Purification method of coenzyme Q10 and coenzyme Q10 composition

Abstract

According to the purification method, the yield is increased through a microwave method, and the coenzyme Q10 is matched with 20-30 parts of radix ophiopogonis, 15-25 parts of angelica sinensis, 20-30 parts of codonopsis pilosula, 18-22 parts of astragalus membranaceus, 20-30 parts of ginseng, 5-15 parts of cordyceps sinensis, 20-30 parts of ginger processed pinellia, 18-22 parts of pericarpium citri reticulatae, 15-25 parts of semen lepidii, 20-30 parts of semen brassicae, 30-40 parts of poria cocos, 20-30 parts of rhizoma atractylodis macrocephalae, 15-25 parts of peach kernels, 10-20 parts of safflower carthamus, 15-25 parts of ligusticum wallichii and the like. By tonifying heart qi and lung qi, warming lung and reducing phlegm, removing stasis and diminishing swelling, purging lung and promoting diuresis, tonifying spleen and excreting dampness, eliminating phlegm and resolving fluid retention, and promoting blood circulation and removing blood stasis, the traditional Chinese medicine composition has a good effect on treating the phlegm and fluid retention lung syndrome type heart failure.

Description

Technical Field

[0001] The patent of this invention relates to the technical field of chemical products, and in particular to a method for purifying coenzyme Q10 and a coenzyme Q10 composition. Background Art

[0002] Coenzyme Q10 is a coenzyme present in all eukaryotic organisms that perform aerobic respiration. Its structure is similar to vitamin K. Its main function is to drive human cells to produce energy. Coenzyme Q10 is mainly involved in the mitochondrial oxidative phosphorylation and ATP production process, regulates the cell redox environment, carries reduced electrons into the vesicle or out of the cell during the electron membrane penetration process, and participates in the formation of the proton gradient of the inner membrane and plasma membrane. It can accelerate cell renewal and stimulate cell activity, thereby greatly promoting the ability of cells to absorb nutrients. Adding coenzyme Q10 ingredients to skin care products can effectively help skin cells actively absorb other nutrients in skin care products, and has health-preserving effects such as accelerating metabolism and slowing down aging. As a health product, coenzyme Q10 has the functions of protecting the heart, enhancing energy, and improving immunity. It is suitable for athletes, high-intensity mental workers, and the stabilization and recovery of patients with heart disease, diabetes, etc.

[0003] The existing separation and purification process of coenzyme Q10 uses column separation method. This is because 5-demethoxy coenzyme Q10 in coenzyme Q10 is difficult to separate by other conventional methods, and can only be separated by column chromatography. However, column chromatography has disadvantages such as low production efficiency and high silica gel regeneration cost, which limits the industrial development of coenzyme Q10. Therefore, in order to realize the industrialization of coenzyme Q10 preparation by fermentation, it is necessary to explore and solve the problem from the aspects of extraction, separation, purification and other refining processes of crude products. Summary of the invention

[0004] The purpose of this application is to overcome at least one of the deficiencies of the prior art, and to provide a method for purifying coenzyme Q10 and a coenzyme Q10 composition, as well as a coenzyme Q10 composition that can effectively improve heart failure of phlegm-retention obstruction lung syndrome. To this end, the embodiments of this application disclose at least the following technical solutions:

[0005] A method for purifying coenzyme Q10 comprises the following steps:

[0006] (1) Add crude coenzyme Q10 and anhydrous ethanol to a reaction kettle, add NaCl solution dropwise to the reaction kettle under low temperature stirring, mix well, adjust pH with NaOH solution, stir at room temperature, place in a constant temperature water bath, centrifuge, take the supernatant and adjust pH with HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash with distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method;

[0007] (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction for 3 times. After vacuum drying, coenzyme Q10 with a purity greater than 99% is obtained.

[0008] The method for purifying coenzyme Q10 comprises the following steps:

[0009] (1) Add crude coenzyme Q10 and anhydrous ethanol to a reaction kettle, add 0.1 mol / L NaCl solution dropwise to the reaction kettle under low temperature stirring, and mix well. Then adjust the pH to 9-11 with 2 mol / L NaOH solution, stir at room temperature, keep in a constant temperature water bath at 54°C for 35 minutes, centrifuge at 4000 r / min for 20 minutes, take the supernatant and adjust the pH to 4-5.5 with 2 mol / L HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash it three times with 3 volumes of distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method;

[0010] (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction, with a solid-liquid ratio of 1:5-1:10, a microwave power of 200 W, a microwave extraction time of 3 h, and an extraction number of 3 times. After negative pressure drying, coenzyme Q10 with a purity greater than 99% is obtained.

[0011] The method for purifying coenzyme Q10 comprises the following steps:

[0012] (1) Add crude coenzyme Q10 and anhydrous ethanol to a reactor, add 0.1 mol / L NaCl solution dropwise to the reactor under low temperature stirring, and mix well. Then adjust the pH to 10 with 2 mol / L NaOH solution, stir at room temperature for 30 min, keep in a constant temperature water bath at 54°C for 35 min, centrifuge at 4000 r / min for 20 min, take the supernatant and adjust the pH to 4.9 with 2 mol / L HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash it three times with 3 volumes of distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method.

[0013] (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction, with a solid-liquid ratio of 1:5-1:10, a microwave power of 200 W, a microwave extraction time of 3 h, and an extraction number of 3 times. After negative pressure drying, coenzyme Q10 with a purity greater than 99% is obtained.

[0014] A coenzyme Q10 composition is extracted from the following raw materials in parts by weight: 20-30 parts of ophiopogon japonicus, 15-25 parts of angelica sinensis, 20-30 parts of codonopsis pilosula, 18-22 parts of astragalus, 20-30 parts of ginseng, 5-15 parts of cordyceps sinensis, 20-30 parts of pinellia ternata, 18-22 parts of tangerine peel, 15-25 parts of scutellaria baicalensis seeds, 20-30 parts of white mustard seeds, 30-40 parts of tuckahoe, 20-30 parts of atractylodes macrocephala, 15-25 parts of peach kernel, 10-20 parts of safflower, 15-25 parts of ligusticum chuanxiong, and 0.03-0.06 parts of coenzyme Q10 prepared by the above method.

[0015] The coenzyme Q10 composition is extracted from the following raw materials in parts by weight: 25 parts of ophiopogon japonicus, 20 parts of angelica sinensis, 25 parts of codonopsis pilosula, 20 parts of astragalus, 25 parts of ginseng, 10 parts of cordyceps sinensis, 25 parts of pinellia ternata, 20 parts of tangerine peel, 20 parts of scutellaria baicalensis seeds, 25 parts of white mustard seeds, 35 parts of tuckahoe, 25 parts of atractylodes macrocephala, 20 parts of peach kernel, 15 parts of safflower, 20 parts of ligusticum chuanxiong, and 0.04 parts of coenzyme Q10 prepared by the above method.

[0016] The coenzyme Q10 composition has a preparation method comprising: taking the above-mentioned Chinese medicinal raw materials of ophiopogon japonicus, angelica sinensis, codonopsis pilosula, astragalus membranaceus, ginseng, cordyceps sinensis, pinellia ternata, tangerine peel, scutellaria baicalensis, mustard seed, tuckahoe, atractylodes macrocephala, peach kernel, safflower, and ligusticum chuanxiong, soaking them in 5-12 times the amount of water for 1-2 hours, performing a first reflux extraction for 1-2 hours, filtering, and setting aside the filtrate, adding 5-10 times the amount of water to the residue, performing a second reflux extraction for 1-2 hours, filtering, combining the two filtrates, concentrating, drying, adding coenzyme Q10, and preparing a solid preparation.

[0017] The coenzyme Q10 composition, the solid preparation is one of tablets, capsules and granules.

[0018] The use of the coenzyme Q10 composition in the preparation of a drug for treating heart failure of phlegm-retention obstruction of the lung syndrome.

[0019] Experimental studies have shown that microwave extraction can improve the purity of coenzyme Q10.

[0020] Heart failure is a common disease in cardiovascular medicine. Most patients develop the disease due to infection, arrhythmia and other reasons, which affect the patient's heart function. According to the textbook of integrated Chinese and Western medicine internal medicine, it is divided into four types, namely qi deficiency and blood stasis, qi and yin deficiency, yang deficiency and water overflow, and phlegm and fluid blocking the lungs. The details are as follows: 1. Qi deficiency and blood stasis: It is the basic symptom of heart failure and can be seen in all stages of heart failure. It is mainly due to the invasion of external evils, dietary preferences, emotional injuries, congenital deficiencies, old age and physical weakness, etc., which affect the heart and lead to weak heart qi. According to TCM, the heart governs the blood vessels, and qi is the commander of blood. When qi moves, blood moves. When the heart qi is insufficient and the blood is weak, it will cause poor blood flow, resulting in depression, fatigue, palpitations, hypoxia and other symptoms; 2. Qi and yin deficiency: Qi deficiency leads to qi transformation dysfunction, resulting in reduced yin fluid production; 3. Yang deficiency and water overflow: According to TCM, the kidney governs water, which is the main regulator of the distribution and excretion of water in the body. When kidney yang is deficient, qi cannot transform fluid, and water distribution is unbalanced. When it overflows on the skin, edema symptoms will occur; 4. Phlegm and fluid blocking the lungs: According to TCM, all diseases are caused by phlegm. When the heart and lung qi are deficient, water and moisture cannot be transformed, and the lungs are blocked. When the lungs lose their clearing and purification, phlegm and fluid blocking the lungs will occur. Clinical manifestations include: coughing, wheezing, shortness of breath, opening the mouth and raising the shoulders, unable to lie flat, sputum is white or thick yellow, palpitations and irritability, chest tightness and abdominal distension, blue face and sweating, and cyanosis of the lips. The tongue is dark purple, the tongue coating is thick and greasy or white or yellow, and the pulse is stringy, slippery and rapid.

[0021] Among them, phlegm and fluid blocking the lung type of heart failure is the most common. Pathogenesis analysis: phlegm and fluid blocking the lung type of heart failure is a syndrome of deficiency in the root and excess in the superficial symptoms. When the heart and lung qi are deficient, the spleen and kidney are both diseased, water and moisture cannot be transformed, and gather to form phlegm, which blocks the lungs. The lungs lose their ability to clear and purify, resulting in coughing, wheezing, shortness of breath, opening the mouth and raising the shoulders, inability to lie flat, and excessive phlegm; if the phlegm does not turn into heat, the phlegm is white, and the tongue coating is thick and greasy; if the phlegm is stagnant and turns into heat, the phlegm is yellow and thick, coughing and vomiting are uncomfortable, and the tongue coating is thick and greasy; if the phlegm is turbid and disturbs the mind, the heart is uneasy, and the heart is palpitated and irritable; if the phlegm blocks blood stasis and the qi is stagnant, the chest is stuffy, the face is blue and the lips are purple, and the tongue is dark purple; sweat is the fluid of the heart, and spontaneous sweating occurs when the heart qi is insufficient. A stringy and slippery pulse is a sign of phlegm and fluid, and a rapid pulse can be a sign of phlegm heat or a sign of weak heart qi.

[0022] The present invention uses tonifying heart qi and tonifying lung qi, and tonifying both heart and lung as main treatment principles, wherein Ophiopogon japonicus, Chinese angelica and Codonopsis pilosula tonify heart qi, and have the effects of enhancing myocardial function, improving cardiac metabolism and energy supply; Astragalus membranaceus, ginseng and Cordyceps sinensis tonify lung qi, and can nourish yin and qi, moisten the lungs and relieve cough; Ophiopogon japonicus, Chinese angelica, Codonopsis pilosula, Astragalus membranaceus, ginseng and Cordyceps sinensis are all monarch drugs; Pinellia ternata and dried orange peel warm the lungs and resolve phlegm, disperse nodules and reduce swelling, and promote qi; Lepidium membranaceus and Sinapis alba drain the lungs and expel water; wherein Lepidium membranaceus drains the lungs and promotes water expulsion, Sinapis alba drains the lungs and promotes water expulsion; The phlegm outside the membrane of the seed is removed, and ginger, pinellia, tangerine peel, scutellaria, and white mustard seeds are all used as assistant drugs; due to deficiency of heart and lung qi, spleen and kidney are both diseased, and phlegm blocks blood stasis, and qi is stagnant, Poria and Atractylodes are used to invigorate the spleen and eliminate dampness, eliminate phlegm and resolve fluid. The spleen produces the lungs, which is like earth producing gold, such as spleen qi transportation and transformation, transforming qi to fill the lungs. Peach kernel, safflower, and Chuanxiong promote blood circulation and resolve blood stasis. Peach kernel is heavy and sinks, tends to enter the interior, is good at moving to the lower burner, and is good at breaking up blood stasis in the internal organs; safflower is light and rises, moves to the outside and reaches the upper part, dredges the meridians and collaterals, and is good at removing blood stasis in the meridians and above. The two medicines are used together to enhance the effects of promoting blood circulation, unblocking menstruation, removing blood stasis and promoting new blood, reducing swelling and relieving pain. Peach kernel tastes bitter and sweet, and is neutral in nature; it enters the heart and liver meridians, while safflower tastes pungent and is warm in nature. It enters the heart and liver meridians, both belong to the liver meridian, and the liver produces the heart, which is like wood producing fire. For example, the liver stores blood to help the heart, and the liver's regulation of blood helps the heart circulate blood, so they are all adjuvant drugs. The whole formula contains Ophiopogon japonicus, Angelica sinensis, Codonopsis pilosula, Astragalus membranaceus, Ginseng, Cordyceps sinensis, Pinellia ternata, Tangerine peel, Lemongrass seed, White mustard seed, Poria cocos, Atractylodes macrocephala, peach kernel, safflower, and Chuanxiong, and coenzyme Q10 is added, which can replenish heart and lung qi, warm the lungs and resolve phlegm, disperse stagnation and reduce swelling, drain the lungs and promote diuresis, strengthen the spleen and eliminate dampness, remove phlegm and resolve fluid, promote blood circulation and remove blood stasis, and has a good effect in treating heart failure with phlegm and fluid blocking the lungs. DETAILED DESCRIPTION

[0023] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, but these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0024] Embodiment 1:

[0025] (1) 1000 ml of coenzyme Q10 fermentation broth was filtered through a ceramic membrane to obtain a crude product;

[0026] (2) 200 g of crude coenzyme Q10 and 10 times the weight of anhydrous ethanol were added to a reaction kettle. Under low temperature stirring, 0.1 mol / L NaCl solution was added dropwise to the reaction kettle to mix well. Then, the pH was adjusted to 10 with 2 mol / L NaOH solution. The mixture was stirred at room temperature for 30 min. After being kept in a constant temperature water bath at 54°C for 35 min, the mixture was centrifuged at 4000 r / min for 20 min. The supernatant was taken and the pH was adjusted to 4.9 with 2 mol / L HCl. The mixture was allowed to stand at 4°C overnight. After centrifugation under the same conditions, the precipitate was taken and then washed three times with 3 times the volume of distilled water. The precipitate was freeze-dried to obtain coenzyme Q10 extracted by the alkali dissolution and acid precipitation method.

[0027] (3) The coenzyme Q10 prepared in step (1) was added with anhydrous ethanol and subjected to microwave extraction with a solid-liquid ratio of 1:8, a microwave power of 200 W, a microwave extraction time of 3 h, and a number of extractions of 3 times. After vacuum drying, 142 g of coenzyme Q10 with a purity greater than 99% was obtained.

[0028] Comparative Example 1:

[0029] (1) 1000 ml of coenzyme Q10 fermentation broth was filtered through a ceramic membrane to obtain a crude product;

[0030] (2) 200 g of crude coenzyme Q10 and 10 times the weight of anhydrous ethanol were added to a reaction kettle. Under low temperature stirring, 0.1 mol / L NaCl solution was added dropwise to the reaction kettle to mix well. Then, the pH was adjusted to 10 with 2 mol / L NaOH solution. The mixture was stirred at room temperature for 30 min. After being kept in a constant temperature water bath at 54°C for 35 min, the mixture was centrifuged at 4000 r / min for 20 min. The supernatant was taken and the pH was adjusted to 4.9 with 2 mol / L HCl. The mixture was allowed to stand at 4°C overnight. After centrifugation under the same conditions, the precipitate was taken and then washed three times with 3 times the volume of distilled water. The precipitate was lyophilized to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method. A total of 159 g of coenzyme Q10 was obtained, and the purity of the content was 85%.

[0031] The above results show that microwave extraction can improve the purity of coenzyme Q10.

[0032] Embodiment 2:

[0033] Take 25g of Ophiopogon japonicus, 20g of Angelica sinensis, 25g of Codonopsis pilosula, 20g of Astragalus membranaceus, 25g of Ginseng, 10g of Cordyceps sinensis, 25g of Pinellia ternata, 20g of Tangerine peel, 20g of Lemongrass seeds, 25g of White Sinapis seeds, 35g of Poria cocos, 25g of Atractylodes macrocephala, 20g of Peach kernel, 15g of Carthamus tinctorius, 20g of Ligusticum chuanxiong, and 0.04g of Coenzyme Q10 prepared in Example 1. The above-mentioned Chinese medicinal raw materials Ophiopogon japonicus, Angelica sinensis, Codonopsis pilosula, Astragalus membranaceus, Ginseng, Cordyceps sinensis, Pinellia ternata, Tangerine peel, Lemongrass seeds, White Sinapis seeds, Poria cocos, Atractylodes macrocephala, Peach kernel, Carthamus tinctorius, and Ligusticum chuanxiong are soaked in 8 times the amount of water for 2h, refluxed for 1h for the first time, filtered, and the filtrate is reserved. Add 10 times the amount of water to the residue, refluxed for 1h for the second time, filtered, and the two filtrates are combined, concentrated, dried, and coenzyme Q10 is added to prepare granules.

[0034] Embodiment 3:

[0035] Take 20g of Ophiopogon japonicus, 25g of Angelica sinensis, 20g of Codonopsis pilosula, 22g of Astragalus membranaceus, 20g of Ginseng, 15g of Cordyceps sinensis, 20g of Pinellia ternata, 22g of Tangerine peel, 15g of Lepidium tiliaceum, 30g of White Sinapis, 30g of Poria cocos, 30g of Atractylodes macrocephala, 15g of Peach kernel, 20g of Safflower, 15g of Chuanxiong, and 0.06g of Coenzyme Q10. , Cordyceps sinensis, Pinellia ternata, Tangerine peel, Lepidium tiliaceus, White mustard seed, Poria cocos, Atractylodes macrocephala, Peach kernel, Safflower, and Ligusticum chuanxiong, soak in 5-12 times the amount of water for 1-2 hours, reflux extraction for the first time for 1-2 hours, filter, and reserve the filtrate, add 5-10 times the amount of water to the residue, reflux extraction for the second time for 1-2 hours, filter, combine the two filtrates, concentrate, dry, add coenzyme Q10, and prepare tablets.

[0036] Embodiment 4:

[0037] Take 30g of Ophiopogon japonicus, 15g of Angelica sinensis, 30g of Codonopsis pilosula, 18g of Astragalus membranaceus, 30g of Ginseng, 5g of Cordyceps sinensis, 30g of Pinellia ternata, 18g of Tangerine peel, 25g of Lepidium tiliaceum, 20g of Sinapis alba, 40g of Poria cocos, 20g of Atractylodes macrocephala, 25g of Peach kernel, 10g of Safflower, 25g of Chuanxiong, and 0.03g of Coenzyme Q100. The above Chinese medicinal raw materials Ophiopogon japonicus, Angelica sinensis, Codonopsis pilosula, Astragalus membranaceus, Ginseng, Cordyceps sinensis, pinellia tuber, tangerine peel, scutellaria baicalensis seed, white mustard seed, Poria cocos, Atractylodes macrocephala, peach kernel, safflower, and Chuanxiong are soaked in 5-12 times the amount of water for 1-2 hours, refluxed for the first time for 1-2 hours, filtered, and the filtrate is reserved. 5-10 times the amount of water is added to the residue, refluxed for the second time for 1-2 hours, filtered, and the two filtrates are combined, concentrated, dried, and coenzyme Q10 is added to prepare capsules.

[0038] Comparative Example 2:

[0039] Take 25g of Ophiopogon japonicus, 20g of Angelica sinensis, 25g of Codonopsis pilosula, 20g of Astragalus membranaceus, 25g of Ginseng, 10g of Cordyceps sinensis, 25g of Pinellia ternata, 20g of Tangerine peel, 20g of Lepidium tiliaceum, 25g of White mustard seed, 35g of Poria cocos, 25g of Atractylodes macrocephala, 20g of Peach kernel, 15g of Carthamus tinctorius, and 20g of Ligusticum chuanxiong. The above-mentioned Chinese medicinal raw materials Ophiopogon japonicus, Angelica sinensis, Codonopsis pilosula, Astragalus membranaceus, Ginseng, Cordyceps sinensis, Pinellia ternata, Tangerine peel, Lepidium tiliaceum, White mustard seed, Poria cocos, Atractylodes macrocephala, Peach kernel, Carthamus tinctorius, and Ligusticum chuanxiong are soaked in 8 times the amount of water for 2h, refluxed for 1h for the first time, filtered, and the filtrate is reserved for use. Add 10 times the amount of water to the residues, refluxed for 1h for the second time, filtered, and the two filtrates are combined, concentrated, and dried to prepare granules.

[0040] Example 5: Clinical study

[0041] 150 patients with heart failure of phlegm-retention obstruction lung syndrome were selected for study and randomly divided into three groups, namely, group 2 of the present invention, group 1 of comparative example, and group Q10 of coenzyme. The samples prepared in Example 2, comparative example 2, and Example 1 were taken respectively. The daily dosage of group 2 of the present invention was 25 g of Ophiopogon japonicus, 20 g of Angelica sinensis, 25 g of Codonopsis pilosula, 20 g of Astragalus membranaceus, 25 g of Ginseng, 10 g of Cordyceps sinensis, 25 g of Pinellia ternata, 20 g of Tangerine peel, 20 g of Lemongrass seeds, 25 g of Sinapis alba, 35 g of Poria, 25 g of Atractylodes macrocephala, 20 g of Peach kernel, 15 g of Carthamus tinctorius, 20 g of Ligusticum chuanxiong, and 20 g of Coenzyme Q10. 0.04g; the daily dosage of comparative example 2 is 25g of Ophiopogon japonicus, 20g of Angelica sinensis, 25g of Codonopsis pilosula, 20g of Astragalus membranaceus, 25g of Ginseng, 10g of Cordyceps sinensis, 25g of Pinellia ternata, 20g of Tangerine peel, 20g of Lepidium membranaceus, 25g of Sinapis alba, 35g of Poria, 25g of Atractylodes macrocephala, 20g of Peach kernel, 15g of Carthamus tinctorius, and 20g of Ligusticum chuanxiong; the daily dosage of the coenzyme Q10 group is 40mg, and it is taken continuously for 1 month.

[0042] Western medicine diagnostic criteria: Main clinical manifestations: typical symptoms and signs of heart failure; normal or slightly decreased LVEF (≥LVEF45%), and small left ventricle; evidence of related structural heart disease (such as left ventricular hypertrophy, left atrial enlargement) and (or) diastolic dysfunction; echocardiography shows no valvular heart disease, and can exclude pericardial disease, hypertrophic cardiomyopathy, restrictive (infiltrative) cardiomyopathy, etc. Other factors: in line with the epidemiological characteristics of this disease: most patients are elderly and female, the cause of heart failure is hypertension or a history of long-term hypertension, and some patients may have diabetes, obesity, atrial fibrillation, etc.; BNP and (or NT-proBNP) determination is of reference value. Diagnosis is made based on the above clinical manifestations and other factors.

[0043] TCM diagnostic criteria: Clinical manifestations of heart failure with phlegm-fluid obstruction of the lung syndrome include: coughing, wheezing, raising shoulders with open mouth, inability to lie flat, white or yellow thick sputum, palpitations, irritability, chest tightness, abdominal distension, blue face, sweating, cyanosis of lips, dark purple tongue, thick and greasy or white or yellow tongue coating, and stringy, slippery and rapid pulse.

[0044] Efficacy evaluation criteria: formulated in reference to the 2002 edition of "Guidelines for Clinical Research of New Chinese Medicines".

[0045] The improvement of cardiac function was classified according to the NYHA classification method. The efficacy criteria were as follows: (1) Significant effect: heart failure was basically controlled or cardiac function improved by more than 2 grades. (2) Effective: cardiac function improved by 1 grade but less than 2 grades. (3) Ineffective: cardiac function improved by less than 1 grade. (4) Deterioration: cardiac function deteriorated by 1 grade or more.

[0046] The efficacy of TCM syndromes, judgment criteria (1) marked effect: the main and secondary symptoms basically or completely disappeared, and the syndrome score after treatment was 0 or decreased by ≥70%. (2) effective: the syndrome score after treatment decreased by ≥30%. (3) ineffective: the syndrome score after treatment decreased by less than 30%. (4) worsening: the score after treatment exceeded the score before treatment.

[0047] The results are shown in Table 1 and Table 2:

[0048] Table 1 Improvement of cardiac function

[0049] Grouping Significant effect efficient invalid deterioration Total effective rate (%) Example 2 26 20 4 0 92 Comparative Example 2 21 19 9 1 80 Example 1 Coenzyme Q10 Group 18 16 14 2 68

[0050] Table 2 Therapeutic effect of TCM syndromes

[0051] Grouping Significant effect efficient invalid deterioration Total effective rate (%) Example 2 24 21 5 0 90 Comparative Example 2 16 25 7 2 82 Example 1 Coenzyme Q10 Group 18 19 12 1 74

[0052] As can be seen from Tables 1 and 2, after the Example 2 group of the present invention continuously took the sample prepared by the Example 2 group for one month, the effective rate of cardiac function improvement was 92%, of which 26 cases were markedly effective and 20 cases were effective; the effective rate of TCM syndrome efficacy was 90%, of which 24 cases were markedly effective and 21 cases were effective. Compared with the Comparative Example 2 group and the Coenzyme Q10 group of Example 1, it was significantly better than the Comparative Example 2 and the Coenzyme Q10 group of Example 1, indicating that the Chinese medicine compound and coenzyme Q10 have a synergistic effect in treating heart failure of phlegm and fluid obstruction of the lung syndrome.

[0053] Example 6: Pharmacodynamics Study

[0054] Establishment of doxorubicin-induced heart failure model: 100 SD rats were divided into a blank group, a model group, a group 2 of Example 2 of the present invention, a group 2 of Comparative Example, and a coenzyme Q10 group, with 20 rats in each group. The rats in the model group, the group 2 of Example 2 of the present invention, the group 2 of Comparative Example, and the coenzyme Q10 group of Example 1 were injected with doxorubicin (dosage 3х10 -3 g·kg -1 ), volume is 2mL·kg-1 , once every 5 days, that is, modeling was performed 3 times on D1, D6, and D11, with a cumulative dose of 9х10 -3 g·kg -1 The blank group was injected with an equal volume of normal saline via tail vein.

[0055] Heart failure function measurement: After successful modeling, each group slowly removed the cardiac catheter, performed tracheotomy, connected the ventilator at a frequency of 60 times / min, and the stimulated gas volume was 0.9 ml. Then, the thoracotomy was performed along the middle of the sternum to separate the ascending aorta, and an electromagnetic blood flowmeter probe with an inner diameter of 2 mm was placed. The MFV-1200 electromagnetic blood flowmeter was then used to measure and calculate the cardiac output (CO) and stroke volume (SV). The HR representing the heart rate (Heart Rate, HR) was calculated by electrocardiogram (ECG). The results are shown in Table 3.

[0056] Table 3 Heart pump function

[0057] Grouping CO(ml / min) SV (ml / beat) HR times / min Blank Group 186±6.9 0.536±0.016 376.7±32.8 Model Group 97±5.4## 0.254±0.011## 471.5±49.2## Example 2 179±7.2**&！ 0.521±0.015**&&！ 387.1±33.4**&&！ Comparative Example 2 124±6.8 0.365±0.013 452.9±42.6 Example 1 Coenzyme Q10 Group 112±8.7 0.379±0.018 449.0±38.1

[0058] Compared with the blank group, #P<0.05, ##P<0.01; compared with the model group, *P<0.05, **P<0.01; compared with the coenzyme Q10 group in Example 1, &P<0.05, &&P<0.01; compared with the comparative example 2 group, !P<0.05, !P<0.01.

[0059] As shown in Table 3, compared with the blank group, the model group had significant changes in cardiac output (CO), stroke volume (SV), and heart rate (HR), indicating that the heart failure model was successfully established; compared with the comparative example 2 group and the coenzyme Q10 group of Example 1, there were significant differences in the group 2 of Example 2 of the present invention, indicating that the present invention can improve the myocardial contractile function of rats with congestive heart failure, increase cardiac output and stroke volume, and reduce heart rate. At the same time, it is suggested that the Chinese medicine compound of the present invention and coenzyme Q10 heart failure rats have a synergistic effect in improving the cardiac pump function.

[0060] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for purifying coenzyme Q10, characterized in that: The steps include: (1) Add crude coenzyme Q10 and anhydrous ethanol to a reaction kettle, add NaCl solution dropwise to the reaction kettle under low temperature stirring, mix well, adjust pH with NaOH solution, stir at room temperature, place in a constant temperature water bath, centrifuge, take the supernatant and adjust pH with HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash with distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method; (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction for 3 times. After vacuum drying, coenzyme Q10 with a purity greater than 99% is obtained.

2. A method for purifying coenzyme Q10 as claimed in claim 1, characterized in that: The steps include: (1) Add crude coenzyme Q10 and anhydrous ethanol to a reaction kettle, add 0.1 mol / L NaCl solution dropwise to the reaction kettle under low temperature stirring, and mix well. Then adjust the pH to 9-11 with 2 mol / L NaOH solution, stir at room temperature, keep in a constant temperature water bath at 54°C for 35 minutes, centrifuge at 4000 r / min for 20 minutes, take the supernatant and adjust the pH to 4-5.5 with 2 mol / L HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash it three times with 3 volumes of distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method; (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction, with a solid-liquid ratio of 1:5-1:10, a microwave power of 200 W, a microwave extraction time of 3 h, and an extraction number of 3 times. After negative pressure drying, coenzyme Q10 with a purity greater than 99% is obtained.

3. A method for purifying coenzyme Q10 as claimed in claim 1, characterized in that: The steps include: (1) Add crude coenzyme Q10 and 10 times the weight of anhydrous ethanol into a reaction kettle, add 0.1 mol / L NaCl solution dropwise into the reaction kettle under low temperature stirring, and mix well. Then adjust the pH to 10 with 2 mol / L NaOH solution, stir at room temperature for 30 minutes, keep in a constant temperature water bath at 54°C for 35 minutes, centrifuge at 4000 r / min for 20 minutes, take the supernatant and adjust the pH to 4.9 with 2 mol / L HCl, and stand at 4°C overnight; take the precipitate after centrifugation under the same conditions, wash it three times with 3 times the volume of distilled water, and lyophilize to obtain coenzyme Q10 extracted by alkali dissolution and acid precipitation method; (2) The coenzyme Q10 prepared in step (1) is added with anhydrous ethanol and subjected to microwave extraction, with a solid-liquid ratio of 1:5-1:10, a microwave power of 200 W, a microwave extraction time of 3 h, and an extraction number of 3 times. After negative pressure drying, coenzyme Q10 with a purity greater than 99% is obtained.

4. A coenzyme Q10 composition, characterized in that: The invention is extracted from the following raw materials in parts by weight: 20-30 parts of ophiopogon japonicus, 15-25 parts of angelica sinensis, 20-30 parts of codonopsis pilosula, 18-22 parts of astragalus, 20-30 parts of ginseng, 5-15 parts of cordyceps sinensis, 20-30 parts of pinellia ternata, 18-22 parts of tangerine peel, 15-25 parts of scutellaria baicalensis seeds, 20-30 parts of white mustard seeds, 30-40 parts of tuckahoe, 20-30 parts of atractylodes macrocephala, 15-25 parts of peach kernel, 10-20 parts of safflower, 15-25 parts of ligusticum chuanxiong, and 0.03-0.06 parts of the coenzyme Q10 prepared according to claim 3.

5. A coenzyme Q10 composition according to claim 4, characterized in that: The invention is extracted from the following raw materials in parts by weight: 25 parts of ophiopogon japonicus, 20 parts of angelica sinensis, 25 parts of codonopsis pilosula, 20 parts of astragalus, 25 parts of ginseng, 10 parts of cordyceps sinensis, 25 parts of pinellia ternata, 20 parts of tangerine peel, 20 parts of scutellaria baicalensis seeds, 25 parts of white mustard seeds, 35 parts of tuckahoe, 25 parts of atractylodes macrocephala, 20 parts of peach kernel, 15 parts of safflower, 20 parts of ligusticum chuanxiong, and 0.04 parts of coenzyme Q10 prepared in Example 1.

6. A coenzyme Q10 composition according to claim 4, characterized in that: The preparation method is as follows: take the above-mentioned Chinese medicinal raw materials Ophiopogon japonicus, Angelica sinensis, Codonopsis pilosula, Astragalus membranaceus, Ginseng, Cordyceps sinensis, Pinellia ternata, Tangerine peel, Lepidium tiliaceus, Sinapis alba, Poria cocos, Atractylodes macrocephala, Prunus persica, Safflower, and Ligusticum chuanxiong, soak them in 5-12 times the amount of water for 1-2 hours, reflux extract for the first time for 1-2 hours, filter, and reserve the filtrate, add 5-10 times the amount of water to the residue, reflux extract for the second time for 1-2 hours, filter, combine the two filtrates, concentrate, dry, add coenzyme Q10, and prepare a solid preparation.

7. A coenzyme Q10 composition according to claim 5, characterized in that: The solid preparation is one of tablets, capsules and granules.

8. Use of a coenzyme Q10 composition as claimed in claim 4 in the preparation of a drug for treating heart failure of phlegm-retention obstruction of the lung syndrome.