Danhuang collateral dredging oral liquid with effects of dispersing blood stasis, dredging collaterals, tonifying qi and regulating middle energizer and method for improving biological performance of Danhuang

Abstract

The invention relates to a Danhuang collateral-dredging oral liquid with the effects of dispersing blood stasis, dredging collaterals, tonifying qi and regulating middle energizer and a method for improving the biological performance thereof. On one hand, the invention relates to a salvia miltiorrhiza and gynostemma pentaphyllum collateral dredging oral liquid which is prepared from salvia miltiorrhiza, gynostemma pentaphyllum total saponins, kiwi fruit juice and pharmaceutically acceptable auxiliary materials, and the weight ratio of the salvia miltiorrhiza to the gynostemma pentaphyllum total saponins to the kiwi fruit juice is 150g: 1g: 200g. The invention also relates to a method for preparing the Danhuang oral liquid capable of dredging collaterals, and application of the Danhuang oral liquid capable of dredging collaterals in preparation of medicines with the effects of dispersing blood stasis, dredging collaterals, tonifying qi and regulating middle energizer, or application of the Danhuang oral liquid in preparation of medicines for improving palpitation, chest distress, fatigue, shortness of breath, insomnia and inappetence caused by qi-blood deficiency. The salvia miltiorrhiza and blue collateral dredging oral liquid has excellent biological activity.

Description

Technical Field

[0001] The invention belongs to the field of medical technology and relates to a Chinese medicine oral liquid, in particular to a Danlan Tongluo oral liquid which has the effects of removing blood stasis and unblocking meridians, invigorating qi and regulating the middle, and can be used to improve symptoms such as palpitations, chest tightness, fatigue, shortness of breath, insomnia, loss of appetite and the like caused by deficiency of both qi and blood. The oral liquid is prepared from salvia miltiorrhiza, total saponins of gynostemma pentaphyllum and kiwi fruit juice. Background Art

[0002] Danlan Tongluo Oral Liquid is a traditional Chinese medicine preparation produced by the applicant Guizhou Liangji Pharmaceutical Co., Ltd. It has been used clinically for decades and has the functions of removing blood stasis and promoting blood circulation, invigorating qi and regulating the middle meridian. It can be used to improve symptoms such as palpitations, chest tightness, fatigue, shortness of breath, insomnia, and loss of appetite caused by qi and blood deficiency. The commercial specification is 10ml per bottle, for oral use, 1 bottle at a time, 3 times a day.

[0003] According to the national drug standard WS-5702 (B-0702)-2014Z of Danlan Tongluo oral liquid, its prescription per 1000ml is: 150g of Salvia miltiorrhiza, 1g of total saponins of Gynostemma pentaphyllum, and 200g of kiwi juice.

[0004] According to the above national drug standards, the method for preparing 1000ml of Danlan Tongluo oral liquid comprises the following steps: Take 150g of Danshen and add water to decoct three times, add 8 times the amount of water for 2 hours for the first time, add 6 times the amount of water for 1.5 hours for the second time, and add 4 times the amount of water for 1.5 hours for the third time, combine the decoctions, filter, and concentrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add hot water to dissolve, set aside, take another 120g of sucrose to make syrup, combine with the above concentrate and kiwi fruit juice, add water to 1000ml, mix well, filter, fill, sterilize, and obtain (sugar-containing Danlan Tongluo oral liquid); or Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, add hot water to dissolve, combine with the above-mentioned concentrate and kiwi juice, add water to 1000ml, mix well, filter, fill, and sterilize to obtain (sugar-free Danlan Tongluo oral liquid).

[0005] The total saponins of Gynostemma pentaphyllum used in Danlan Tongluo Oral Liquid are extracted from the whole herb of Gynosstemmapentaphyllum (Thunb.) Mak., a gourd root plant, and then refined. The kiwi fruit juice used in Danlan Tongluo Oral Liquid is obtained from the fresh fruit of Actinidia chinensis Planch., a plant of the genus Actinidia in the family Actinidia, after depilation, juicing, filtration and sterilization.

[0006] Cui Wei (Cui Wei, Study on the Quality of Danlan Tongluo Oral Liquid in Western Liaoning, China Health Industry, 2016, 13(29): 61) used high performance liquid chromatography to compare and analyze the content of protocatechuic aldehyde, the main ingredient, in five batches of Danlan Tongluo Oral Liquid from different manufacturers in three places in Western Liaoning (Jinzhou, Chaoyang, and Fuxin), and preliminarily explored the quality of Danlan Tongluo Oral Liquid in Western Liaoning. The results showed that the content of protocatechuic aldehyde in the randomly sampled Danlan Tongluo Oral Liquid in the region met the requirements of standard YBZ01722006.

[0007] CN1833676A (application number: 200610050909.3, Runfeng) discloses a Chinese medicine Danlan Tongluo oral preparation for treating ischemic diseases caused by deficiency of both qi and blood, which is made of 1250-1750 danshen, 10-15 total saponins of jiaogulan, and 1800-2300 kiwi fruit juice. These Chinese medicines are prepared and processed by conventional methods, wherein danshen is boiled, extracted and concentrated to obtain an extract with a relative density of 1.27-1.35 (40-50° C.), and conventional auxiliary materials are added to prepare oral solutions, tablets, granules, capsules, dripping pills and soft capsules. Compared with the existing drugs for treating diseases caused by deficiency of both qi and blood, it has a fast onset of action. After taking it, the patient can improve the symptoms of palpitation, chest tightness, fatigue, shortness of breath, insomnia, loss of appetite and the like caused by deficiency of both qi and blood in a relatively short period of time. The preparation is easy to carry and take, and has the characteristics of no toxic side effects when taken for a long time.

[0008] However, the prior art still requires a new method for preparing Danlan Tongluo oral liquid, for example, preparing Danlan Tongluo oral liquid with excellent properties such as biological properties. Summary of the invention

[0009] The object of the present invention is to provide a new method for preparing Danlan Tongluo oral liquid, for example, preparing Danlan Tongluo oral liquid with excellent properties such as biological properties. It has been unexpectedly found that the Danlan Tongluo oral liquid prepared by the present invention exhibits one or more beneficial effects as described in the context of the present invention. The present invention is completed based on such findings.

[0010] To this end, the first aspect of the present invention provides a Danlan Tongluo oral liquid, which is prepared from Danshen miltiorrhiza, Gynostemma pentaphyllum total saponins, kiwi fruit juice and pharmaceutically acceptable excipients.

[0011] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the weight ratio of Danshen, Gynostemma pentaphyllum total saponins and kiwi fruit juice is: 150g: 1g: 200g.

[0012] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the kiwi fruit juice is obtained by depilating, squeezing, filtering and sterilizing fresh fruits of Actinidia chinensis Planch., a plant of the genus Actinidia in the family Actiniaceae.

[0013] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the total saponins of Gynostemma pentaphyllum are extracted from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak. and refined.

[0014] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the total glycosides of Gynostemma pentaphyllum are extracted from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak. and refined, and the total glycosides contained in it, calculated as Gynostemma pentaphyllum saponin A, are not less than 70.0%.

[0015] According to any one of the first aspects of the present invention, the Danlan Tongluo oral liquid, wherein the total glycosides of Gynostemma pentaphyllum are extracted from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak. and purified, and the total glycosides contained in the Danlan Tongluo oral liquid as Gynostemma pentaphyllum saponin A is not less than 70.0% as determined by the following method: Preparation of reference solution: Accurately weigh an appropriate amount of Gynostemma pentaphyllum saponin A reference substance dried at 60°C under reduced pressure below 2.67 KPa for 3 hours, dissolve in methanol, and prepare a solution containing 2 mg per 1 ml; Preparation of test solution: Accurately weigh 50 mg of total saponins of Gynostemma pentaphyllum, dissolve in methanol to make a solution containing 2 mg per 1 ml; Determination method: Accurately pipette 100μl of reference solution and test solution respectively, place them in 15ml stoppered test tubes, accurately add 2ml of a freshly prepared mixture of 5% vanillin glacial acetic acid solution and perchloric acid (2:8), shake well, seal, heat in a 60℃ water bath for 15 minutes, take out, immediately put into ice water to cool for 2 minutes, accurately add 10ml of glacial acetic acid, shake well, use the reagent as blank, and test according to the UV-visible spectrophotometry, measure the absorbance at a wavelength of 555±5nm, calculate the content of total glycosides as gypenosapone A based on the dry product.

[0016] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the total saponins of Gynostemma pentaphyllum are light yellowish white to light yellow powder; have a slight odor, and taste slightly bitter and sweet; are easily soluble in water and methanol, are almost insoluble in ether and chloroform, and are insoluble in petroleum ether. All items meet the requirements of the standard.

[0017] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, wherein the total saponins of Gynostemma pentaphyllum are determined by the following method, in the chromatogram of the test sample, spots of the same color and fluorescent spots appear at the corresponding positions of the chromatogram of the reference sample: Take total saponins of Gynostemma pentaphyllum and dissolve them in methanol to prepare a solution containing 10 mg per 1 ml, which is used as the test solution. Take Gynostemma pentaphyllum saponin A reference substance and dissolve it in methanol to prepare a solution containing 1 mg per 1 ml, which is used as the reference substance solution. According to the thin layer chromatography test, take 2 μl of the test solution and the reference substance solution, and spot them on the same silica gel G thin layer plate, respectively, and use chloroform-ethyl acetate-methanol-water (15:40:22:10) placed below 10°C as the lower layer solution as the developing agent, develop, develop at a distance of 12 cm, take out, dry, spray with 10% sulfuric acid ethanol solution, blow with hot air until the spots are clearly colored, and inspect under sunlight and ultraviolet light (365nm).

[0018] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, wherein the total saponins of Gynostemma pentaphyllum are determined by the following method, in the chromatogram of the test sample, spots of the same color and fluorescent spots appear at the corresponding positions of the chromatogram of the reference sample: Take 50 mg of total saponins of Gynostemma pentaphyllum, add 50 ml of 45% ethanol solution containing 7% sulfuric acid to dissolve, reflux in a water bath for 1 hour, cool, extract twice with petroleum ether (30-60℃), 50 ml each time, combine the extracts, add 30 ml of water to wash, evaporate the petroleum ether, and dissolve the residue in 1 ml of methanol as the test solution. Take another ginsengdiol reference substance, dissolve it in methanol, and make a solution containing 1 mg per 1 ml as the reference substance solution. According to the thin layer chromatography test, take 5 μl of the test solution and the reference substance solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-ether (1:1) as the developing agent, develop, develop, and develop at a distance of 12 cm, take out, dry, spray with 10% sulfuric acid ethanol solution, blow with hot air until the spots are clearly colored, and inspect under sunlight and ultraviolet light (365nm).

[0019] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the total saponins of Gynostemma pentaphyllum are dried to constant weight at 105° C. according to the drying loss determination method, and the weight loss does not exceed 5.0%.

[0020] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the residue left by the total saponins of Gynostemma pentaphyllum is not more than 1.5% when tested by the residue on ignition test method.

[0021] According to any one of the first aspects of the present invention, the Danlan Tongluo oral liquid is prepared using the following materials in the following proportions per 1000ml: 150g of Danshen, 1g of total saponins of Gynostemma pentaphyllum, 200g of kiwi fruit juice, an appropriate amount of flavoring agent, and an appropriate amount of water to 1000ml. For example, the flavoring agent is sucrose (for example, an amount of 100-150g / 1000ml oral liquid, for example, an amount of 120g / 1000ml oral liquid) or stevioside (for example, an amount of 200-500mg / 1000ml oral liquid, for example, an amount of 300mg / 1000ml oral liquid).

[0022] According to any one of the first aspects of the present invention, the Danlan Tongluo oral liquid further contains calcium lactate, for example, 1-10 g of calcium lactate is added to every 1000 ml of the oral liquid, for example, 2.5-6 g of calcium lactate is added to every 1000 ml of the oral liquid.

[0023] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps: (1) 150 g of Danshen was decocted with water three times, decocted for 2-2.5 hours with 6-8 times the amount of water for the first time, decocted for 1.5-2 hours with 6 times the amount of water for the second time, and decocted for 1.5 hours with 4-5 times the amount of water for the third time, the decoctions were combined, filtered, and the filtrate was concentrated to a concentrated solution with a relative density of 1.27-1.35 (40-50° C.); (2a) Take 1 g of total saponins of Gynostemma pentaphyllum, dissolve it in water and set aside; take another 120 g of sucrose to make syrup, combine it with the above concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral solution; or, (2b) Take 1 g of total saponins of Gynostemma pentaphyllum and 300 mg of stevioside, dissolve them in water, combine them with the above concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min), and obtain sugar-free Danlan Tongluo oral liquid.

[0024] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex1): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 8 times the amount of water for 2 hours for the first time, add 6 times the amount of water for 1.5 hours for the second time, and add 4 times the amount of water for 1.5 hours for the third time, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain the sugar-containing Danlan Tongluo oral liquid.

[0025] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex2): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300mg of stevioside, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 8 times the amount of water for 2 hours for the first time, add 6 times the amount of water for 1.5 hours for the second time, and add 4 times the amount of water for 1.5 hours for the third time, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0026] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex3): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 7 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain the sugar-containing Danlan Tongluo oral liquid.

[0027] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex4): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300mg of stevioside, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 7 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0028] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex5): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 6 times the amount of water for the first time and decoct for 2.5 hours, add 6 times the amount of water for the second time and decoct for 2 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain the sugar-containing Danlan Tongluo oral liquid.

[0029] According to any one of the first aspects of the present invention, each 1000 ml of the Danlan Tongluo oral liquid is prepared according to a method comprising the following steps (ex6): prescription: 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300mg of stevioside, appropriate amount of water to 1000ml; Preparation method: Take 150g of Danshen and add water to decoct three times, add 6 times the amount of water for the first time and decoct for 2.5 hours, add 6 times the amount of water for the second time and decoct for 2 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0030] According to the Danlan Tongluo oral liquid according to any one of the first aspects of the present invention, the calcium lactate is added together with the total saponins of Gynostemma pentaphyllum.

[0031] The Danlan Tongluo oral liquid according to any one of the first aspects of the present invention is a light brown to brown liquid with a special aroma and a sweet and sour taste.

[0032] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, it is identified by the following method: in the chromatogram of the test sample, a fluorescent spot of the same color appears at a position corresponding to the chromatogram of the control medicinal material: Take 20ml of this product, add dilute hydrochloric acid to adjust the pH to 2, add 20ml of ethyl acetate, shake well to extract, evaporate the extract on a water bath, add 1ml of methanol to the residue to dissolve it as the test solution. Take another 0.5g of Danshen control medicinal material, add appropriate amount of water, decoct for half an hour, filter, add water to the filtrate to 10ml, and prepare the control medicinal material solution in the same way. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5μl of the above control medicinal material solution and 10μl of the test solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-acetone-formic acid (25:10:4) as the developing agent, develop, take out, dry, fumigate with concentrated ammonia solution for 3 minutes, and inspect under ultraviolet light (365nm).

[0033] According to any one of the first aspects of the present invention, the Danlan Tongluo oral liquid is identified by the following method: in the chromatogram of the test sample, a fluorescent spot of the same color appears at the corresponding position of the reference sample. Take 50 ml of this product, steam it in a water bath until it is almost dry, add 50 ml of 45% ethanol solution containing 7% sulfuric acid to dissolve the residue, reflux in a water bath for 1 hour, cool, extract twice with petroleum ether (30~60℃), 50 ml each time, combine the extracts, add 30 ml of water to wash, evaporate the petroleum ether solution, and dissolve the residue in 1 ml of methanol as the test solution. Take another ginsengdiol reference substance, add methanol to make a solution containing 1 mg per 1 ml, as the reference solution. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5 μl of the above test and reference solutions, respectively, and spot them on the same silica gel G plate, use chloroform-ether (1:1) as the developing agent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, heat at 105℃ until the spots are clearly colored, and inspect under ultraviolet light (365nm).

[0034] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the relative density is 1.01~1.10 when measured according to the method recorded in 0601 of the Fourth General Rules of the Chinese Pharmacopoeia 2020 Edition.

[0035] According to the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention, the pH value is within the range of 3.0 to 4.5 when measured according to the method recorded in General Rules 0631 of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0036] According to any one of the first aspects of the present invention, the Danlan Tongluo oral liquid uses the following HPLC method to determine the content of protocatechuic aldehyde, and each 1 ml contains more than 20 μg of protocatechuic aldehyde: Determined by high performance liquid chromatography according to the general rule 0512 of Part IV of the 2020 edition of the Chinese Pharmacopoeia; Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as filler, methanol-0.04% glacial acetic acid (16:84) was used as mobile phase, and the detection wavelength was 280nm; the theoretical plate number calculated based on the protocatechuic aldehyde peak should be no less than 2500; Preparation of reference solution: accurately weigh 10 mg of protocatechuic aldehyde reference substance, place it in a 50 ml volumetric flask, dissolve it with methanol and dilute it to the mark, shake well; accurately pipette 1 ml, place it in a 10 ml volumetric flask, add methanol to dilute it to the mark, shake well, and the solution is ready; Preparation of test solution: accurately pipette 2.0 ml of Danlan Tongluo oral solution into a 10 ml volumetric flask, add methanol to the mark, shake thoroughly, let stand for 30 minutes, pipette the above clear solution, filter with a microporous filter membrane (0.45 μm), discard the initial filtrate, and take the subsequent filtrate to obtain; Determination method: Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0037] Furthermore, the second aspect of the present invention provides a method for preparing the Danlan Tongluo oral liquid according to any one of the first aspects of the present invention, and the preparation of each 1000 ml of the Danlan Tongluo oral liquid comprises the following steps: (1) 150 g of Danshen was decocted with water three times, decocted for 2-2.5 hours with 6-8 times the amount of water for the first time, decocted for 1.5-2 hours with 6 times the amount of water for the second time, and decocted for 1.5 hours with 4-5 times the amount of water for the third time, the decoctions were combined, filtered, and the filtrate was concentrated to a concentrated solution with a relative density of 1.27-1.35 (40-50° C.); (2a) Take 1 g of total saponins of Gynostemma pentaphyllum, dissolve it in water and set aside; take another 120 g of sucrose to make syrup, combine it with the above concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral solution; or, (2b) Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain sugar-free Danlan Tongluo oral liquid. For example, 1-10g, for example 2.5-6g of calcium lactate is added to the total saponins of Gynostemma pentaphyllum.

[0038] Furthermore, the third aspect of the present invention provides the use of the Danlan Tongluo oral liquid described in any one of the first aspects of the present invention in the preparation of a medicine having the effects of removing blood stasis, unblocking meridians, invigorating qi and regulating the middle, or in the preparation of a medicine for improving palpitations, chest tightness, fatigue, shortness of breath, insomnia and loss of appetite caused by deficiency of both qi and blood.

[0039] As described in the context of the present invention, the Danlan Tongluo oral liquid of the present invention exhibits one or more beneficial effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 : HPLC chromatogram of protocatechuic aldehyde reference substance.

[0041] Figure 2 : The HPLC chromatogram of embodiment 1 Danlan Tongluo oral liquid. DETAILED DESCRIPTION

[0042] The present invention can be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be appreciated by those skilled in the art that various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention. The present invention provides general and / or specific descriptions of the materials and test methods used in the test. Although many materials and operating methods used to achieve the purpose of the present invention are well known in the art, the present invention is still described in as much detail as possible at this point.

[0043] Raw material 1: Gynostemma pentaphyllum total saponins The total saponins of Gynostemma pentaphyllum used in Danlan Tongluo oral liquid are extracted from the whole herb of the gourd root plant Gynosstemmapentaphyllum (Thunb.) Mak. and refined. They are also commonly called total glycosides of Gynostemma pentaphyllum, total saponins of Gynostemma pentaphyllum, and total glycosides of Gynostemma pentaphyllum. The total saponins of Gynostemma pentaphyllum are easily purchased from channels approved by the national drug regulatory authorities (https: / / www.nmpa.gov.cn / datasearch / search-result.html). If not otherwise specified, when preparing Danlan Tongluo oral liquid in the present invention, the total saponins of Gynostemma pentaphyllum used are obtained from commercial sources (purchased from Ankang Beiyi University Pharmaceutical Co., Ltd., lot221026), and their quality meets the standard WS3-Z-006-93 (Z) of total saponins of Gynostemma pentaphyllum. The results of the standardized testing of the above-mentioned total saponins of Gynostemma pentaphyllum in accordance with this standard and the 2020 edition of the Chinese Pharmacopoeia are as follows: 1. Properties: Light yellowish white to light yellow powder; slight odor, slightly bitter and sweet taste; easily soluble in water and methanol, almost insoluble in ether and chloroform, and insoluble in petroleum ether. All items meet the requirements of the standard.

[0044] 2. Identification a: Take total saponins of Gynostemma pentaphyllum and dissolve them in methanol to make a solution containing 10 mg per 1 ml as the test solution. Take Gynostemma pentaphyllum saponin A reference substance (purchased from the China Inspection Institute) and dissolve it in methanol to make a solution containing 1 mg per 1 ml as the reference solution. According to the thin layer chromatography test, take 2 μl of the test solution and the reference solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-ethyl acetate-methanol-water (15:40:22:10) placed below 10°C as the developing agent, develop, spread 12 cm, take out, dry, spray with 10% sulfuric acid ethanol solution, blow with hot air until the spots are clearly colored, and inspect under sunlight and ultraviolet light (365nm). In the chromatogram of the test product, spots of the same color and fluorescent spots appear at the corresponding positions of the chromatogram of the reference substance. The test results meet the requirements.

[0045] 3. Identification b: Take 50 mg of total saponins of Gynostemma pentaphyllum, add 50 ml of 45% ethanol solution containing 7% sulfuric acid to dissolve, reflux in a water bath for 1 hour, cool, extract twice with petroleum ether (30-60℃), 50 ml each time, combine the extracts, add 30 ml of water to wash, evaporate the petroleum ether, and dissolve the residue in 1 ml of methanol as the test solution. Take another ginsengdiol reference substance, add methanol to dissolve, and make a solution containing 1 mg per 1 ml as the reference substance solution. According to the thin layer chromatography test, take 5 μl of the test solution and the reference substance solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-ether (1:1) as the developing agent, develop, develop, and develop at a distance of 12 cm, take out, dry, spray with 10% sulfuric acid ethanol solution, blow with hot air until the spots are clearly colored, and inspect under sunlight and ultraviolet light (365nm). In the chromatogram of the test sample, spots of the same color and fluorescent spots appear at the corresponding positions of the chromatogram of the reference sample. The test results meet the requirements.

[0046] 4. Loss on drying: Take an appropriate amount of this product and dry it at 105°C to constant weight according to the loss on drying method. The loss of weight shall not exceed 5.0%. The actual measured result is 1.22%.

[0047] 5. Residue on ignition: Take 1.0g of this product and check it according to the residue on ignition test method. The residue left shall not exceed 1.5%. The actual measured result is 0.37%.

[0048] 6. Content determination: Preparation of reference solution: Accurately weigh an appropriate amount of Gynostemma pentaphyllum saponin A reference substance dried at 60°C under reduced pressure below 2.67 KPa for 3 hours, dissolve in methanol, and prepare a solution containing 2 mg per 1 ml; Preparation of test solution: Accurately weigh 50 mg of the product and dissolve it in methanol to make a solution containing 2 mg per 1 ml; Determination method: Accurately pipette 100μl of reference solution and test solution respectively, place them in 15ml stoppered test tubes, accurately add 2ml of the newly prepared mixture of 5% vanillin glacial acetic acid solution and perchloric acid (2:8), shake well, seal, heat in a 60℃ water bath for 15 minutes, take out, immediately put into ice water to cool for 2 minutes, accurately add 10ml of glacial acetic acid, shake well, use the reagent as blank, test according to the UV-Vis spectrophotometry, measure the absorbance at a wavelength of 555±5nm, and calculate to obtain; this product is calculated on the basis of the dry product, and the total glycosides contained in this product, calculated as gypenosyl saponin A (C53H90O21), shall not be less than 70.0%; the actual measured result is 84.6%.

[0049] 7. Microbial limit: Take this product and inspect it according to the microbial limit test method for non-sterile products. It is usually required that the total aerobic bacteria count of the product shall not exceed 50 cfu / ml, the total mold and yeast count shall not exceed 10 cfu / ml, and Escherichia coli shall not be detected. The total aerobic bacteria count was determined to be <5 cfu / ml, the total mold and yeast count was <1 cfu / ml, and Escherichia coli was not detected.

[0050] Ingredient 2: Kiwi juice The kiwifruit juice used in Danlan Tongluo oral liquid is obtained by depilating, juicing, filtering and sterilizing the fresh fruit of kiwifruit Actinidiachinensis Planch. of the Actinidia genus of the Actinidia family. If not otherwise specified, when preparing Danlan Tongluo oral liquid in the present invention, the kiwifruit juice used is homemade by the applicant, and the preparation method is as follows: take the ripe fresh fruits picked in late September, wash and depilate 3 times, treat with purified water for the last time, drain the water, squeeze the juice, filter with 40 mesh, 120 mesh and 200 mesh stainless steel filter screens in turn, sterilize the filtrate at 110°C for 15min, seal and package, and store in a cool place at 2~6°C for standby use (retest period is 6 months, validity period is 12 months). This preparation method does not contain any additives and is a conventional preparation method for medicinal kiwifruit juice. Inspection and results: 1. Properties: This product is a light brown to brown liquid with a special kiwi aroma and a sweet and sour taste. 2. Microbial limit: Take this product and inspect it according to the microbial limit test method for non-sterile products. It is usually required that the total aerobic bacteria count of the product shall not exceed 100 cfu / ml, the total mold and yeast count shall not exceed 50 cfu / ml, and Escherichia coli shall not be detected / ml. The total aerobic bacteria count was determined to be <10 cfu / ml, the total mold and yeast count was <5 cfu / ml, and Escherichia coli was not detected.

[0051] When preparing Danlan Tongluo oral liquid in the present invention, other materials such as sucrose, stevioside, water and the like are used in accordance with the medicinal requirements of the oral liquid. Various reference substances or reference medicinal materials used in various tests of the present invention are purchased from the China Food and Drug Inspection Institute unless otherwise specified, and of course other commercial sources can also be easily obtained.

[0052] Salvia miltiorrhiza is the dried root of the plant of the genus Salvia of the family Lamiaceae. The Salvia miltiorrhiza used in the specific experiment of the present invention was purchased from the Anguo medicinal material market in Hebei Province, and was tested according to the method under the Salvia miltiorrhiza item in Part I of the 2020 edition of the Chinese Pharmacopoeia, which complies with the provisions of the Pharmacopoeia.

[0053] Example 1: Preparation of Danlan Tongluo Oral Liquid (Sugar-containing Type) The prescription and preparation method of this embodiment refer to national drug standards.

[0054] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose and appropriate amount of water to 1000ml.

[0055] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 8 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 4 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (91.2g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral liquid.

[0056] Example 2: Preparation of Danlan Tongluo Oral Liquid (Sugar-free) The prescription and preparation method of this embodiment refer to national drug standards.

[0057] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300 mg of stevioside and appropriate amount of water to 1000 ml.

[0058] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 8 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 4 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (90.6g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0059] Test Example 1: Quality index testing of sugar-containing and sugar-free Danlan Tongluo oral liquid This test example refers to the national drug standard WS-5702 (B-0702)-2014Z to test the quality indicators of the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Example 1 and Example 2. The Danlan Tongluo oral liquids obtained in other embodiments of the present invention can also be tested using the method of this test example.

[0060] 1. Properties: The standard stipulates that Danlan Tongluo oral liquid is also a light brown to brown liquid with a special aroma and a sweet and sour taste. Upon inspection, the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Example 1 and Example 2 are both light brown to brown liquids with a special aroma and a sweet and sour taste.

[0061] 2. Identification a: Take 20ml of this product, add dilute hydrochloric acid to adjust the pH value to 2, add 20ml of ethyl acetate, shake well to extract, place the extract on a water bath to evaporate to dryness, add 1ml of methanol to the residue to dissolve it as the test solution. Take another 0.5g of Danshen control medicinal material, add appropriate amount of water, decoct for half an hour, filter, add water to the filtrate to 10ml, and prepare the control medicinal material solution in the same way. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5μl of the above-mentioned control medicinal material solution and 10μl of the test solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-acetone-formic acid (25:10:4) as the developing agent, develop, take out, dry, fumigate with concentrated ammonia solution for 3 minutes, and inspect under ultraviolet light (365nm). The national drug standard stipulates that in the test sample chromatogram, at the position corresponding to the control medicinal material chromatogram, a fluorescent spot of the same color appears. Upon testing, in the chromatograms of the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Example 1 and Example 2, fluorescent spots of the same color appeared at positions corresponding to the chromatograms of the Danshen control medicinal material.

[0062] 3. Identification b: Take 50 ml of this product, steam it in a water bath until it is almost dry, add 50 ml of 45% ethanol solution containing 7% sulfuric acid to dissolve the residue, reflux in a water bath for 1 hour, cool, extract twice with petroleum ether (30~60℃), 50 ml each time, combine the extracts, add 30 ml of water to wash, evaporate the petroleum ether solution, and dissolve the residue in 1 ml of methanol as the test solution. Take another ginsengdiol reference substance, add methanol to make a solution containing 1 mg per 1 ml, as the reference solution. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5 μl of the above test and reference solutions, respectively, and spot them on the same silica gel G plate, use chloroform-ether (1:1) as the developing agent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, heat at 105℃ until the spots are clearly colored, and inspect under ultraviolet light (365nm). The national drug standard stipulates that in the chromatogram of the test sample, at the position corresponding to the reference sample, a fluorescent spot of the same color is displayed. After testing, in the chromatograms of the test samples of the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Example 1 and Example 2, fluorescent spots of the same color are displayed at the position corresponding to the ginsenodiol reference sample.

[0063] 4. Relative density: According to the method described in 0601 of the fourth part of the 2020 edition of the Chinese Pharmacopoeia, the national drug standard stipulates that the relative density of the sugar-containing Danlan Tongluo oral liquid should be 1.01~1.10, and the relative density of the sugar-free Danlan Tongluo oral liquid should be 1.01~1.10. After testing, the relative densities of the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Example 1 and Example 2 were 1.037 and 1.022, respectively.

[0064] 5. pH value: According to the method described in 0631 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia, the national drug standard stipulates that the pH value of Danlan Tongluo oral liquid should be in the range of 3.0 to 4.5. After testing, the pH values ​​of the Danlan Tongluo oral liquid obtained in Example 1 and Example 2 were 3.57 and 3.71, respectively.

[0065] 6. Determination of protocatechuic aldehyde content: This determination method uses HPLC to determine the content of protocatechuic aldehyde derived from Salvia miltiorrhiza.

[0066] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0067] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as filler, methanol-0.04% glacial acetic acid (16:84) was used as mobile phase, and the detection wavelength was 280nm. The theoretical plate number calculated based on the protocatechuic aldehyde peak should be no less than 2500.

[0068] Preparation of reference solution: Accurately weigh 10 mg of protocatechuic aldehyde reference substance, place it in a 50 ml volumetric flask, dissolve it with methanol and dilute it to the mark, shake well. Accurately pipette 1 ml, place it in a 10 ml volumetric flask, add methanol to dilute it to the mark, shake well, and you have it.

[0069] Preparation of test solution: Accurately pipette 2.0 ml of Danlan Tongluo oral liquid into a 10 ml volumetric flask, add methanol to the mark, shake thoroughly, let stand for 30 minutes, pipette the above clear liquid, filter with a microporous filter membrane (0.45 μm), discard the initial filtrate, and take the subsequent filtrate.

[0070] Determination method: Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0071] The national drug standard stipulates that the content of protocatechuic aldehyde (C7H6O3) in each 1ml of Danlan Tongluo oral liquid must not be less than 20μg.

[0072] After testing, the protocatechuic aldehyde contents of the Danlan Tongluo oral liquids obtained in Example 1 and Example 2 were 113.2 μg / ml and 107.4 μg / ml, respectively.

[0073] Typical HPLC graphs are shown in Figure 1 (Chromatogram of protocatechuic aldehyde reference substance) and Figure 2 (Chromatogram of Danlan Tongluo oral liquid of Example 1).

[0074] 7. Determination of the content of Gynostemma saponin A: Given that the quality control of gypenosides mainly involves the monitoring of the content of gypenosides A, and the existing Danlantongluo oral liquid preparations do not monitor the content of gypenosides A, especially whether the preparations will change during long-term storage, it is necessary to monitor the content of gypenosides A in the Danlantongluo oral liquid preparations.

[0075] Preparation of reference solution: Accurately weigh an appropriate amount of Gynostemma pentaphyllum saponin A reference substance dried at 60°C under reduced pressure below 2.67 KPa for 3 hours, dissolve in methanol, and prepare a solution containing 2 mg per 1 ml; Preparation of test solution: accurately pipette 10 ml of Danlan Tongluo oral liquid, evaporate to dryness under reduced pressure at 60°C, add 5 ml of methanol to dissolve the residue to prepare the test solution; Determination method: Accurately pipette 100μl of reference solution and test solution, respectively, into 15ml stoppered test tubes, accurately add 2ml of a newly prepared mixture of 5% vanillin glacial acetic acid solution and perchloric acid (2:8), shake well, seal tightly, heat in a 60℃ water bath for 15 minutes, take out, immediately put into ice water to cool for 2 minutes, accurately add 10ml of glacial acetic acid, shake well, use the reagent as a blank, test according to the UV-visible spectrophotometry method, measure the absorbance at a wavelength of 555±5nm, and calculate the content of Gynostemma Saponin A. According to the amount of Gynostemma Saponin and the content of Gynostemma Saponin A in Gynostemma Saponin, the theoretical concentration of Gynostemma Saponin A in the prepared oral solution should be 0.846mg / ml.

[0076] After testing, the contents of gypenoside A in the Danlan Tongluo oral liquid obtained in Example 1 and Example 2 were 844.3 μg / ml and 841.8 μg / ml, respectively, indicating that there was substantially no loss of gypenoside A during the preparation process.

[0077] Example 3: Preparation of Danlan Tongluo Oral Liquid (Sugar-containing Type) This example basically prepares Danlan Tongluo oral liquid with reference to the prescription and preparation method of Example 1.

[0078] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose and appropriate amount of water to 1000ml.

[0079] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 7 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (89.4g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral liquid.

[0080] Example 4: Preparation of Danlan Tongluo Oral Liquid (Sugar-free Type) This embodiment basically prepares Danlan Tongluo oral liquid with reference to the prescription and preparation method of Example 2.

[0081] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300 mg of stevioside and appropriate amount of water to 1000 ml.

[0082] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 7 times the amount of water for the first time and decoct for 2 hours, add 6 times the amount of water for the second time and decoct for 1.5 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (91.7g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0083] Example 5: Preparation of Danlan Tongluo Oral Liquid (Sugar-containing Type) This example basically prepares Danlan Tongluo oral liquid with reference to the prescription and preparation method of Example 1.

[0084] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 120g sucrose and appropriate amount of water to 1000ml.

[0085] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 6 times the amount of water for the first time and decoct for 2.5 hours, add 6 times the amount of water for the second time and decoct for 2 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (90.3g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum, add water to dissolve, and set aside; take another 120g of sucrose to make syrup, combine it with the above-mentioned concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral liquid.

[0086] Example 6: Preparation of Danlan Tongluo Oral Liquid (Sugar-free) This embodiment basically prepares Danlan Tongluo oral liquid with reference to the prescription and preparation method of Example 2.

[0087] Prescription (preparation 1000ml): 150g of Danshen, 1g of Gynostemma pentaphyllum total saponins, 200g of kiwi fruit juice, 300 mg of stevioside and appropriate amount of water to 1000 ml.

[0088] Preparation method (preparation of 1000ml): Take 150g of Danshen and add water to decoct three times, add 6 times the amount of water for the first time and decoct for 2.5 hours, add 6 times the amount of water for the second time and decoct for 2 hours, add 5 times the amount of water for the third time and decoct for 1.5 hours, combine the decoctions, filter, and concentrate the filtrate to a concentrate (92.2g) with a relative density of 1.27~1.35 (40~50℃); Take 1g of total saponins of Gynostemma pentaphyllum and 300mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000ml, mix well, filter (0.45µm microporous filter membrane), fill (10ml / bottle), and sterilize (115°C, 20min) to obtain the sugar-free Danlan Tongluo oral liquid.

[0089] Test Example 2: Quality Index Testing of Danlan Tongluo Oral Liquid The quality indicators of the sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 were measured using the method of Test Example 1 of the present invention, and the results are as follows.

[0090] 1. Properties: The four sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 are all light brown to brown liquids with a special aroma and a sweet and sour taste.

[0091] 2. Identification a: In the chromatograms of the four sugar-containing and sugar-free Danlan Tongluo oral liquid test samples obtained in Examples 3-6, fluorescent spots of the same color appeared at the positions corresponding to the chromatograms of the Danshen control medicinal material.

[0092] 3. Identification b: In the chromatograms of the four sugar-containing and sugar-free Danlan Tongluo oral liquid test samples obtained in Examples 3-6, fluorescent spots of the same color appeared at the positions corresponding to those of the ginsenodiol reference substance.

[0093] 4. Relative density: The relative densities of the four sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 were 1.041, 1.026, 1.036 and 1.031, respectively.

[0094] 5. pH value: The pH values ​​of the four sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 were 3.63, 3.57, 3.75 and 3.68, respectively.

[0095] 6. Determination of protocatechuic aldehyde content: The protocatechuic aldehyde contents of the four sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 were 108.4 μg / ml, 115.7 μg / ml, 105.8 μg / ml, and 112.6 μg / ml, respectively.

[0096] 7. Determination of the content of gypenosin A: The contents of gypenosin A in the four sugar-containing and sugar-free Danlan Tongluo oral liquids obtained in Examples 3-6 were 843.7 μg / ml, 848.2 μg / ml, 841.7 μg / ml, and 845.2 μg / ml, respectively.

[0097] The above results show that the various inspection indicators of the Danlan Tongluo oral liquid obtained in Examples 3-6 are basically the same as those in Examples 1-2.

[0098] Danlan Tongluo oral liquid has been used clinically for many years. For a long time, the national drug standards mainly monitor the content of protocatechuic aldehyde. Although protocatechuic aldehyde is relatively stable during the long-term storage of the oral liquid, the inventors found that the content of gypenosin A changes during the long-term storage of the oral liquid when conducting in-depth research on the product. The inventors have unexpectedly found that adding calcium lactate to the oral liquid helps to improve the stability of gypenosin A during long-term storage, and the addition of calcium lactate can only play the effect of improving the stability of gypenosin A when it is greater than 2.5g / L. However, when the addition of calcium lactate is greater than 6g / L, the pH value of the liquid increases significantly after stability treatment, indicating that the addition of calcium lactate is preferably within the range of 2.5~6g / L. The specific test is shown below.

[0099] Example 7: Preparation of Danlan Tongluo Oral Liquid Referring to the prescriptions and preparation methods of Examples 1-6 respectively, the only difference is that 3.5 g of calcium lactate (equivalent to a concentration of 3.5 g / 1000 ml) is also added when Gynostemma saponin A is added, and 6 batches of oral liquid are obtained, which can be respectively recorded as Example 71, Example 72, ... Example 76 oral liquid.

[0100] Example 8: Preparation of Danlan Tongluo Oral Liquid (Sugar-Containing Type) Referring to the prescription and preparation method of Example 1, the only difference is that 0g, 0.5g, 1.5g, 2.5g, 3.5g, 5g, 6g, 8g (8g / L), and 10g (10g / L) calcium lactate are added together with Gynostemma saponin A to obtain 9 batches of oral liquid, which can be respectively recorded as Example 81, Example 82, ... Example 89 oral liquid.

[0101] Example 9: Preparation of Danlan Tongluo Oral Liquid (Sugar-free) Referring to the prescription and preparation method of Example 2, the only difference is that 0g, 0.5g, 1.5g, 2.5g, 3.5g, 5g, 6g, 8g (8g / L), and 10g (10g / L) calcium lactate are added together with Gynostemma saponin A to obtain 9 batches of oral liquid, which can be respectively recorded as Example 91, Example 92, ... Example 99 oral liquid.

[0102] Test Example 3: Quality index detection of Danlan Tongluo oral liquid obtained in Examples 7 to 9 The quality indicators of the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 were measured using the method of Test Example 1 of the present invention, and the results were as follows.

[0103] 1. Properties: The 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 are all light brown to brown liquids with a special aroma and a sweet and sour taste.

[0104] 2. Identification a: The six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 all showed fluorescent spots of the same color in the chromatograms of the test samples at positions corresponding to those of the chromatograms of the reference medicinal material Salvia miltiorrhiza.

[0105] 3. Identification b: The 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 all showed fluorescent spots of the same color at the positions corresponding to those of the ginsenodiol reference substance in the chromatograms of the test samples.

[0106] 4. Relative density: The relative density of the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 are all within the range of 1.01 to 1.04. For example, the relative density of the oral liquid in Example 71 is 1.034.

[0107] 5. pH value: The pH values ​​of the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 were all within the range of 3.5 to 4.0. For example, the pH value of the oral liquid in Example 71 was 3.73.

[0108] 6. Determination of protocatechuic aldehyde content: The protocatechuic aldehyde content of the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 were all within the range of 104-116 μg / ml. For example, the protocatechuic aldehyde content of the oral liquid in Example 71 was 107.9 μg / ml.

[0109] 7. Determination of the content of gypenoside A: The 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 all had gypenoside A contents in the range of 836-853 μg / ml. For example, the oral liquid in Example 71 was 847.2 μg / ml.

[0110] The above results show that the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 have substantially the same inspection indicators as those of Examples 1-2.

[0111] Test Example 4: Stability Study of Danlan Tongluo Oral Liquid Stability investigation method: The sugar-containing or sugar-free Danlan Tongluo oral liquid prepared in various embodiments of the present invention is packaged in commercial packaging (soda-lime glass tube oral liquid bottle), 10 ml per bottle, and placed in a dark place at 45°C for 5 months (which can be called high temperature 5 months). The quality indicators of the sugar-containing and sugar-free Danlan Tongluo oral liquid under investigation are determined according to the method of Test Example 1 of the present invention in October and May, respectively.

[0112] The 6 oral liquids obtained in Examples 1 to 6, the 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 were subjected to the above-mentioned high temperature stability study for 5 months. Their 0-month results are as described in Test Examples 1 to 3 above, and there is no obvious difference in the quality indicators of the oral liquids of various formulas (sugar-containing or sugar-free, with or without calcium lactate, with more or less calcium lactate).

[0113] After these oral solutions were treated at high temperature for 5 months, there were significant differences in pH value and gypenoside A content among different formulations, while there were no significant differences in other quality indicators, as follows: 1. Properties: When the temperature was high for 5 months, the six oral liquids obtained in Examples 1 to 6, the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 were all light brown to brown liquids with a special aroma; the sour-sweet taste of the six oral liquids in Examples 87 to 89 and Examples 7 to 99 became significantly weaker, and the remaining oral liquids all showed a sour-sweet taste.

[0114] 2. Identification a: At high temperature for 5 months, the 6 oral liquids obtained in Examples 1 to 6, the 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 all showed fluorescent spots of the same color in the chromatograms of the test samples at positions corresponding to those of the chromatograms of the control medicinal material Salvia miltiorrhiza.

[0115] 3. Identification b: At high temperature for 5 months, the 6 oral liquids obtained in Examples 1 to 6, the 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 all showed fluorescent spots of the same color in the chromatograms of the test samples at the positions corresponding to those of the ginsenodiol reference substance.

[0116] 4. Relative density: At high temperature for 5 months, the relative densities of the six oral liquids obtained in Examples 1 to 6, the six oral liquids obtained in Example 7, the nine oral liquids obtained in Example 8, and the nine oral liquids obtained in Example 9 were all within the range of 1.02 to 1.05. For example, the relative densities of the oral liquid in Example 1 and the oral liquid in Example 71 were 1.036 and 1.028, respectively.

[0117] 5. Determination of protocatechuic aldehyde content: At high temperature for 5 months, the 6 oral liquids obtained in Examples 1 to 6, the 6 oral liquids obtained in Example 7, the 9 oral liquids obtained in Example 8, and the 9 oral liquids obtained in Example 9 all had protocatechuic aldehyde contents within the range of 105 to 117 μg / ml. For example, the protocatechuic aldehyde contents of the oral liquid in Example 1 and the oral liquid in Example 71 were 111.4 μg / ml and 107.3 μg / ml, respectively, and the results of each sample were substantially indistinguishable from the results in 0 month.

[0118] 6. pH value: At high temperature for 5 months, the pH values ​​of the 6 oral liquids obtained in Examples 1 to 6, the 6 oral liquids obtained in Example 7, the 6 oral liquids obtained in Examples 81 to 86, and the 6 oral liquids obtained in Examples 81 to 86 were all within the range of 3.5 to 4.1. For example, the pH values ​​of the oral liquids in Example 71, Example 86, and Example 96 were 3.84, 4.04, and 4.07, respectively, and the differences from their respective pH values ​​at 0 months were all less than ±0.18 pH units. The pH values ​​of the three oral solutions with added calcium lactate greater than 6 g / L in Examples 87 to 89 were 5.11, 5.35 and 5.74, respectively, which were 1.42, 1.55 and 1.93 pH units higher than their respective pH values ​​at 0 month; the pH values ​​of the three oral solutions with added calcium lactate greater than 6 g / L in Examples 97 to 99 were 5.02, 5.33 and 5.64, respectively, which were 1.36, 1.61 and 1.87 pH units higher than their respective pH values ​​at 0 month.

[0119] 7. Determination of the content of gypenosin A: The content of gypenosin A in the oral liquid obtained in each example at high temperature for 5 months was determined. For a certain oral liquid, the residual rate of gypenosin A at high temperature for 5 months relative to that at 0 month (determined above) was calculated using the following formula: Oral liquid high temperature May Gynostemma pentaphyllum saponin A residual rate = (May content ÷ 0 month content) × 100% It was determined that the residual rates of gypenosin A in the six oral liquids of Example 7 with 3.5 g / 1000 ml of calcium lactate added were all within the range of 98% to 101%, for example, the residual rate of gypenosin A in the oral liquid of Example 71 was 99.2%; the residual rates of gypenosin A in the six oral liquids of Examples 84 to 89 with an amount of calcium lactate greater than 2.5 g / L were all within the range of 97% to 101%, for example, the residual rates of gypenosin A in the oral liquids of Examples 84 and 89 were 97.8% and 99.6%, respectively; the residual rates of gypenosin A in the six oral liquids of Examples 94 to 99 with an amount of calcium lactate greater than 2.5 g / L were all within the range of 97% to 101%. % range, for example, the residual rates of Gynostemma saponin A of the oral liquids of Example 94 and Example 99 are 97.3% and 99.2%, respectively; the residual rates of Gynostemma saponin A of the 8 oral liquids without calcium lactate of Examples 1 to 6, Example 81, and Example 91 are all within the range of 82% to 85%, for example, the residual rate of Gynostemma saponin A of the oral liquid of Example 81 is 83.8%; the residual rates of Gynostemma saponin A of the oral liquids of Example 82 and Example 92 with added calcium lactate 0.5 g / L are 86.8% and 87.4%, respectively; the residual rates of Gynostemma saponin A of the oral liquids of Example 83 and Example 93 with added calcium lactate 1.5 g / L are 91.2% and 90.6%, respectively.

[0120] The above results show that adding an appropriate amount of calcium lactate helps to improve the stability of gypenoside A in the oral solution, but excessive addition will cause the pH stability of the oral solution to deteriorate. The addition amount of calcium lactate is preferably in the range of 2.5-6 g / L, especially 2.5-5 g / L.

[0121] In view of the fact that some of the oral liquids prepared in the present invention exhibit better stability, it can be expected that they have better biological properties.

[0122] The above is a detailed description of the spirit of the present invention through the preferred embodiments of the present invention. Those skilled in the art understand that any modification, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention fall within the protection scope of the present invention.

Claims

1. A Danlan Tongluo oral liquid, which is prepared from salvia miltiorrhiza, total saponins of gynostemma pentaphyllum, kiwi fruit juice and pharmaceutically acceptable excipients.

2. According to the Danlan Tongluo oral liquid of claim 1, the weight ratio of Danshen, Gynostemma pentaphyllum total saponins and kiwi fruit juice is: 150g: 1g: 200g.

3. The Danlan Tongluo oral liquid according to claim 1, wherein: Kiwi fruit juice is obtained by removing hair, squeezing juice, filtering and sterilizing fresh fruit of Actinidia chinensis Planch. of Actinidiaceae. Gynostemma pentaphyllum total saponins are extracted from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak. and refined; Gynostemma pentaphyllum total saponins are obtained by extracting and refining the total glycosides from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak., and the total glycosides contained in the total saponins A are not less than 70.0%; and / or, Gynostemma pentaphyllum total saponins are extracted from the whole herb of the cucurbit root plant Gynosstemma pentaphyllum (Thunb.) Mak. and purified. The total glycosides contained in it as Gynostemma pentaphyllum saponin A are not less than 70.0% as determined by the following method: Preparation of reference solution: accurately weigh an appropriate amount of Gynostemma pentaphyllum saponin A reference substance dried at 60℃ and reduced pressure below 2.67KPa for 3 hours, dissolve it in methanol to prepare a solution containing 2 mg per 1 ml; Preparation of test solution: accurately weigh 50 mg of Gynostemma pentaphyllum total saponins, dissolve it in methanol to prepare a solution containing 2 mg per 1 ml; Determination method: Accurately pipette 100μl of reference solution and test solution respectively, place them in 15ml stoppered test tubes, accurately add 2ml of a freshly prepared mixture of 5% vanillin glacial acetic acid solution and perchloric acid (2:8), shake well, seal, heat in a 60℃ water bath for 15 minutes, take out, immediately put into ice water to cool for 2 minutes, accurately add 10ml of glacial acetic acid, shake well, use the reagent as blank, and test according to the UV-visible spectrophotometry, measure the absorbance at a wavelength of 555±5nm, calculate the content of total glycosides as gypenosapone A based on the dry product.

4. The Danlan Tongluo oral liquid according to claim 1, wherein: Gynostemma pentaphyllum total saponins are light yellow-white to light yellow powder; with a slight odor and a slightly bitter and sweet taste; easily soluble in water and methanol, almost insoluble in ether and chloroform, and insoluble in petroleum ether; Gynostemma total saponins were determined as follows: in the chromatogram of the test sample, spots of the same color and fluorescent spots appeared at the corresponding positions of the chromatogram of the reference sample: take total saponins of Gynostemma pentaphyllum and dissolve them in methanol to prepare a solution containing 10 mg per 1 ml, which was used as the test solution; take Gynostemma pentaphyllum saponin A reference substance and dissolve it in methanol to prepare a solution containing 1 mg per 1 ml, which was used as the reference solution; According to the thin layer chromatography test, take 2 μl of the test solution and the reference solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-ethyl acetate-methanol-water (15:40:22:10) placed below 10°C as the developing agent, develop, develop, spread 12 cm, take out, dry, spray with 10% sulfuric acid ethanol solution, blow with hot air until the spots are clearly colored, and examine under sunlight and ultraviolet light (365nm); Gynostemma total saponins were determined as follows. In the chromatogram of the test sample, spots of the same color and fluorescent spots appeared at the corresponding positions of the chromatogram of the reference sample: 50 mg of Gynostemma total saponins were dissolved in 50 ml of 45% ethanol solution containing 7% sulfuric acid, refluxed in a water bath for 1 hour, cooled, extracted twice with petroleum ether (30-60°C), 50 ml each time, combined the extracts, washed with 30 ml of water, evaporated the petroleum ether, and dissolved the residue with 1 ml of methanol as the test solution; separately, panaxadiol reference sample was dissolved in methanol to prepare a solution containing 1 mg per 1 ml as the reference solution; According to the thin layer chromatography test, 5 μl of the test solution and the reference solution were respectively spotted on the same silica gel G thin layer plate, and chloroform-ether (1:1) was used as the developing solvent. The plate was developed with a development distance of 12 cm. The plate was taken out and dried, and sprayed with 10% sulfuric acid ethanol solution. Hot air was blown until the spots were clearly colored, and then examined under sunlight and ultraviolet light (365 nm); The total saponins of Gynostemma pentaphyllum are dried to constant weight at 105°C according to the loss on drying method, with a weight loss of no more than 5.0%; and / or, The total saponins of Gynostemma pentaphyllum are tested by the ignition residue test method, and the remaining residue does not exceed 1.5%.

5. According to claim 1, the Danlan Tongluo oral liquid is prepared using the following materials in the following proportions per 1000ml: 150g of Salvia miltiorrhiza, 1g of total saponins of Gynostemma pentaphyllum, 200g of kiwi fruit juice, an appropriate amount of flavoring agent, and an appropriate amount of water to 1000ml; for example, the flavoring agent is sucrose (for example, an amount of 100-150g / 1000ml oral liquid, for example, an amount of 120g / 1000ml oral liquid) or stevioside (for example, an amount of 200-500mg / 1000ml oral liquid, for example, an amount of 300mg / 1000ml oral liquid); for example, calcium lactate is also added to the Danlan Tongluo oral liquid; for example, 1-10g of calcium lactate is added to every 1000ml oral liquid, for example, 2.5-6g of calcium lactate is added to every 1000ml oral liquid.

6. The Danlan Tongluo oral liquid according to claim 1, wherein each 1000 ml thereof is prepared by a method comprising the following steps: (1) 150 g of Danshen was decocted with water three times, decocted for 2-2.5 hours with 6-8 times the amount of water for the first time, decocted for 1.5-2 hours with 6 times the amount of water for the second time, and decocted for 1.5 hours with 4-5 times the amount of water for the third time, the decoctions were combined, filtered, and the filtrate was concentrated to a concentrated solution with a relative density of 1.27-1.35 (40-50° C.); (2a) Take 1 g of total saponins of Gynostemma pentaphyllum, dissolve it in water and set aside; take another 120 g of sucrose to make syrup, combine it with the above concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral solution; or, (2b) Take 1 g of total saponins of Gynostemma pentaphyllum and 300 mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain sugar-free Danlan Tongluo oral liquid; for example, the calcium lactate is added together with the total saponins of Gynostemma pentaphyllum.

7. The Danlan Tongluo oral liquid according to claim 1, wherein: It is a light brown to brown liquid with a special aroma and a sweet and sour taste; It is identified according to the following method: in the chromatogram of the test sample, a fluorescent spot of the same color appears at the position corresponding to the chromatogram of the control medicinal material: Take 20ml of this product, add dilute hydrochloric acid to adjust the pH value to 2, add 20ml of ethyl acetate, shake well to extract, evaporate the extract on a water bath, add 1ml of methanol to the residue to dissolve it as the test solution; take another 0.5g of Danshen control medicinal material, add appropriate amount of water, decoct for half an hour, filter, add water to the filtrate to 10ml, and prepare the control medicinal material solution in the same way; according to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5μl of the above-mentioned control medicinal material solution and 10μl of the test solution, respectively, and spot them on the same silica gel G thin layer plate, use chloroform-acetone-formic acid (25:10:4) as the developing agent, develop, take out, dry, fumigate with concentrated ammonia solution for 3 minutes, and inspect under ultraviolet light (365nm); It is identified by the following method: in the chromatogram of the test sample, a fluorescent spot of the same color appears at the corresponding position of the reference sample. Take 50 ml of this product, steam it in a water bath until it is almost dry, add 50 ml of 45% ethanol solution containing 7% sulfuric acid to dissolve the residue, reflux in a water bath for 1 hour, cool, extract twice with petroleum ether (30-60°C), 50 ml each time, combine the extracts, add 30 ml of water to wash, evaporate the petroleum ether solution, and dissolve the residue in 1 ml of methanol as the test solution; take another ginsengdiol reference substance, add methanol to make a solution containing 1 mg per 1 ml, as the reference substance solution; according to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5 μl of the above test substance and reference substance solutions, respectively, and spot them on the same silica gel G plate, use chloroform-ether (1:1) as the developing solvent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, heat at 105°C until the spots are clearly colored, and inspect under ultraviolet light (365nm); The relative density is 1.01-1.10 as measured by the method described in 0601 of the General Rules of Part IV of the 2020 edition of the Chinese Pharmacopoeia; and / or The pH value is determined according to the method recorded in General Chapter 0631 of Part IV of the 2020 edition of the Chinese Pharmacopoeia, and is within the range of 3.0 to 4.

5.

8. The Danlan Tongluo oral liquid according to claim 1, wherein the content of protocatechuic aldehyde is determined by the following HPLC method, and each 1 ml contains more than 20 μg of protocatechuic aldehyde: Determined by high performance liquid chromatography according to the general rule 0512 of Part IV of the 2020 edition of the Chinese Pharmacopoeia; Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as filler, methanol-0.04% glacial acetic acid (16:84) was used as mobile phase, and the detection wavelength was 280nm; the theoretical plate number calculated based on the protocatechuic aldehyde peak should be no less than 2500; Preparation of reference solution: accurately weigh 10 mg of protocatechuic aldehyde reference substance, place it in a 50 ml volumetric flask, dissolve it with methanol and dilute it to the mark, shake well; accurately pipette 1 ml, place it in a 10 ml volumetric flask, add methanol to dilute it to the mark, shake well, and the solution is ready; Preparation of test solution: accurately pipette 2.0 ml of Danlan Tongluo oral solution into a 10 ml volumetric flask, add methanol to the mark, shake thoroughly, let stand for 30 minutes, pipette the above clear solution, filter with a microporous filter membrane (0.45 μm), discard the initial filtrate, and take the subsequent filtrate to obtain; Determination method: Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

9. A method for preparing the Danlan Tongluo oral liquid according to any one of claims 1 to 8, the preparation of each 1000 ml of the Danlan Tongluo oral liquid comprising the following steps: (1) 150 g of Danshen was decocted with water three times, decocted for 2-2.5 hours with 6-8 times the amount of water for the first time, decocted for 1.5-2 hours with 6 times the amount of water for the second time, and decocted for 1.5 hours with 4-5 times the amount of water for the third time, the decoctions were combined, filtered, and the filtrate was concentrated to a concentrated solution with a relative density of 1.27-1.35 (40-50° C.); (2a) Take 1 g of total saponins of Gynostemma pentaphyllum, dissolve it in water and set aside; take another 120 g of sucrose to make syrup, combine it with the above concentrate, total saponins of Gynostemma pentaphyllum and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill and sterilize (115°C, 20min), and obtain the sugar-containing Danlan Tongluo oral solution; or, (2b) Take 1 g of total saponins of Gynostemma pentaphyllum and 300 mg of stevioside, dissolve them in water, combine them with the above-mentioned concentrate and kiwi fruit juice, add water to nearly the full amount, adjust the pH of the solution to 3.5-4.0 with 2M hydrochloric acid solution or 2M sodium hydroxide solution, add water to 1000 ml, mix well, filter (0.45µm microporous filter membrane), fill, and sterilize (115°C, 20min) to obtain a sugar-free Danlan Tongluo oral liquid; for example, 1-10 g, for example 2.5-6 g, of calcium lactate is added to the total saponins of Gynostemma pentaphyllum.

10. Use of the Danlan Tongluo oral liquid according to any one of claims 1 to 8 in the preparation of a medicine having the effects of removing blood stasis, unblocking meridians, invigorating qi and regulating the middle, or in the preparation of a medicine for improving palpitations, chest tightness, fatigue, shortness of breath, insomnia and loss of appetite caused by deficiency of both qi and blood.

Images