Pulse-activating decoction and preparation method thereof

Abstract

The invention discloses a pulse-activating decoction and a preparation method thereof. The invention aims to solve the problem of loss of part of fat-soluble active ingredients caused by solution polarity change in a percolate concentration working section in a pulse-activating decoction production process in pharmacopeia and the problem that carbohydrates are introduced into auxiliary materials in order to improve the mouth feel, so that the pulse-activating decoction is not suitable for patients with glucose metabolism disorders. The invention particularly relates to a production process of a pulse-activating decoction with hydroxypropyl cyclodextrin-assisted leaching and momordica grosvenori sugar substitute. According to the invention, the hydrophobic property of the inner cavity of the hydroxypropyl cyclodextrin is utilized to solubilize and stabilize fat-soluble components in a water-phase solution, so that the problem of loss of effective fat-soluble components is solved, and the problem of medication of sugar-avoiding patients such as diabetics and the like is solved by utilizing the momordica grosvenori leaching solution to replace sugar. The pulse-activating decoction prepared by the invention can effectively meet the requirements of product characters that the product is red brown clarified liquid, fragrant in smell, sour and sweet in taste and slightly bitter.

Description

Technical Field

[0001] The invention belongs to the technical field of medicine manufacturing, and specifically relates to a Shengmai drink and a preparation method thereof. Background Art

[0002] The prescription of Shengmaiyin given in the 2020 edition of the Chinese Pharmacopoeia is 100g of red ginseng, 200g of Ophiopogon japonicus and 100g of Schisandra chinensis; its production process is to first crush red ginseng, Ophiopogon japonicus and Schisandra chinensis into coarse powder, then use 65% ethanol as a solvent, soak for 24 hours and then percolate, collect about 4500ml of percolate, concentrate under reduced pressure to about 250ml, cool, dilute with 400ml of water, filter, add 300ml of 60% syrup and appropriate amount of preservatives, and adjust the pH value to the specified range, add water to 1000ml, stir well, let stand, filter, fill, sterilize, and obtain a yellow-brown to reddish-brown clear liquid product; the product has a fragrant smell, sweet and sour taste, and slightly bitter. However, the color of Shengmaiyin produced strictly in accordance with the preparation method of the Chinese Pharmacopoeia is not very clear, and there will be more turbidity after long-term storage. Since the raw materials in Shengmaiyin are percolated to extract a large amount of fat-soluble components in the medicinal materials, 400ml of water is added to dilute the extract after ethanol is recovered. The oil-soluble active ingredients precipitate out of the solution and are lost when the ethanol is evaporated. Then, in the preparation process, when the pH value is adjusted and water is added to 1000 ml, the polarity of the solution increases again, causing some oil-soluble ingredients to form amorphous precipitation, which will disperse with a slight shake and cannot be effectively removed, resulting in the product's color not being very clear and becoming more turbid after long-term storage.

[0003] In view of the above problems, patent CN 116271059 A proposed a method of adding polysorbate 80 surfactant to Shengmai Drink to solubilize fat-soluble components, which played a role in clarifying the product to a certain extent. However, surfactant emulsification solubilization technology is a thermodynamically unstable system after all, and cannot solve the problem of turbidity after long-term storage. Water-soluble hydroxypropyl cyclodextrin has a good hydrophobic cavity in the molecule, which is conducive to the solubilization and stabilization of the aqueous solution of fat-soluble substances. Summary of the invention

[0004] The purpose of the present invention is to overcome the defects of the prior art and provide a Shengmai Yin solution and a preparation method thereof.

[0005] In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a Shengmai Yin solution, which includes a concentrate of Codonopsis pilosula, Ophiopogon japonicus and Schisandra chinensis as main ingredients, and the main ingredient concentrate is prepared by using ethanol as solvent and hydroxypropyl cyclodextrin as auxiliary leaching agent for diafiltration.

[0006] Furthermore, the hydroxypropyl cyclodextrin is 2-hydroxypropyl-α-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin or 2-hydroxypropyl-γ-cyclodextrin.

[0007] Furthermore, the weight proportions of the components in the main material are: 80-100 parts of Codonopsis pilosula, 160-200 parts of Ophiopogon japonicus, and 80-100 parts of Schisandra chinensis.

[0008] Furthermore, the amount of hydroxypropyl cyclodextrin used accounts for 5% to 10% of the total weight of the main material.

[0009] Furthermore, the Shengmai Drink solution also contains Luo Han Guo extract and sodium benzoate.

[0010] Furthermore, monk fruit accounts for 5% to 10% of the total weight of the main ingredients; sodium benzoate accounts for 1.6% to 2.5% of the total weight of the main ingredients.

[0011] A method for preparing the above-mentioned Shengmaiyin solution comprises the following steps:

[0012] (1) Add Codonopsis pilosula, Ophiopogon japonicus and Schisandra chinensis into a grinder and grind into coarse powder;

[0013] (2) using ethanol as a solvent and hydroxypropyl cyclodextrin as an auxiliary leaching agent, soaking the crude powder in an alcohol-water solution containing hydroxypropyl cyclodextrin;

[0014] (3) After the soaking is completed, a percolation operation is performed to collect the percolation liquid; the collected percolation liquid is concentrated under reduced pressure;

[0015] (4) Adjust the pH value of the concentrate; add water and filter, can and sterilize to obtain Shengmai Yin solution.

[0016] Furthermore, the concentration of ethanol in step (2) is 30% to 60%.

[0017] Furthermore, the coarse powder in step (2) is immersed in the alcohol aqueous solution containing hydroxypropyl cyclodextrin for 24 to 36 hours.

[0018] Furthermore, the pH value of the concentrated solution in step (4) is adjusted to be within the range of 4.5 to 7.0.

[0019] The present invention utilizes water-soluble hydroxypropyl cyclodextrin, which has a good hydrophobic cavity in the molecule and is beneficial to the solubilization and stabilization of the aqueous solution of the fat-soluble substance.

[0020] Since the Chinese Pharmacopoeia clearly proposes to add 300ml of 60% syrup to improve the taste of Shengmai Drink, this is not conducive to the needs of patients who avoid sugar. In order to meet the needs of patients who avoid sugar such as diabetes, obesity, hyperlipidemia, coronary heart disease, etc., patents CN117797090A and CN 110384756 A, etc., propose different sugar-replacing processes such as stevioside and sucralose, but they are only sugar-replacing effects. The water extract of Momordica grosvenori is sweet and has obvious antitussive and expectorant effects, has the effect of reducing the activity of serum alanine aminotransferase, can significantly increase the percentage of acid naphthyl acetate esterase-positive lymphocytes in the peripheral blood of experimental animals, and can enhance the body's cellular immune function. The present invention uses the sweet taste of Momordica grosvenori water extract, which has obvious antitussive and expectorant effects, to add it to Shengmai Drink to achieve sugar-replacing and synergistic functions.

[0021] The advantages and beneficial effects of the present invention are as follows: the present invention uses water-soluble hydroxypropyl cyclodextrin as an auxiliary leaching additive to propose a new auxiliary leaching process. The addition of hydroxypropyl cyclodextrin in the process effectively reduces the amount of ethanol used, and can utilize the hydrophobic cavity of the water-soluble hydroxypropyl cyclodextrin to effectively solubilize the extraction and stabilization of the fat-soluble effective components in Shengmai Drink, and completely solve the problem of long-term turbidity. The addition of Momordica grosvenori solves the problem of drug safety for diabetics, and also introduces the antitussive and expectorant effects of Momordica grosvenori to play a sugar substitute and synergistic function. The present invention has simple production conditions, high efficiency, and good feasibility of implementation. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the process flow chart for the preparation method of Shengmai Drink in the 2020 edition of the "Chinese Pharmacopoeia".

[0023] Figure 2 The present invention is a process flow chart of a method for preparing Shengmai Drink according to an embodiment of the present invention. DETAILED DESCRIPTION

[0024] In order to enable those skilled in the art to better understand the solution of the present application, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present application.

[0025] It should be noted that the terms "including" and "having" and any variations thereof in the specification and claims of the present application and the above-mentioned drawings are intended to cover non-exclusive inclusions. For example, a process, method, system, product or apparatus comprising a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or apparatuses.

[0026] Example 1

[0027] The process of this embodiment is as follows Figure 2 As shown, specifically, 80g of Codonopsis pilosula, 160g of Ophiopogon japonicus, and 80g of Schisandra chinensis were added to a grinder and crushed into coarse powder; 1000g of 30% ethanol was used as a solvent, 16g 2-Hydroxypropyl-α-cyclodextrin is used as an auxiliary leaching agent. The crushed herbs are soaked in ethanol containing 2-hydroxypropyl-α-cyclodextrin. After soaking at room temperature for 24 hours, a percolation operation is performed to collect the percolation liquid. The collected percolation liquid is concentrated under reduced pressure to recover ethanol, and its volume is reduced to about 250 ml. After cooling, a concentrated solution (C1) is obtained. 16 g of crushed monk fruit is added to 400 ml of water and leached at 80° C. for 30 minutes, and then the volume is reduced to about 200 ml. The filtrate is cooled to room temperature and filtered to obtain a filtrate. The monk fruit extract is added to the above-mentioned concentrated solution (C1), and then 300 ml of water and 5 g of sodium benzoate are added to the concentrated solution. The pH value of the liquid is adjusted to 4.5 to 7.0 with sodium carbonate. Finally, an appropriate amount of water is added to the solution to make the total volume reach 1000 ml, and then the solution is stirred, allowed to stand and filtered. The filtered solution is filled and sterilized to obtain the final product.

[0028] It should be noted that cyclodextrin is included in the 2020 edition of the Chinese Pharmacopoeia as a pharmaceutical excipient. Therefore, cyclodextrin is a commonly used excipient for pharmaceuticals.

[0029] According to the Technical Guidelines for Research on Pharmaceutical Changes of Marketed Traditional Chinese Medicines (Trial Implementation), Item 5 "Changes to excipients in the formulation", Paragraph 1 "Minor changes", and Article 3 "Delete flavors, pigments, and flavoring agents, or reduce the dosage; increase or change the type or dosage of flavors, pigments, and flavoring agents (except for children's medicines)". Shengmai Yin does not involve children's medicines, so it is feasible to add "add an appropriate amount of monk fruit extract".

[0030] Example 2

[0031] The process of this embodiment is as follows Figure 2As shown, specifically, 100g of Codonopsis pilosula, 200g of Ophiopogon japonicus, and 100g of Schisandra chinensis were added to a grinder and crushed into coarse powder; 1000g of 50% ethanol was used as a solvent, 40g 2-Hydroxypropyl-α-cyclodextrin is used as an auxiliary leaching agent. The crushed herbs are soaked in ethanol containing 2-hydroxypropyl-α-cyclodextrin. After soaking at room temperature for 36 hours, a percolation operation is performed to collect the percolation liquid. The collected percolation liquid is concentrated under reduced pressure to recover ethanol, and its volume is reduced to about 250 ml. After cooling, a concentrated solution (C1) is obtained. 40 g of crushed monk fruit is added to 1000 ml of water and leached at 100° C. for 30 minutes, and then the volume is reduced to about 200 ml. The filtrate is cooled to room temperature and filtered to obtain a filtrate. The monk fruit extract is added to the above-mentioned concentrated solution (C1), and then 300 ml of water and 5 g of sodium benzoate are added to the concentrated solution. The pH value of the liquid is adjusted to 4.5 to 7.0 with sodium carbonate. Finally, an appropriate amount of water is added to the solution to make the total volume reach 1000 ml, and then the solution is stirred, allowed to stand and filtered. The filtered solution is filled and sterilized to obtain the final product.

[0032] Example 3

[0033] The process of this embodiment is as follows Figure 2 As shown, specifically, 100g of Codonopsis pilosula, 200g of Ophiopogon japonicus, and 100g of Schisandra chinensis were added to a grinder and crushed into coarse powder; 1000g of 50% ethanol was used as a solvent, 40g 2-Hydroxypropyl-β-cyclodextrin is used as an auxiliary leaching agent. The crushed herbs are soaked in ethanol containing 2-hydroxypropyl-β-cyclodextrin. After soaking at room temperature for 30 hours, a percolation operation is performed to collect the percolation liquid. The collected percolation liquid is concentrated under reduced pressure to recover ethanol, and its volume is reduced to about 250 ml. After cooling, a concentrated solution (C1) is obtained. 40 g of crushed Momordica grosvenori is added to 1000 ml of water and leached at 90° C. for 30 minutes, and then the volume is reduced to about 200 ml. The filtrate is cooled to room temperature and filtered to obtain a filtrate. The Momordica grosvenori extract is added to the above-mentioned concentrated solution (C1), and then 300 ml of water and 10 g of sodium benzoate are added to the concentrated solution. The pH value of the liquid is adjusted to 4.5 to 7.0 with sodium carbonate. Finally, an appropriate amount of water is added to the solution to make the total volume reach 1000 ml, and then the solution is stirred, allowed to stand and filtered. The filtered solution is filled and sterilized to obtain the final product.

[0034] Example 4

[0035] The process of this embodiment is as follows Figure 2Specifically, 100 g of Codonopsis pilosula, 200 g of Radix Ophiopogonis, and 100 g of Schisandrae Chinensis were added to a grinder and crushed into coarse powder; 1000 g of 60% ethanol was used as a solvent, 40 g 2-Hydroxypropyl-γ-cyclodextrin is used as an auxiliary leaching agent. The crushed herbs are soaked in ethanol containing 2-hydroxypropyl-γ-cyclodextrin. After soaking at room temperature for 30 hours, a percolation operation is performed to collect the percolation liquid. The collected percolation liquid is concentrated under reduced pressure to recover ethanol, and its volume is reduced to about 250 ml. After cooling, a concentrated solution (C1) is obtained. 40 g of crushed Momordica grosvenori is added to 1000 ml of water and leached at 80° C. for 30 minutes, and then concentrated under reduced pressure to reduce its volume to about 200 ml. The filtrate is cooled to room temperature and filtered to obtain a filtrate. The Momordica grosvenori extract is added to the above-mentioned concentrated solution (C1), and then 300 ml of water and 10 g of sodium benzoate are added to the concentrated solution. The pH value of the liquid is adjusted to 4.5 to 7.0 with sodium carbonate. Finally, an appropriate amount of water is added to the solution to make the total volume reach 1000 ml, and then the solution is stirred, allowed to stand and filtered. The filtered solution is filled and sterilized to obtain the final product.

[0036] Example 5

[0037] The process of this embodiment is as follows Figure 2 As shown, specifically, 90g of Codonopsis pilosula, 180g of Ophiopogon japonicus, and 90g of Schisandra chinensis were added to a grinder and crushed into coarse powder; 1000g of 50% ethanol was used as a solvent, 18g 2-Hydroxypropyl-γ-cyclodextrin is used as an auxiliary leaching agent. The crushed herbs are soaked in ethanol containing 2-hydroxypropyl-γ-cyclodextrin. After soaking at room temperature for 24 hours, a percolation operation is performed to collect the percolation liquid. The collected percolation liquid is concentrated under reduced pressure to recover ethanol, and its volume is reduced to about 250 ml. After cooling, a concentrated solution (C1) is obtained. 18 g of crushed Momordica grosvenori is added to 450 ml of water and leached at 80° C. for 30 minutes, and then a reduced pressure concentration is performed to reduce its volume to about 200 ml. The filtrate is cooled to room temperature and filtered to obtain a filtrate. The Momordica grosvenori extract is added to the above-mentioned concentrated solution (C1), and then 300 ml of water and 8 g of sodium benzoate are added to the concentrated solution. The pH value of the liquid is adjusted to 4.5 to 7.0 with sodium carbonate. Finally, an appropriate amount of water is added to the solution to make the total volume reach 1000 ml, and then the solution is stirred, allowed to stand and filtered. The filtered solution is filled and sterilized to obtain the final product.

[0038] The method of identifying Shengmai Drink is as follows:

[0039] (1) To identify the quality of the Shengmai Drink product of the present invention, 20 ml of each of the homemade Shengmai Drinks in Examples 1-5 were taken, shaken and extracted with 20 ml of n-butanol, the n-butanol solution was evaporated to dryness, 15 ml of 45% ethanol solution of sulfuric acid (7→100) was added to the residue, heated and refluxed for 1 hour, the ethanol was evaporated, and the residue was shaken and extracted with 10 ml of chloroform. The chloroform solution was separated and washed with water until neutral, dehydrated with an appropriate amount of anhydrous sodium sulfate, filtered, and the filtrate was concentrated to 1 ml as the sample to be tested. Standard ginsenodiol and ginsenotriol were added with anhydrous ethanol to prepare a mixed solution containing 1 mg per 1 ml, which was used as a reference sample. A comparison verification test was performed using thin layer chromatography (experimental conditions: sample amount 10 μl, ethyl acetate-dichloromethane (2:1) as the developing solvent, sulfuric acid methanol solution (1→2) as the color developer, heated at 105°C for about 10 minutes, and inspected under ultraviolet light (365nm)).

[0040] The results show that the samples of Examples 1-5 have substantially the same Rf values ​​as the two reference products, and the colors of the fluorescent spots are the same.

[0041] (2) Take 10 ml of each of the homemade Shengmai Drinks in Examples 1-5, add 0.5 ml of hydrochloric acid and 1 ml of water, heat and boil for 5 minutes, cool, shake and extract with 20 ml of chloroform, take the chloroform solution, concentrate to 1 ml, and use it as the test solution. Take 1 g of Radix Ophiopogonis as a control medicinal material, add 20 ml of water, decoct for 10 minutes, filter, add 0.5 ml of hydrochloric acid to the filtrate, and prepare the control medicinal material solution in the same way. According to the thin layer chromatography test, take 5 μl of each of the above two solutions, spot them on the same silica gel G thin layer plate, use dichloromethane-acetone (2:1) as the developing solvent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, and heat at 100°C until the spots are clearly colored.

[0042] (3) The results show that the samples of Examples 1-5 have substantially the same Rf values ​​as the two reference products, and the colors of the fluorescent spots are the same.

[0043] Take 10ml of each homemade Shengmai Drink in Examples 1-5, add 20ml of water, shake well, extract 3 times with ether, 30ml each time, combine the ether solution, evaporate to dryness, add 1ml of ethanol to the residue to dissolve it as the test solution. Take 1g of Schisandrae Chinensis reference medicinal material, add 20ml of chloroform, ultrasonically treat for 30 minutes, filter, evaporate the filtrate to dryness, and add 1ml of ethanol to the residue to dissolve it as the reference medicinal material solution. Take Schisandrae Chinensis Alcohol A reference substance again, add chloroform to make a solution containing 1mg per 1ml as the reference substance solution. Take 5-10μl of the samples of Examples 1-5 above, 2-5μl of the reference medicinal material solution and the reference substance solution, and spot them on the same silica gel GF thin layer plate, use the upper layer solution of petroleum ether (30-60°C)-ethyl formate-formic acid (15:5:1) as the developing agent, develop, take out, dry, and inspect under ultraviolet light (254nm).

[0044] The results show that the samples of Examples 1-5 have substantially the same Rf values ​​as the two reference products, and the colors of the fluorescent spots are the same.

[0045] (4) Relative density The relative density of Shengmai Drink of the present invention and Shengmai Drink prepared by the process of the Chinese Pharmacopoeia 2020 edition is shown in Table 1 using the fully automatic density measurement of Zhuoguang Instrument ZG-MD80. It can be seen from Table 1 that the average relative density of Shengmai Drink of the present invention is about 1.18.

[0046] Table 1

[0047]

[0048] (5) The pH value was determined according to the standard method in the prior art. (4) The pH values ​​of Shengmai Drink of the present invention and Shengmai Drink prepared by the process of the Chinese Pharmacopoeia 2020 edition are shown in Table 2.

[0049] Table 2

[0050]

[0051] (6) To evaluate the ginsenoside Rg in Shengmai Drink prepared in Examples 1-5 1 The content of schisandrae alcohol A is determined by referring to the HPLC determination method in the invention patent CN 105031207 A. Ginsenoside Rg 1 The test results of ginsenoside Rg and schisandrae alcohol A are shown in Table 3 below. 1 The content is about three times that of Shengmai Drink produced in the 2020 edition of the Chinese Pharmacopoeia, and the content of Schisandrin A is more than twice that of it. This shows that hydroxypropyl cyclodextrin-assisted extraction is beneficial to the active ingredient ginsenoside Rg 1 And the enrichment of schisandra chinensis alcohol A, which is beneficial to enhance the medicinal properties of Shengmai Drink.

[0052] Table 3

[0053]

[0054] (7) In order to judge the stability of Shengmai Drink prepared in Examples 1-5. Take 10 ml of each of the Shengmai Drink prepared in Examples 1-5 of the present invention and mix them evenly. Take 10 ml of the mixed solution and seal it. Place it under the conditions of temperature of 38-42°C and humidity of 70%-80%, and observe the stability of the first, third and sixth months. The results are shown in Table 4. It can be seen from the table that the quality of Shengmai Drink of the present invention and Shengmai Drink (i.e., sugar-containing type) produced by the process given in the 2020 edition of the Chinese Pharmacopoeia meets the requirements.

[0055] Table 4

[0056]

[0057] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Shengmai drink, characterized in that: The Shengmaiyin solution comprises concentrated solution of Codonopsis pilosula, Ophiopogon japonicus and Schisandra chinensis as main ingredients. The concentrated solution of the main ingredients is prepared by using ethanol as a solvent and hydroxypropyl cyclodextrin as an auxiliary leaching agent for diafiltration.

2. The Shengmai Drink according to claim 1, characterized in that: The hydroxypropyl cyclodextrin is 2-hydroxypropyl-α-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin or 2-hydroxypropyl-γ-cyclodextrin.

3. The Shengmai Drink according to claim 1, characterized in that: The weight proportions of the components in the main material are: 80-100 parts of Codonopsis pilosula, 160-200 parts of Ophiopogon japonicus and 80-100 parts of Schisandra chinensis.

4. The Shengmai Drink according to claim 1, characterized in that: The hydroxypropyl cyclodextrin accounts for 5% to 10% of the total weight of the main material.

5. The Shengmai Drink according to claim 1, characterized in that: The Shengmaiyin solution also contains Momordica grosvenori extract and sodium benzoate.

6. The Shengmai Drink according to claim 5, characterized in that: The monk fruit accounts for 5% to 10% of the total weight of the main material; the sodium benzoate accounts for 1.6% to 2.5% of the total weight of the main material.

7. A method for preparing the Shengmai Yin solution according to any one of claims 1 to 6, characterized in that The following steps are involved: (1) Add Codonopsis pilosula, Ophiopogon japonicus and Schisandra chinensis into a grinder and grind into coarse powder; (2) using ethanol as a solvent and hydroxypropyl cyclodextrin as an auxiliary leaching agent, soaking the crude powder in an alcohol-water solution containing hydroxypropyl cyclodextrin; (3) After the soaking is completed, a percolation operation is performed to collect the percolation liquid; the collected percolation liquid is concentrated under reduced pressure; (4) Adjust the pH value of the concentrate; add water and filter, can and sterilize to obtain Shengmai Yin solution.

8. The method for preparing the Shengmaiyin solution according to claim 7, characterized in that: The concentration of ethanol in step (2) is 30% to 60%.

9. The preparation method of Shengmai Drink according to claim 7, characterized in that: The coarse powder in step (2) is immersed in the alcohol aqueous solution containing hydroxypropyl cyclodextrin for 24 to 36 hours.

10. The preparation method of Shengmai Drink according to claim 7, characterized in that: The pH value of the concentrated solution in step (4) is adjusted to be within the range of 4.5 to 7.0.

Images