CN108904492B - Pharmaceutical composition for treating pulmonary heart disease - Google Patents
Pharmaceutical composition for treating pulmonary heart disease Download PDFInfo
- Publication number
- CN108904492B CN108904492B CN201810641752.4A CN201810641752A CN108904492B CN 108904492 B CN108904492 B CN 108904492B CN 201810641752 A CN201810641752 A CN 201810641752A CN 108904492 B CN108904492 B CN 108904492B
- Authority
- CN
- China
- Prior art keywords
- ethanol
- pharmaceutical composition
- weight
- heart disease
- treating
- 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
Links
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
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a pharmaceutical composition for treating pulmonary heart disease, which comprises 15-70 parts by weight of dihydroquercetin, 30-80 parts by weight of procyanidin and 10-30 parts by weight of phytolaccagenin A, and an application of the pharmaceutical composition in treating pulmonary heart disease. The three compounds have wide sources and are convenient to obtain, so that the three compounds have high development potential when being developed into related products such as food additives, health-care foods, medicines and the like.
Description
Technical Field
The invention relates to a pharmaceutical composition for treating pulmonary heart disease and application thereof, belonging to the technical field of natural pharmaceutical chemistry.
Background
Pulmonary heart disease (abbreviated as cor pulmonale) is a heart disease in which the pulmonary circulation resistance is increased and pulmonary hypertension is increased due to chronic lesions of the lung, thoracic cage or pulmonary artery, which in turn causes the right ventricle to be hypertrophic, enlarged or even the right heart to be exhausted. The disease course is long, the disease condition is critical, and the morbidity and the mortality are high so far. The clinical treatment of chronic pulmonary heart disease patients is difficult due to the pathophysiological characteristics of the chronic pulmonary heart disease patients when the chronic pulmonary heart disease patients have heart failure, the heart failure resistance treatment is still performed on the basis of relieving hypoxia and carbon dioxide retention and correcting acid-base balance and electrolyte disturbance at present, the heart failure resistance treatment comprises the application of cardiotonic, diuretic and vasodilator, but the patients have hypoxia and respiratory failure, poor tolerance to the cardiotonic, and the diuretic is easy to cause the problems of electrolyte disturbance, blood concentration, thick sputum and the like, and is not favorable for long-time treatment.
At present, western medicines can only be used for symptomatic medicine in the aspect of preventing and treating the pulmonary heart disease and cannot play a role in preventing and treating the pulmonary heart disease, and the pharmaceutical composition has the characteristics of synergistic effect and the like due to the interaction of the components, so that the pharmaceutical composition has great advantages in the aspect of preventing and treating the pulmonary heart disease, and therefore, a pharmaceutical composition which has the function of reducing inflammatory response and can achieve the effects of preventing and treating the pulmonary heart disease and the application thereof are urgently needed.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects of the prior art and provide the pharmaceutical composition for treating the pulmonary heart disease, which has good prevention and treatment effects and sufficient raw material supply.
In order to solve the technical problems, the invention provides a pharmaceutical composition for treating pulmonary heart disease, which comprises 15-70 parts by weight of dihydroquercetin, 30-80 parts by weight of procyanidine and 10-30 parts by weight of phytolaccagol A.
The weight parts of the dihydroquercetin and the procyanidin are 55-65, 35-45 and 15-20 respectively.
The composition can be made into one or more of solution, tablet, capsule and pill.
The composition also comprises auxiliary agents within a pharmaceutically allowable range, wherein the auxiliary agents are one or more of emulsifying agents, solubilizing agents, excipients or stabilizing agents.
The preparation method of the phytolaccagenin A comprises the following steps: taking a proper amount of American pokeberry seeds, drying to constant weight, crushing, adding 70-95% ethanol, performing hot reflux extraction for at least 2 times, wherein the addition amount of the ethanol is 10-20 times of the dry weight of the medicinal materials, merging extracting solutions, concentrating to 1/10-1/5 of the dry weight of the medicinal materials, filtering, subjecting filtrate to nonpolar macroporous adsorption resin, performing static adsorption for at least 4 hours, washing with water for at least 10 column volumes, eluting with 10-20% ethanol for at least 6 column volumes, eluting with 40-50% ethanol for 3-5 column volumes, eluting with 70-80% ethanol for 5-7 column volumes, collecting 70-80% ethanol eluate, concentrating until no alcohol smell exists, filtering, collecting filtrate to obtain a column solution, and using a nonpolar organic solvent with a volume ratio of (2-1): 1: after the column solution is extracted for at least 2 times, the water layer is extracted with (3-1) a weak polar organic solvent with the volume ratio of 1: and (3) extracting the solution for 2-3 times, combining the weak-polarity organic solvents, concentrating, drying, crushing the dried product, adding the composite solvent for recrystallization, collecting crystals, and drying to obtain the phytolaccagenin A.
The nonpolar macroporous adsorption resin comprises D101, HPD-100, ADS-8 or X-5.
The non-polar organic solvent comprises petroleum ether, and the weak-polar organic solvent comprises acetone, ethyl acetate or chloroform. The recrystallization method of the dried substance comprises the following steps: dissolving the dried substance with acetic acid in an amount which is 2-3 parts by volume of the dried substance, centrifuging, preserving the heat of the supernatant at 40-50 ℃, dropwise adding methanol or ethanol under the condition of stirring, wherein the adding amount of the methanol or the ethanol is 8-10 times of that of the acetic acid, continuously dropwise adding triethylamine under the condition of preserving the heat and stirring after the methanol or the ethanol is added, wherein the adding amount of the triethylamine is 0.5-1.5 times of that of the acetic acid, cooling at room temperature, refrigerating in a 0 ℃ refrigerator overnight, taking out the product the next day, filtering, washing with water for crystallizing for at least 2 times, collecting crystals, and drying.
The application of the pharmaceutical composition in treating pulmonary heart disease.
The pharmaceutical composition is used for being combined with an anti-heart failure drug to improve the treatment effect of heart failure caused by pulmonary heart disease.
The qualitative identification method of the phytolaccagenin A comprises the following steps: 2mg of the phytolaccagenin A standard substance is taken and dissolved in 10mL of ethyl acetate to be used as a reference substance solution for standby. Taking 2mg of the prepared phytolaccagenin A crystal, adding 10mL of ethyl acetate for dissolving, and using as a test solution for standby.
Taking a TLC plate with the specification of 10cm × 10cm, respectively taking the reference substance solution and the test solution, drying, putting the TLC plate into a development cylinder for development, wherein the development solution is a mixed solution of chloroform and methanol, the ratio of 8: 2, taking the TLC plate out after the mixed solution runs to the front edge of the TLC plate, drying, spraying concentrated sulfuric acid-vanillin color developing agent, drying at high temperature until the color is developed, marking the position of the color development point, recording the position of the front edge of the TLC plate solvent, obtaining through tests that the reference substance solution and the test solution have color development points at the same height, and the test solution has no other miscellaneous points, calculating the Rf value of the color development point to be 0.57, and confirming that the test solution contains high-content of the metapokeberry phenol A monomer.
Dihydroquercetin exists in various plants as an important flavonoid compound, and has high content in Larix Gmelini, especially Douglas fir. In recent years, the presence of dihydroquercetin has also been found in fruits, particularly grapes, oranges and grapefruit. Dihydroquercetin has many important biologically active functions, including: 1. and (3) anticancer: has activity on murine leukemia P388, and the life prolongation rates of 150 mg/kg and 100mg/kg are 40% and 37%, respectively. 2. And (3) antibiosis: has strong bacteriostatic action on staphylococcus aureus, colon bacillus, dysentery bacillus and typhoid bacillus. 3. Various enzymes are inhibited and activated to produce different physiological effects, such as inhibition of proliferation of common lymphocytes. 4. Antioxidant activity, protecting mitochondria from damage by peroxidized groups without affecting enzyme activity. 5. Protecting erythrocyte, and preventing oxidative hemolysis.
Procyanidine is called OPC for short, is a bioflavonoid with a special molecular structure, is a novel high-efficiency antioxidant, has the function of enhancing immunity and has strong in-vivo activity. Experiments prove that the anti-free radical oxidation capacity of the OPC is 50 times of that of vitamin E and 20 times of that of vitamin C, the OPC is quickly and completely absorbed, the maximum blood concentration can be reached after the OPC is orally taken for 20 minutes, and the metabolism half-life period is 7 hours.
The phytolaccagenol A (American ginseng A) medicinal material base source is seeds of phytolacca americana (Phytolacca americana) of Phytolacca, wherein the yield of the phytolaccagenol A is up to 0.013%, and the biological activity of the phytolaccagenol A is antioxidant activity, remarkably inhibits copper-induced low-density lipoprotein oxidation, and is in a dosage-dependent manner.
Dihydroquercetin, procyanidine and phytolaccagenin A all have strong antioxidant activity, but the functions of dihydroquercetin, procyanidine and phytolaccagenin A in the adjuvant therapy of pulmonary heart disease are not reported.
The invention achieves the following beneficial effects:
the research result of a monocrotaline-induced rat pulmonary heart disease model shows that after the composition is administered, pulmonary artery pressure of a model rat is reduced, and IL-8 and TNF- α contents in serum, alveoli and tissues are reduced, which suggests that the composition can reduce airway inflammatory response, relieve inflammation and injury and prevent pulmonary heart disease by reducing the contents of IL-8 and TNF- α.
The observation result of the clinical curative effect of the chronic pulmonary heart disease with heart failure shows that the composition of the invention can obviously relieve the clinical symptoms of patients and the evaluation index of the cardiopulmonary function when being used for treating the chronic pulmonary heart disease by combining on the basis of the conventional heart failure resistant medicament.
Therefore, the composition provided by the invention has the effect of reducing inflammatory response and can achieve the effect of preventing and treating the pulmonary heart disease. And the three compounds have wide sources and are convenient to obtain, so that the three compounds have high development potential when being developed into related products such as food additives, health-care foods, medicines and the like.
Detailed Description
The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby.
The first embodiment is as follows:
the weight portion of the dihydroquercetin is 55, the weight portion of the procyanidin is 45, the weight portion of the phytolaccagenin A is 15, and the dihydroquercetin, the procyanidin and the phytolaccagenin A are prepared into oral solution under the condition of an emulsifier.
Dihydroquercetin and procyanidin are both commercially available products.
The preparation method of the phytolaccagenin A comprises the following steps: taking a proper amount of American pokeberry seeds, drying to constant weight, crushing, adding 70% ethanol, carrying out hot reflux extraction for 2 times, wherein the adding amount of the ethanol is 10 times of the dry weight of the medicinal materials, merging extracting solutions, concentrating to 1/10 of the dry weight of the medicinal materials, filtering, subjecting filtrate to D101 macroporous adsorption resin, statically adsorbing for 4 hours, washing 10 column volumes with water, eluting 6 column volumes with 10% ethanol, eluting 3 column volumes with 40% ethanol, eluting 5 column volumes with 70% ethanol, collecting 70% ethanol eluate, concentrating until no alcohol smell exists, filtering, collecting filtrate to obtain a column solution, and using petroleum ether with a volume ratio of 2: 1: after 2 extractions of the column solution, the aqueous layer was further extracted with 3:1 volume ratio of acetone: extracting with column solution for 2 times, mixing acetone extractive solutions, concentrating, drying, pulverizing, adding composite solvent, recrystallizing, collecting crystal, and drying to obtain phytolaccagenin A.
The recrystallization method of the dried substance comprises the following steps: dissolving the dried substance with acetic acid of 2 parts by volume equivalent to the weight of the dried substance, centrifuging, preserving the temperature of supernatant fluid at 40 ℃, dropwise adding methanol under the condition of stirring, wherein the adding amount of the methanol is 8 times of that of the acetic acid, continuously dropwise adding triethylamine under the condition of preserving the temperature and stirring after the methanol is added, wherein the adding amount of the triethylamine is 0.5 times of that of the acetic acid, cooling at room temperature, putting the cooled triethylamine into a 0 ℃ refrigerator for refrigerating overnight, taking out the cooled triethylamine after the next day, filtering, washing with water for 2 times, collecting crystals and drying.
Example two
The weight portion of the dihydroquercetin is 65, the weight portion of the procyanidine is 35, the weight portion of the phytolaccagenin A is 20, and the dihydroquercetin, the procyanidine and the phytolaccagenin A are mixed with auxiliary materials and then tabletted to prepare tablets.
Dihydroquercetin and procyanidin are both commercially available products.
The preparation method of the phytolaccagenin A comprises the following steps: taking a proper amount of American pokeberry seeds, drying to constant weight, crushing, adding 95% ethanol, carrying out hot reflux extraction for 3 times, wherein the addition amount of the ethanol is 20 times of the dry weight of the medicinal materials, merging extracting solutions, concentrating to 1/5 of the dry weight of the medicinal materials, filtering, subjecting filtrate to HPD-100 macroporous adsorption resin, carrying out static adsorption for 5 hours, washing 12 column volumes with water, eluting 8 column volumes with 20% ethanol, eluting 5 column volumes with 50% ethanol, eluting 7 column volumes with 80% ethanol, collecting 80% ethanol eluate, concentrating until no alcohol smell exists, filtering, collecting filtrate to obtain a column solution, and using petroleum ether with the volume ratio of 1: after 3 times of extraction of the column solution, the aqueous layer was further extracted with ethyl acetate at a 1:1 volume ratio: extracting with column solution for 3 times, mixing ethyl acetate extractive solutions, concentrating, drying, pulverizing, adding composite solvent, recrystallizing, collecting crystal, and drying to obtain phytolaccagenin A.
The recrystallization method of the dried substance comprises the following steps: dissolving the dried substance with acetic acid of which the volume is 3 parts of the weight of the dried substance, centrifuging, keeping the temperature of supernatant at 50 ℃, dropwise adding ethanol under the condition of stirring, wherein the addition amount of the ethanol is 10 times of that of the acetic acid, continuously dropwise adding triethylamine under the condition of keeping the temperature and stirring after the addition of the ethanol is finished, wherein the addition amount of the triethylamine is 1.5 times of that of the acetic acid, cooling at room temperature, putting the cooled dried substance into a 0 ℃ refrigerator for refrigerating overnight, taking out the cooled substance the next day, filtering, washing with water for 3 times, collecting crystals, and drying.
Example three:
the present embodiment is different from the first embodiment only in that: the capsule is prepared by mixing dihydroquercetin, procyanidin and phytolaccagol A with adjuvants, and making into capsule, wherein the weight parts of dihydroquercetin, procyanidin and phytolaccagol A are 15, 80 and 10 respectively.
Example four:
the present embodiment is different from the second embodiment only in that: the weight portion of the dihydroquercetin is 70, the weight portion of the procyanidine is 30, the weight portion of the phytolaccagenin A is 30, and the dihydroquercetin, the procyanidine and the phytolaccagenin A are mixed with auxiliary materials to prepare pills.
The pharmaceutical composition is prepared into dosage forms such as tablets, capsules, pills and the like, and can also be prepared into solution, and the drug effect of the pharmaceutical composition is verified through the following drug effect tests.
Experimental example of drug action:
first, the composition of the invention has the effect on the rat pulmonary heart disease model caused by monocrotaline
1. Drugs and reagents
MCT (monocrotaline), available from Sigma company, usa;
IL-8, TNF- α radioimmunoassay from R & D Systems, Inc.;
the composition of the present invention, the composition of example one.
2. Experimental methods
30 SD rats are randomly divided into 3 groups, a blank control group, a model control group and a composition group, 10 SD rats are in each group, the male and female rats are half in each group, except the blank control group, MCT50mg/kg is uniformly injected into the abdominal cavity for one time, and a pulmonary heart disease model is formed after 28 days. And (3) starting gastric perfusion administration while molding, wherein the composition group is administered with 0.2g/kg of the composition 1 time per day, and simultaneously the blank control group and the model control group are infused with physiological saline with equal volume, and after 28 days, all indexes are detected.
Right heart catheterization measures pulmonary artery pressure in each group of rats. After anesthetizing the rats by intraperitoneal injection of 20g/L pentobarbital at 10mL/kg, a longitudinal incision with the length of about 1.5cm is made in the middle of the neck, the right external jugular vein is dissociated by about 1cm, ligation and cut are carried out, and a polyethylene tube (with the outer diameter of 0.9mm and the inner diameter of 0.6mm) filled with heparin solution is inserted into the right ventricle and the pulmonary artery through the jugular vein. The position of the catheter tip is judged according to the pressure curve waveform shown by the monitor, and the pulmonary artery pressure is recorded by a multi-lead physiological recorder.
Collecting blood from femoral vein after pulmonary artery pressure detection, separating serum, performing left lung bronchus alveolar lavage by opening chest, centrifuging to obtain supernatant, collecting right lung tissue, homogenizing, centrifuging to obtain supernatant, and measuring IL-8 and TNF- α in serum, alveolar lavage fluid (BALF) and lung homogenate supernatant.
2. Results
The result shows that the pulmonary artery pressure of the model group is obviously increased (P is less than 0.01) after the model is manufactured compared with the blank control group, which indicates that the model is successfully manufactured; compared with the model group, the pulmonary arterial pressure of the composition group is reduced after administration (P is less than 0.05), and the experimental result shows that the composition can effectively reduce the pulmonary arterial pressure caused by MCT, which is shown in Table 1.
Table 1 effect of composition on pulmonary artery pressure in rat pulmonary heart disease model (x ± s, n ═ 10)
P <0.01 compared to blank; in comparison with the set of models,#P＜0.05。
compared with the blank control group, the model group rats have obviously increased IL-8 and TNF- α levels (P is less than 0.01) in serum, BALF and lung tissue homogenate, and compared with the model control group, the IL-8 and TNF- α levels of the composition group of the invention are both reduced (P is less than 0.01, P is less than 0.05), and the results are shown in tables 2 and 3.
TABLE 2 Effect of the compositions on IL-6 in rat cor pulmonale model serum, BALF, lung homogenate (x. + -.s, n ═ 10)
P <0.01 compared to blank; in comparison with the set of models,#P＜0.05，##P＜0.01。
TABLE 3 Effect of the compositions on TNF- α in rat cor pulmonale model serum, BALF, lung homogenate (x. + -. s, n ═ 10)
P <0.01 compared to blank; in comparison with the set of models,#P＜0.05，##P＜0.01。
the research result shows that after the composition is administered, pulmonary artery pressure of a model rat is reduced, and IL-8 and TNF- α contents in serum, alveoli and tissues are reduced, which indicates that the composition can reduce the airway inflammatory response, relieve inflammation and injury and prevent the occurrence of pulmonary heart disease by reducing the IL-8 and TNF- α contents.
Second, composition for chronic pulmonary heart disease with heart failure clinical efficacy observation
1. Experimental methods
1.1 the data source selects 86 cases of patients with chronic pulmonary heart disease and heart failure, and the diagnosis of all cases accords with the diagnosis standard of the pulmonary heart disease, but not includes the standard of (1) acute and chronic left cardiac insufficiency, acute myocardial infarction, acute coronary syndrome, acute pulmonary embolism, primary pulmonary hypertension, tuberculosis, pulmonary interstitial fibrosis and the like. (2) Malignant tumor, liver and kidney function insufficiency and the like which may affect the disease evaluation. (3) The study protocol was not completed. The control group and the treatment group were randomly divided. Among 86 patients, 48 men and 38 women; the age was 50-78 years, the mean (63.10 + -10.30) years, and the treatment group and the control group were randomly divided into 43 cases. The difference between the two data sets was not statistically significant (P > 0.05).
1.2 the treatment method comprises the steps of applying oxygen inhalation to a control group, applying antibiotics to resist infection, relieving bronchospasm, reducing phlegm, dredging respiratory tract and the like to improve respiratory function, applying cedilan to strengthen heart, applying a proper diuretic to control heart failure, applying a vasodilator to improve circulation and the like, and applying 0.5 g/day of the composition to the treatment group on the basis. The two treatment courses are 2 weeks.
1.3 evaluation index
1.3.1 signs of symptoms are significant: dyspnea, cyanosis, edema and cervical vein anger symptoms are obviously relieved, dry and damp rales of the lung disappear or are obviously reduced, the palpated liver under the rib is reduced by 2cm, and the cardiac function reaches more than grade 2; the method has the following advantages: dyspnea, cyanosis, edema and cervical vein anger symptoms are improved, dry and damp rales of the lung are improved, palpated liver under the rib is reduced by 1cm, and cardiac function reaches more than grade 3; and (4) invalidation: edema does not subside obviously, liver does not retract, the anger of the jugular vein is not relieved, the cardiac function is not improved, and symptoms are not improved obviously or aggravated and die.
1.3.2 blood gas analysis values of arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaO2) and blood oxygen saturation (SaO2) before and after treatment of two groups of patients were measured using a blood gas analyzer.
1.3.3 Heart color ultrasound measurement of mean pulmonary artery pressure (mPAP), Left Ventricular Ejection Fraction (LVEF) changes.
2. Results of the experiment
2.1 clinical Observation of therapeutic Effect
The total effective rate of the patients in the treatment group is 93.5 percent, which is higher than that of the patients in the control group by 85.0 percent, the difference has statistical significance (P is less than 0.05), and the results are shown in a table 4.
TABLE 4 Observation of clinical efficacy (%) of two groups of patients
P <0.05 compared to control.
2.2 two groups of patients PaO2、PaCO2、SaO2Comparative blood gas analysis showed that two groups of pre-treatment PaO2、PaCO2、SaO2No statistical significance (P > 0.05); post-treatment two groups of PaO2、SaO2The mean water level was higher (P <0.05) than that before treatment in the same group, wherein the treatment group PaO2The increase is obvious compared with the control group (P < 0.05). PaCO2The ratio of the total amount of the components is reduced compared with that of the same group before treatment (P is less than 0.05), and the ratio of the treated group to the control group is obviously reduced (P is less than 0.05), and the results are shown in Table 5.
TABLE 5 two groups of patients PaO2、PaCO2、SaO2Numerical comparison (x + -s)
P <0.05 compared to the group before treatment; compared with the control group, the compound of the formula,#P＜0.05。
the comparison of mPA and LVEF on heart color ultrasound results of the patients in the 2.32 groups shows that the mPA and LVEF levels of the patients in the treatment group are better than those in the control group (P is less than 0.05), and the results are shown in Table 6.
TABLE 6 comparison of mPAP and LVEF for two groups of patients (x. + -. s)
P <0.05 compared to the group before treatment; compared with the control group, the compound of the formula,#P＜0.05。
therefore, on the basis of the conventional anti-heart failure medicine, the composition of the invention is used for treating chronic pulmonary heart disease, can obviously relieve the clinical symptoms of patients and the evaluation index of cardiopulmonary function, and has obviously better effect than that of a control group. Has no anaphylaxis, fatal arrhythmia, liver and kidney damage during the treatment period.
The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.
Claims (7)
1. A pharmaceutical composition for treating pulmonary heart disease, which is characterized in that: the pharmaceutical composition comprises 15-70 parts by weight of dihydroquercetin, 30-80 parts by weight of procyanidine and 10-30 parts by weight of phytolaccagenin A.
2. The pharmaceutical composition for treating cor pulmonale according to claim 1, wherein: the weight parts of the dihydroquercetin and the procyanidin are 55-65, 35-45 and 15-20 respectively.
3. The pharmaceutical composition for treating cor pulmonale according to claim 1, wherein: the composition can be made into one or more of solution, tablet, capsule and pill.
4. The pharmaceutical composition for treating cor pulmonale according to claim 3, wherein: the composition also comprises auxiliary agents within a pharmaceutically allowable range, wherein the auxiliary agents are one or more of emulsifying agents, solubilizing agents, excipients or stabilizing agents.
5. The pharmaceutical composition for treating cor pulmonale according to claim 1, wherein: the preparation method of the phytolaccagenin A comprises the following steps: taking a proper amount of American pokeberry seeds, drying to constant weight, crushing, adding 70-95% ethanol, performing hot reflux extraction for at least 2 times, wherein the addition amount of the ethanol is 10-20 times of the dry weight of the medicinal materials, merging extracting solutions, concentrating to 1/10-1/5 of the dry weight of the medicinal materials, filtering, subjecting filtrate to nonpolar macroporous adsorption resin, performing static adsorption for at least 4 hours, washing with water for at least 10 column volumes, eluting with 10-20% ethanol for at least 6 column volumes, eluting with 40-50% ethanol for 3-5 column volumes, eluting with 70-80% ethanol for 5-7 column volumes, collecting 70-80% ethanol eluate, concentrating until no alcohol smell exists, filtering, collecting filtrate to obtain a column solution, and using a nonpolar organic solvent with a volume ratio of (2-1): 1: after the column solution is extracted for at least 2 times, the water layer is extracted with (3-1) a weak polar organic solvent with the volume ratio of 1: extracting the solution for 2-3 times, combining the weak-polarity organic solvents, concentrating, drying, crushing the dried substance, adding the composite solvent for recrystallization, collecting crystals, and drying to obtain phytolaccagenin A; the non-polar organic solvent comprises petroleum ether, and the weak-polar organic solvent comprises acetone, ethyl acetate or chloroform.
6. The pharmaceutical composition for treating cor pulmonale according to claim 5, wherein: the nonpolar macroporous adsorption resin comprises D101, HPD-100, ADS-8 or X-5.
7. The pharmaceutical composition for treating cor pulmonale according to claim 5, wherein: the recrystallization method of the dried substance comprises the following steps: dissolving the dried substance with acetic acid in an amount which is 2-3 parts by volume of the dried substance, centrifuging, preserving the heat of the supernatant at 40-50 ℃, dropwise adding methanol or ethanol under the condition of stirring, wherein the adding amount of the methanol or the ethanol is 8-10 times of that of the acetic acid, continuously dropwise adding triethylamine under the condition of preserving the heat and stirring after the methanol or the ethanol is added, wherein the adding amount of the triethylamine is 0.5-1.5 times of that of the acetic acid, cooling at room temperature, refrigerating in a 0 ℃ refrigerator overnight, taking out the product the next day, filtering, washing with water for crystallizing for at least 2 times, collecting crystals, and drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810641752.4A CN108904492B (en) | 2018-06-21 | 2018-06-21 | Pharmaceutical composition for treating pulmonary heart disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810641752.4A CN108904492B (en) | 2018-06-21 | 2018-06-21 | Pharmaceutical composition for treating pulmonary heart disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108904492A CN108904492A (en) | 2018-11-30 |
| CN108904492B true CN108904492B (en) | 2020-06-30 |
Family
ID=64419778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810641752.4A Active CN108904492B (en) | 2018-06-21 | 2018-06-21 | Pharmaceutical composition for treating pulmonary heart disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108904492B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102659751A (en) * | 2012-04-24 | 2012-09-12 | 南京泽朗医药科技有限公司 | Method for extracting purified americanol A |
-
2018
- 2018-06-21 CN CN201810641752.4A patent/CN108904492B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102659751A (en) * | 2012-04-24 | 2012-09-12 | 南京泽朗医药科技有限公司 | Method for extracting purified americanol A |
Non-Patent Citations (2)
| Title |
|---|
| Antioxidative catechol lignans/neolignans isolated from defatted kernel of Jatropha curcas;Toshisada Suzuki等;《J Wood Sci》;20160525;第62卷(第4期);3185-3186 * |
| Convenient Syntheses of Neurotrophic Americanol A and lsoamericanol A by HRP Catalyzed Oxidative Coupling of Caffeic Acid;Keiji Matsumoto等;《Tetrahedron Letters》;19991231;第40卷(第16期);339-348 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108904492A (en) | 2018-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100998552A (en) | Composition of oral medicine preparation and its preparing method | |
| CN109010414B (en) | Use of extract of Pithecellobium clypearia for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia | |
| DK172879B1 (en) | Silibinin-containing pharmaceutical composition | |
| WO2018133563A1 (en) | Panax plant extract and pharmaceutical composition and use thereof | |
| KR20110061976A (en) | Pharmaceutical composition for preventing or treating myocardial infarction containing the membrane-separated extracts of platycodon grandiflorum as an active ingredient | |
| CN108904492B (en) | Pharmaceutical composition for treating pulmonary heart disease | |
| CN106421075B (en) | A kind of preparation method and application of bamboo willow antioxidant activity component | |
| JP2002528511A (en) | Stabilized anticancer composition based on crude drug and method for producing the same | |
| CN115444893B (en) | Uric acid reducing active substance composition and application thereof | |
| TWI678211B (en) | Uses of cistanche tubulosa extract and isoacteoside in protecting muscles | |
| CN113116868B (en) | Use of tetrahydrocannabinol for the prevention and/or treatment of pulmonary hypertension | |
| CN101199560A (en) | Ginkgo leaf extract and preparing method thereof | |
| CN110151774B (en) | Application of flavonoid compound in coreopsis tinctoria and pharmaceutical composition thereof in preparation of medicine for treating acute pancreatitis | |
| EP2899186B1 (en) | New hydroxysafflor yellow pharmaceutical salts | |
| CN1314402C (en) | Drug composition containing fructus tribuli fruit total saponin and its preparation method | |
| CN113827587A (en) | Application of salvianolic acid A in preparing medicine for preventing thrombotic cerebral ischemia | |
| CN110101802A (en) | A kind of pharmaceutical composition for treating hypertension | |
| CN109771596A (en) | A kind of Antibicrobial anti inflammatory capsule and preparation method thereof | |
| CN107029002A (en) | The preparation method and new application of Chinese lobelia extract | |
| EP3787657B1 (en) | Herbal medicines for treating polycystic kidney diseases | |
| CN103830221A (en) | Applications of hydroxysafflor yellow A in preparation of medicines used for treating cardiovascular diseases | |
| CN103622985B (en) | The effect of amarogentin treatment pulmonary hypertension and application thereof | |
| CN109288835B (en) | Application of compound in preparation of medicine for treating acute pulmonary embolism | |
| CN106581027B (en) | Compound and pharmaceutical application, composition and preparation thereof | |
| CN103127106B (en) | Purpose of phencynonate hydrochloride for treating or relieving myocardial damage induced by myocardial ischemia reperfusion and pharmaceutical compositions including phencynonate hydrochloride |
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 |