failure with slightly reduced ejection fraction or ejection fraction.
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 is a graph of dynamic ejection fraction results from heart failure mice evaluated by cardiac ultrasound;
FIG. 2 is a graph of the results of cardiac ultrasound evaluation of the effect of heart comfort pads on ejection fraction of heart function in heart failure in mice;
FIG. 3 is a graph showing the effect of cardiac ultrasound on the short-axis shortening rate of heart function in heart failure in mice;
FIG. 4 is a graph showing the effect of HE staining on heart tissue morphology in mice with heart failure;
FIG. 5 is a graph showing the effect of ELISA detection of the ANP expression level of heart failure mice;
FIG. 6 is a graph showing the effect of ELISA detection of heart-soothing tablets on BNP expression level of heart failure mice;
FIG. 7 is a graph showing the effect of Masson's staining on the degree of fibrosis of heart tissue in mice with heart failure;
FIG. 8 is a graph showing the effect of Western blotting detection of the THBD expression level of heart disease heart of mice;
FIG. 9 is a graph showing the effect of Western blot detection of the heart comfort tablet on the expression level of FGF1 in heart failure of mice;
FIG. 10 is a graph showing the effect of Western blotting of the heart-soothing chips on the ARRB1 expression level of heart failure in mice.
Detailed Description
The raw materials, equipment and reagents used in the specific embodiment of the invention are all known products and are obtained by purchasing commercial products, wherein the center of the tablet is provided by Zhangzhou PIANZAIHUANG pharmaceutical industry Co., ltd, and the tablet is prepared from the following components in percentage by mass: 2000:300:1000:2000, radix salviae miltiorrhizae, radix paeoniae alba, radix curcumae, acanthopanax and hawthorn are used as raw materials.
EXAMPLE 1 application study of Xinshubao tablet for treating heart failure
1. Method of
1. Establishment and evaluation of mice model with slightly reduced ejection fraction or reduced ejection fraction for heart failure
(1) Grouping animals: 110 adult male C57BL/6J mice were randomly divided into 4 groups of 27: group 1 is a Sham group (Sham group); group 2 is a Model group (myocardial infarction Model group); group 3 was XSB-L (Model + xinshubao tablet low dose group); group 4 was XSB-H (model+Xinshubao tablet high dose group). After LAD ligation was performed on male C57BL/6N mice for 24 hours, the Sham group and the Model group were continuously perfused with pure water, the low dose group of the model+Xinshubao tablet was administered at a concentration of 0.026g/ml, the administration dose was 0.26g/kg, the high dose group of the model+Xinshubao tablet was administered at a concentration of 0.052g/ml, the administration dose was 0.52g/kg, and then the stomach was continuously perfused for 56 days (8 w) once daily.
(2) A method for modeling ejection fraction mild reduction or ejection fraction reduction heart failure: male C57BL/6J mice are fixed on an operating table after being anesthetized by intraperitoneal injection of 1% pentobarbital sodium, are intubated by trachea, and are breathed by a breathing machine with the frequency of 120 times/min, the breathing ratio of 1:1 and the tidal volume of 1.7. The left anterior limb is cut under the armpit, the chest cavity is opened between three and four ribs by using ophthalmic scissors, the anterior descending branch (LAD) of the left coronary artery of the heart is exposed, a needle is horizontally inserted from the position of 2-3 mm below the left auricle, and the chest cavity is ligated and closed.
2. Evaluation of drug efficacy of Xinshubao tablet on heart failure mice
(1) And (3) heart ultrasonic detection: after 8w heart super operation, the mice were put in 5% isoflurane anesthesia box for anesthesia, and the supine position was fixed on the operation table, and 1% isoflurane was used for maintaining anesthesia. The parasternal short axis section uses the section of the left ventricular papillary muscle level as a mark point, and records the Left Ventricular Ejection Fraction (LVEF), the left ventricular short axis shortening rate (LVFS) and the like by using an M-type ultrasonic mode. The parasternal long axis section uses the left ventricular outflow tract horizontal section as a mark point, and the B-type ultrasonic cardiogram is used for recording the wall motion image.
(2) Hematoxylin-eosin staining detects heart histomorphology changes in mice: after 8w of operation, the mice were subjected to eyeball blood collection, serum was collected by centrifugation, heart tissue samples were collected, respectively, -80 degrees of preservation and 4% paraformaldehyde fixation, and the thickness of the sections after paraffin embedding was about 6 μm. Paraffin sections were dewaxed to water. Slicing, dyeing with hematoxylin dye solution for 3-5min, washing with tap water, differentiating with differentiation solution, washing with tap water, and washing with running water. The slices are dehydrated in gradient alcohol of 85% and 95% for 5min respectively, and then are dyed in eosin dye solution for 5min. And (5) removing the water sealing piece and sealing the neutral resin sealing piece. Microscopic examination, image acquisition and analysis. When observed under a microscope, the cell nuclei are stained blue, and the cytoplasm is stained red.
(3) ELISA detection of ANP and BNP levels in mouse serum: mouse ocular vein blood was sampled, stored at room temperature for 2h, centrifuged at 2000rpm for 10min, and the supernatant was taken. Respectively setting a standard hole, a blank hole and a sample hole, adding 50ul of diluted standard substance solution into the standard hole, adding 50ul of sample diluent into the blank hole, adding 50ul of sample to be tested into the rest holes, placing into a 37-DEG oven for incubation for 60min, adding 50ul of biotin antibody working solution after removing the liquid in the holes, placing an ELISA plate film into the 37-DEG oven for incubation for 45min, removing the liquid in the holes, adding 350ul of washing solution into each hole, soaking for 2min, removing the liquid in the holes, drying on thick absorbent paper, repeating the cleaning step for 3 times, adding 100ul of enzyme conjugate working solution into each hole, and incubating for 30min in the 37-DEG oven after film covering. After removing working solution of enzyme conjugate in hole, adding 350ul of washing solution, soaking for 2min, removing washing solution in hole, taking dry, repeating the washing step 5 times, adding substrate solution 90ul in each hole, covering film, and incubating for 15min (37 deg. and light shielding). Immediately after the addition of 50ul of stop solution, the absorbance of each well was measured at 450nm using an enzyme-labeled instrument. ANP and BNP levels in mouse serum were measured in accordance with instructions using the ELISA kit of Wuhan Huamei and Elabscience, respectively.
3. Evaluation of cardiac fibrosis improving effect of Xinshubao tablet on heart failure mice
(1) Masson staining detection: conventionally dewaxing the embedded tissue slice to water, dip-dying with the prepared hematoxylin for 3min, differentiating the differentiation liquid for 3s after washing, flushing with tap water, returning to blue liquid, dip-dying with ponceau acid fuchsin dye liquid for 8min after flushing with tap water, dip-dying with aniline blue directly for 3min after soaking with phosphomolybdic acid for 3min after flushing with tap water; soaking in 1% glacial acetic acid for 1min, dehydrating, sealing, observing morphological change by using a digital slicing system panoramic scanner, and photographing.
(2) Western blot detection of mouse cardiac fibrosis protein expression: protein was extracted from the left ventricle of mice, added to 1×ripa buffer containing protease inhibitor, ground with a refiner, and centrifuged to obtain the supernatant. After concentration measurement, the extracted proteins were electrophoresed on 10% SDS-polyacrylamide gel and transferred to polyvinylidene fluoride (PVDF) membrane by an electrotransfer process. Blocking with 5% nonfat milk powder (1 XTBST) for 1h, incubating the PVDF membrane with specific antibodies (ARRB 1, FGF1 and THBD) overnight after blocking, washing with TBST, incubating with goat anti-rabbit or goat anti-mouse IgG-horseradish peroxidase (HRP) conjugated secondary antibody at room temperature for 1h, washing with TBST, and detecting with Enhanced Chemiluminescence (ECL) detection reagent.
2. Results
1. Evaluation of efficacy of Xinshubao tablet on mice with slightly reduced ejection fraction or heart failure with reduced ejection fraction
According to the 2022 ACC/AHA/HSFA clinical guidelines, LVEF-reduced heart failure (HFrEF) is defined as LVEF 40% or less; heart failure with mild reduction in LVEF (HFmrEF) is defined as lvef=41% -49%. In the process of 1-4 weeks after molding, the LVEF is found to be 41% -49%, and after 4 weeks, the heart failure characterization phenomenon that the LVEF is less than or equal to 40% is observed. The results of the dynamic process of ejection fraction of heart failure are shown in FIG. 1.
Results of heart ultrasonic examination on 8w heart failure mice show that compared with a model group, the heart-soothing tablet can raise the ejection fraction and short-axis shortening rate of the heart of the mice, wherein the ejection fraction of an XSB-L group is (47.0837 +/-4.20133)%, the short-axis shortening rate is (23.1690 +/-2.41476)% (N=5), the ejection fraction of an XSB-H group is (44.7832 +/-1.83272)%, and the short-axis shortening rate is (22.0316 +/-0.97402)% (N=6) as shown in figures 2 and 3. The morphological changes of the heart tissues of the mice are detected by hematoxylin-eosin staining, and as shown in fig. 4, compared with a Model group, the model+xinshubao tablet can reduce pathological changes such as inflammatory cell infiltration, nucleus concentration and the like of heart tissues, which indicates that the Xinshubao tablet can inhibit the necrosis of heart tissue cells. ELISA showed significantly reduced expression of ANP and BNP in the serum of mice from model+heart Shu Baogao dose group as compared to the Model group, as shown in FIGS. 5 and 6. The experimental results show that the effect of the Xinshubao at a low dosage is better than that of the Xinshubao at a high dosage, which indicates that the Xinshubao can achieve excellent effect in the dosage range (equivalent dosage for human).
In conclusion, the heart comfort tablet can raise the heart ejection fraction and short-axis shortening rate, inhibit the necrosis of heart tissue cells, regulate and control the expression of ANP and BNP factors in mouse heart serum, and has the function of improving heart.
2. Evaluation of cardiac fibrosis improving effect of Xinshubao tablet on heart failure mice
The results of the Masson staining test on the mouse hearts showed a significant decrease in collagen fiber deposition in the hearts of the Model + xinsulbao tablet high and low dose group compared to the Model group, as shown in fig. 7. The results of detection of the expression of the cardiac fibrosis proteins of the mice by western blotting are shown in figures 8, 9 and 10, compared with the Model group, the results show that the model+cardiac fibrosis related proteins ARRB1 and THBD of the mice in the high and low dose groups are obviously reduced, and the FGF1 is obviously increased, so that the cardiac fibrosis of the cardiac fibrosis tablet can be relieved.
In conclusion, the heart-soothing tablet can regulate and control protein expression of fibrosis ARRB1, FGF1 and THBD in the heart remodeling process, can reduce collagen fiber deposition, and has an anti-heart fibrosis effect.
Claims (10)
1. Use of a composition for the manufacture of a medicament for the prevention and/or treatment of heart failure, characterized in that: the composition is prepared from the following raw materials in parts by weight:
100 to 300 parts of red sage root, 1000 to 3000 parts of white peony root, 150 to 450 parts of turmeric root tuber, 500 to 1500 parts of acanthopanax root and 1000 to 3000 parts of hawthorn.
2. Use according to claim 1, characterized in that: the medicament is a medicament for preventing and/or treating heart failure with slightly reduced ejection fraction or reduced ejection fraction.
3. Use according to claim 1 or 2, characterized in that: the medicament is a medicament for improving cardiac function.
4. Use according to claim 3, characterized in that: the medicament is a medicament for increasing cardiac ejection fraction and short axis shortening rate.
5. Use according to claim 3, characterized in that: the medicament is a medicament for inhibiting the necrosis of heart tissue cells and/or regulating the expression of ANP and BNP factors in heart serum.
6. Use according to claim 1 or 2, characterized in that: the medicament is a medicament for reducing cardiac fibrosis.
7. Use according to claim 6, characterized in that: the agent is an agent that reduces collagen fiber deposition in the heart.
8. Use according to claim 6, characterized in that: the medicament is a medicament for reducing the cardiac fibrosis-associated protein ARRB1, THBD, and/or increasing the cardiac fibrosis-associated protein FGF 1.
9. Use according to claim 1, characterized in that: the composition is prepared from the following raw materials in parts by weight:
200 parts of red sage root, 2000 parts of white peony root, 300 parts of turmeric root tuber, 1000 parts of acanthopanax root and 2000 parts of hawthorn.
10. Use according to claim 1 or 2, characterized in that: the medicine is a preparation prepared by taking the composition as an active ingredient and adding pharmaceutically acceptable auxiliary materials; the preparation is an oral preparation; the oral preparation is preferably a Xinshubao tablet.
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