Composition for heart disease, its active ingredients, method to prepare same and uses thereof

Abstract

This invention provides a composition for heart disease comprising extracts from raw herbs of 80.0-97.0% Radix Salviae Miltorrhizae, 1.0-19.0% Panax Notoginseng and 0.1-1.0% Borneol and its active ingredients. This invention also provides a method for preparing said composition and the active ingredients of the composition. Finally, this invention provides various uses of said compositions and the active ingredients.

1 . A composition for treatment of heart disease comprising the extract of raw herbs of Radix Salviae Miltorrhizae, Panax Notoginseng and Borneol.  
     
     
         2 . A composition of  claim 1  comprising herb extracts from raw herbs of 80.0-97.0% Radix Salviae Miltorrhizae, 1.0-19.0% Panax Notoginseng and 0.1-1.0% Borneol.  
     
     
         3 . The composition of  claim 1  comprising extracts from raw herbs of 90.0-97.0% Radix Salviae Miltorrhizae, 2.5-9.6% Panax Notoginseng and 0.2-0.5% Borneol.  
     
     
         4 . The composition according to  claim 1  comprising extracts from raw herbs of 89.8% Radix Salviae Miltorrhizae, 9.6% Panax Notoginseng and 0.5% Borneol.  
     
     
         5 . The composition according to  claim 1 ,  2 ,  3 , or  4 , produced by the steps of: 
 a. obtaining an appropriate amount of smashed Radix Salviae Miltorrhizae and Panax Notoginseng;    b. Extracting the obtained Radix Salviae Miltorrhizae, and Panax Notoginseng in hot aqueous reflux at about 60-100° C.;    c. Filtering and combining the extracts to form a combined extract;    d. Concentrating the combined extract from step (c) into an appropriate ratio of the volume of the concentrated extract to the weight of the inputted herbal materials to form a concentrated extract;    e. Putting ethanol into the concentrated extract from step (d) to about 50-85% final concentration of ethanol, performing ethanol precipitation and forming a precipitated resolution;    f. Concentrating the supernatant liquid of the precipitated resulting from step (e) to form a plaster of about 1.15-1.45 in relative density; and    g. Mixing the plaster from step (f) with an appropriate amount of Borneol, thereby producing the composition of herb extract of Radix Salviae Miltorrhizae, Panax Notoginseng and Borneol.    
     
     
         6 . The composition according to  claim 1 ,  2 ,  3 , or  4 , comprising Sodium 3′4-dihydroxyphenyllactate, Protocatechuic Aldehyde, Salvianolic acid A, B, C, D, E, F, Rosemarinic acid, Ginsenoside Rg1, Ginsenoside Rb1, Ginsenoside Re, Notoginsenoside R1, and Borneol.  
     
     
         7 . A composition for treatment of chronic stable angina pectoris, comprising 5-40% water-soluble phenolic acid of Radix Salviae Miltorrhizae, 1-10% water-soluble saponin of Panax Notoginseng and 1-5% of Borneol.  
     
     
         8 . The composition according to  claim 7 , comprising 10-30% water-soluble phenolic acid of Radix Salviae Miltorrhizae, 2-6% water-soluble saponin of Panax Notoginseng and 1-3% of Borneol.  
     
     
         9 . A composition capable of treating chronic stable angina pectoris comprising about 0.14 to about 0.18 mg Danshensu per pill, at least 12.12 μg Sanchinoside R1 per pill and at least 56.26 μg Ginsenoside Rg1 per pill.  
     
     
         10 . The composition according to  claim 7 ,  8 , or  9 , produced by steps of: 
 a. Extracting Radix Salviae Miltorrhizae, Panax Notoginseng separately in hot aqueous reflux and filtering separately;    b. Concentrating filtrates separately;    c. Refining the concentrates separately using resin columns and concentrating, and getting refined water-soluble extract of Radix Salviae Miltorrhizae and refined water-soluble extract of Panax Notoginseng; and    d. Mixing the refined water-soluble extracts from step (c) with an appropriate amount of borneol, thereby producing a composition capable of treating chronic stable angina pectoris.    
     
     
         11 . The composition according to  claim 10 , produced by steps of: 
 (1) Extraction of water-soluble components of Panax Notoginseng    a. Diluting herbs with 5-7 parts of water;    b. Extracting water-soluble components of Panax Notoginseng by boiling in a tank with the air pressure between 0.04-0.06 mPa for 2 hours;    c. Repeating extraction under the same conditions for 1.5 hours;    d. Filtering of the extraction with 100-mesh net;    e. Refining the filtrate using macroporous adsorption resin eluting with ethanol; and    f. Concentrating the eluted extracts under decompressed conditions with the air input to 0.04-0.06 mPa and the vacuum to −0.076˜−0.088 mPa until the density is 1.33-1.35;    (2) Extraction of water-soluble components of Radix Salviae Miltorrhizae    a. Diluting herbs with 5-7 parts of water;    b. Extracting water-soluble components of Radix Salviae Miltorrhizae by boiling in a tank with the air pressure between 0.04-0.06 mPa for 2 hours;    c. Repeating extraction under the same conditions for 1.5 hours;    d. Filtering the extraction with 100-mesh net;    e. Concentrating the filtrates under decompressed conditions with the vacuum pressure −0.076˜−0.088 mPa until one Kg initial herb becomes one liter;    f. Precipitating the concentrates with ethanol;    g. Filtering the ethanol precipitates solution through 100-mesh net;    h. Concentrating the filtrates under decompressed conditions with input air pressure 0.04-0.06 mPa and the vacuum pressure 0.076˜31 0.088 mPa;    i. Refining the concentrates by polyamide chromatography, eluting with ethanol; and    j. Concentrating the refined extracts to the density of 1.33-1.35;    (3) Producing the pill    a. Mixing the extracts of Panax Notoginseng, the extracts of Radix Salviae Miltorrhizae, synthetic borneol and polyethylene glycol 6000 at the ratio of 4.0:20.6:1.9:79.5;    b. Melting the mixture;    c. Manufacturing the melted mixture to pills using the dropping machine with the following characteristics: the temperature of dropping pot is constantly 89-93° C., the cooling solution is liquid paraffin with a temperature lower than 8° C., the inner diameter of the dropping head is 1.8 mm, the outer diameter of the dropping head is 2.4 mm, the distance between the dropping head and the surface of cooling solution is 15 cm; and    d. Centrifugation of the pills at 800-1100 rpm for 15 minutes to remove oils.    
     
     
         12 . The composition for the treatment of chronic stable angina pectoris comprising Sodium 3′4-dihydroxyphenyllactate, Protocatechuic Aldehyde, Salvianolic acid A, B, C, D, E, F, Rosemarinic acid, Ginsenoside Rg1, Ginsenoside Rb1, Ginsenoside Re, Notoginsenoside R1, Borneol, etc.  
     
     
         13 . A composition for the treatment of heart disease comprising active ingredients extracted from Salvia miltiorrhiza Beg., Panax notoginseng or Ginseng, and Dryobalanops aromatica Geartu.F. or Cinnammon camphor., wherein the active ingredient extracted from Salvia miltiorrhiza Beg. consists of one or more ingredients selected from the group as follows: tanshinone, salvianolic acid, methyl tanshinonate, rosmarinic acid, methyl rosmarinate, danshexinkum, protocatechualdehyde, Sodium 3′4-dihydroxyphenyllactate, lithospermic acid; the active ingredient extracted from Panax notoginseng or Ginseng consisting of one or more ingredients selected from notoginsenoside and ginsenoside; the active ingredient extracted from Dryobalanops aromatica Geartu.F. or Cinnammon camphor selected from d-borneol or l-borneol or both of them.  
     
     
         14 . The composition according to  claim 13 , wherein the said tanshinone is one or more ingredients selected from the group as follows: tanshinone I, tanshinone IIA, tanshinone IIB, tanshinone V, tanshinone VI, isotanshinone, miltirone, dihydrotanshinone, 1-dehydrotanshinone, and neocryptotanshinone.  
     
     
         15 . The composition according to  claim 13 , wherein the said salvianolic acid is one or more ingredients selected from the group as follows: Salvianolic acid A, Salvianolic acid B, Salvianolic acid C, Salvianolic acid D, Salvianolic acid E, Salvianolic acid G, and Salvianolic acid I.  
     
     
         16 . The composition according to  claim 13 , wherein the said lithospermic acid is one or more ingredients selected from the group as follows: lithospermic acid B, ethyl lithospermate, dimethyl lithospermate, and monomethyl lithospermate.  
     
     
         17 . The composition according to  claim 13 , wherein the ginsenoside is one or more ingredients selected from the group as follows: ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Rg3, ginsenoside Rh1, and ginsenoside Rh2.  
     
     
         18 . The composition according to  claim 13 , wherein the said notoginsenoside is one or more ingredients selected from the group as follows: notoginsenoside R1, notoginsenoside R2, notoginsenoside-R3, notoginsenoside R4, notoginsenoside R6, and notoginsenoside R7.  
     
     
         19 . The composition according to  claim 13 , characterized by comprising Magnesium Salvianolate B or 3′4-dihydroxyphenyllactate extracted from the Salvia miltiorrhiza Beg., Ginsenoside Rb 1  extracted from the Panax notoginseng or Ginseng, and d-Borneol extracted from the Dryobalanops aromatica Geartu.F. or Cinnammon camphor.  
     
     
         20 . The composition according to  claim 19 , characterized by comprising 10-80 mg of Magnesium Salvianolate B, 10-50 mg of Ginsenoside Rb 1  and 5-30 mg of d-Borneol.  
     
     
         21 . The composition according to  claim 20 , characterized by comprising 50 mg of Magnesium Salvianolate B, 20 mg of Ginsenoside Rb 1  and 15 mg of d-Borneol.  
     
     
         22 . The composition according to  claim 19 , characterized by comprising 5-80 mg of sodium 3′4-dihydroxyphenyllactate, 10-50 mg of Ginsenoside Rb 1  and 5-30 mg of d-Borneol.  
     
     
         23 . The composition according to  claim 22 , characterized by comprising 20 mg of sodium 3′4-dihydroxyphenyllactate, 20 mg of Ginsenoside Rb 1  and 15 mg of d-Borneol.  
     
     
         24 . The composition comprising one or more excipients such as polyethylene glycol, xylitol, lactobacillus, starch for preparation of dripping pills, wherein 50 mg of Magnesium Salvianolate B, 20 mg of Ginsenoside Rb 1 , 15 mg of d-Borneol and 265 mg of excipient are contained per ten dripping pill.  
     
     
         25 . The composition according to one of claims  13 - 24 , wherein the Salvianolate B was extracted by steps of: 
 a. Pulverizing Salvia miltiorrhiza Beg. into a fine powder, and decocting twice with hot water;    b. Combining the decoctions, and concentrating vacuum conditions under 50° C.;    c. Loading the solution from step (b) into macroporous adsorption resin and, after washing with water, eluting column with 40% ethanol;    d. After recovering the ethanol from the solution obtained in step (c), refining it by Sephadex LH-20 or other gel columns with similar characteristics, eluting with ethanol and collecting eluant containing Magnesium Salvianolate B; and    e. Repeating the process of step (d) until the concentration of Magnesium Salvianolate B reaches more than 90%.    
     
     
         26 . The composition according to one of claim  13 - 24 , wherein the Ginsenoside Rb 1  was extracted by steps of: 
 a. Pulverizing Panax notoginseng or Ginseng into a fine powder, and decocting with water; or refluxing with 70% ethanol; or percolating with 70% ethanol;    b. Recovering solvent from the solution at reduced pressure;    c. Loading the solution from step (b) into macroporous adsorption resin and, after washing with water, eluting column with 40% ethanol;    d. After recovering the ethanol from the solution obtained in step (c), refining it by silica gel column;    e. Eluting the column with chloroform, methanol and water in the ratio of 6:3:1, respectively, and collecting eluant; and    f. Using TLC for examination of Ginsenoside Rb 1  and recovering the solvent, thereby obtaining Ginsenoside Rb 1 .    
     
     
         27 . The composition according to one of claims  13 - 24 , wherein d-Borneol was extracted from trunk of Dryobalanops aromatica Geartu.F. or leaves of Cinnammon camphor. by means of vapor distillation, or supercritical carbon dioxide extraction.  
     
     
         28 . The compositions according to one of claims  1 - 27 , formulated in a dropping pellet, pill, capsule, granule, tablet, suspension, injection, syrup, tincture, powder, tea, topical solution, nebula, suppository microcapsule, or other pharmaceutically acceptable form.  
     
     
         29 . The compositions according to one of claims  1 - 28 , capable of increasing blood volume in coronary artery, relaxing the smooth muscles of blood vessels, improving the peripheral circulation, raising the oxygen content in veins, or significantly improving the acute myocardial ischemia or myocardial infarction, protecting the cells from damage by hypoxia or anoxia, protecting cells suffering from myocardial ischemia, improving micro-circulation, preventing arrhythmia, preventing platelets aggregation, thrombosis and dissolve fibrin, lowering blood viscosity, adjusting the blood cholesterol or preventing atherosclerosis, raising the tolerance to hypoxia or anoxia, preventing the oxidation of lipoprotein or removing the harmful free radicals, lowering plasma ET content, significantly improve the liver, kidneys and pancreas functions, preventing the occurrence or development of blood vessel or nerve diseases, enhancing the immune system, regulating the vascular nervous balance.  
     
     
         30 . The compositions according to one of claims  1 - 28 , capable of preventing and treating cardiovascular and cerebrovascular diseases, kidney disease, liver disease, pneumonia, lung or heart disease, pancreatitis, diabetes, vertebral disease, optic vessels disease, optic nerves disease, eccentric headache, chronic stomachitis, dizziness, bone diseases, altitude diseases, common elderly diseases; treating stable angina pectoris, unstable angina pectoris, aged angina pectoris, non-symptomatic myocardial ischemia, different types of coronary heart diseases or angina pectoris diseases, treating arrhythmia, enlargement of left ventricle, myocarditis, myocardial infarction or cerebral infraction, treating hyperlipidaemia, high blood viscosity syndrome or high blood pressure, treating diseases caused by micro-circulation disorder, treating stroke, cerebral infarction, cerebral bleeding and other cerebral diseases, treating hepatitis B, chronic liver fibrosis, liver fibrosis, active liver cirrosis, liver cirrosis in compensation period and other related diseases, treating kidney syndrome and its conjunctive diseases, treating diabetes or its conjunctive diseases, treating cyanosis-typed optic vessels diseases such as venal blockage in retina, central optic artery blockage in retina, high blood pressure optic atherosclerosis in retina, diabetic retinopathy, cento-neuropathy, cento-osmotic neuropathy, ischemic neuropathy, optic neuritis or optic nervous dystrophy, treating dizziness caused by cerebral-arterial ischemia, Meniere's disease, high blood pressure, coronary heart disease, treating detrimental death of epicondylus medialis, femoral end necrosis, twisted joint, ligament damage, fracture and proliferation of bone cells, treating bronchitis in children, treating hypoxia or anoxia, treating Alzheimer's Disease.  
     
     
         31 . A dropping machine for manufacturing a small-sized medicament comprising any one of compositions of claims  1 - 28 , which can be readily dissolved thus readily delivered to organs, comprising the parts of: 
 a. Dropping pot in which the temperature of liquid is 60-100° C.;    b. Apparatus which holds liquid paraffin cooling solution of which temperature is lower than 8° C.; and    c. Dropping head with 1.8 mm inner diameter and 2.35 mm outer diameter which distanced from the surface of cooling solution by approximately 15 cm, said dropping head allowing the dropping speed of over 30 pellets per minute.    
     
     
         32 . A method of determining the active fractions of any one of compositions of claims  1 - 28  which are capable of treating and preventing cardiovascular disease, wherein said method comprising the steps of: 
 a. Fractionating pharmaceutical compositions by high performance liquid chromatography (HPLC);    b. Comparing the retention time of the fractions of pharmaceutical compositions with the retention time of saponin R1, saponin Rg1, and saponin Re; and    c. Determining if pharmaceutical compositions contain fractions of which retention time is equivalent to the retention time of saponin R1, saponin Rg1, and saponin Re.    
     
     
         33 . A method of determining the active fractions of any one of compositions of claims  1 - 28  which are capable of treating and preventing cardiovascular disease, wherein said comprising the steps of: 
 a. Fractionating a pharmaceutical composition by thin layer chromatography (TLC);    b. Comparing the position and color of the fractions of pharmaceutical compositions with the position and color of 3,4-dihydroxyphenyl lactic acid and Protocatechuic Aldehyde; and    c. Determining if pharmaceutical compositions contain the fractions of which position and color are equivalent to the position and the color of 3,4-dihydroxyphenyl lactic acid and Protocatechuic Aldehyde.