Concentration method for improving hesperidin transfer rate in alcohol precipitation process

Abstract

The invention discloses a concentration method for improving the hesperidin transfer rate in the alcohol precipitation process, and belongs to the technical field of traditional Chinese medicine extraction. The method comprises the following steps: (1) concentrating an extracting solution containing hesperidin through MVR (Mechanical Vapor Recompression) to obtain clear paste; and (2) mixing the clear paste obtained in the step (1) with ethanol to obtain a mixture. According to the method, the hesperidin transfer rate in the alcohol precipitation process is remarkably increased by using an MVR concentration mode and combining specific alcohol precipitation process parameters, the process is simple and easy to operate, and the hesperidin transfer rate in the alcohol precipitation process can be increased to 50% or above.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine extraction, and particularly relates to a concentration method for improving the hesperidin transfer rate in an alcohol precipitation process. Background Art

[0002] Hesperidin is also known as dihydroflavonoid glycoside, with a molecular formula of C 28 H 34 O 15 , density is 1.65g / cm 3 It is an off-white or light yellow crystalline powder, odorless and tasteless. It is easily soluble in pyridine or dimethylformamide, and insoluble in ethanol or water. Hesperidin is mainly found in citrus fruits, especially in the peels of tangerines, oranges, sweet oranges and lemons. It has the effects of enhancing capillary toughness, reducing capillary fragility, protecting capillaries, shortening bleeding time, maintaining osmotic pressure, lowering cholesterol, and preventing microvascular rupture and bleeding.

[0003] Chinese patent CN118005703A discloses a method for recovering hesperidin and rutin from hesperidin crystallization mother liquor, comprising: step S1: membrane filtration: the hesperidin crystallization mother liquor is then filtered by ceramic membrane and nanofiltration membrane in sequence; step S2: chromatographic separation: the nanofiltration membrane filtrate is subjected to chromatographic separation, 50-95% methanol aqueous solution is used as a gradient elution solvent, and the 1st 2BV eluate and the 3rd 4BV eluate are collected respectively; step S3: rutin crystallization: the 1st 2BV eluate is concentrated to a certain solid content, a crystallization solvent is added for cooling and crystallization, and the product rutin is obtained; step S4: hesperidin crystallization: the 3rd 4BV eluate is concentrated to a certain solid content, a crystallization solvent is added for cooling and crystallization, and the product hesperidin is obtained. This method uses multiple membrane treatments and requires chromatographic separation at the same time. The steps are relatively cumbersome and difficult to mass produce.

[0004] Chinese patent CN117783363A discloses a fingerprint of Juanxiao tablets and a method for establishing the same, comprising: using isorientin, isovitexin, naringin, hesperidin, melissa officinalis, aloe-emodin, nobiletin and tangeretin as reference substances, and Juanxiao tablets as test substances; using HPLC to detect the reference substances and the test substances, and then performing comparative analysis to determine the common characteristic peaks of the Juanxiao tablets. The method for forming the Quxiao tablet is as follows: ginger is squeezed to form ginger juice; rhubarb is crushed to form rhubarb powder; the remaining raw materials are distilled by water vapor and the distillate is collected; the distilled water is filtered to form a first filtrate; the residue after distillation is water-extracted and then filtered to form a second filtrate; the first filtrate and the second filtrate are mixed and then mixed with an alcohol solvent and allowed to stand, and then filtered to form a third filtrate, and the third filtrate is concentrated to form an extract powder; the extract powder and rhubarb powder are mixed and crushed, and then a filler and a wetting agent are added to granulate and dry; then ginger juice and the distillate are added to mix evenly, and then a filler is added to compress the tablet.

[0005] However, in the preparation process of this patent, an alcohol precipitation process is adopted. Since hesperidin is slightly soluble in hot water but insoluble in ethanol, the transfer rate of hesperidin decreases significantly during the alcohol precipitation process, which often leads to problems such as unqualified hesperidin content or reduced biological effect of the product.

[0006] At present, there is still a lack of a simple and effective concentration method to improve the hesperidin transfer rate during alcohol precipitation. Summary of the invention

[0007] In view of this, the purpose of the present invention is to provide a simple and effective concentration method for improving the hesperidin transfer rate during alcohol precipitation. The present invention studies the concentration method, alcohol precipitation process parameters, etc., and finds that different concentration methods have obvious effects on improving the hesperidin transfer rate during alcohol precipitation. It is unexpectedly found that when the MVR concentration method is used, the hesperidin transfer rate during alcohol precipitation can be significantly improved.

[0008] Terminology explanation: In the present invention, "MVR concentration" refers to concentration through an MVR concentration device. MVR concentration device is the abbreviation of mechanical vapor recompression. It is a new type of evaporator that uses evaporation to compress the secondary steam generated by the evaporator and reuse it. The core of the MVR concentration device lies in its unique vapor recompression technology. The evaporator in the device heats the wastewater to a boiling state to generate secondary steam. The steam is then introduced into the compressor, where its temperature and pressure are increased through compression, and then returned to the evaporator as a heat source to continue heating the wastewater. Such a cycle process not only realizes the evaporation and concentration of wastewater, but also makes full use of the latent heat of steam and improves energy efficiency.

[0009] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0010] In one aspect, the present invention provides a concentration method for improving the hesperidin transfer rate during alcohol precipitation, comprising the following steps:

[0011] (1) Concentrating the hesperidin-containing extract by MVR to obtain a clear paste;

[0012] (2) Mixing the clear paste obtained in step (1) with ethanol to obtain a mixture.

[0013] Preferably, in step (1), the MVR concentration conditions are: vacuum degree 0.01-0.03 MPa, temperature 85-95° C., and relative density of the clear paste is 1.08-1.15.

[0014] Preferably, in step (2), the ethanol concentration in the mixture is 60-80%, more preferably 65-70%, and most preferably 70%.

[0015] Preferably, in step (2), the mixture is further subjected to the steps of standing and filtering.

[0016] Further preferably, the standing temperature is 20-45°C, and the time is 12-48h; as a further preferred example of the present invention, the standing temperature is 25-30°C, and the time is 24h.

[0017] As a specific example of the present invention, in step (1), the hesperidin-containing extract is prepared by the following steps:

[0018] Tangerine peel, green peel, vitex negundo, areca nut and scutellaria baicalensis seed are distilled with steam, and the distillate is collected; the aqueous solution after distillation is filtered to obtain filtrate 1; the residue is decocted again with water to obtain filtrate 2; filtrate 1 and filtrate 2 are combined to obtain an extract containing hesperidin.

[0019] Preferably, the steam distillation conditions are: adding 8-10 times of water and distilling for 1-3 hours.

[0020] Preferably, the conditions for decocting with water are: adding 6-8 times of water and decocting for 1-3 hours.

[0021] In another aspect, the present invention provides application of the above concentration method in preparing a pharmaceutical preparation.

[0022] Preferably, the preparation is any one of tablets, granules, pills, powders, granules, effervescent tablets and capsules. As a specific example of the present invention, the preparation is a tablet.

[0023] Finally, the present invention provides a pharmaceutical preparation, which is prepared according to the following steps:

[0024] (1) Squeeze ginger to obtain ginger juice; crush rhubarb into fine rhubarb powder;

[0025] (2) Distilling dried orange peel, green peel, vitex negundo, areca nut, and scutellaria baicalensis seed with steam to obtain a distillate; filtering the aqueous solution after distillation to obtain a filtrate 1; boiling the residue with water again to obtain a filtrate 2; combining the filtrate 1 and the filtrate 2 to obtain an extract containing hesperidin;

[0026] (3) Concentrating the hesperidin-containing extract obtained in step (2) by MVR to obtain a clear paste;

[0027] (4) mixing the clear paste obtained in step (3) with ethanol to obtain a mixture, wherein the ethanol concentration in the mixture is 60-80%;

[0028] (5) The mixture obtained in step (4) is allowed to stand, filtered, and concentrated to obtain a thick paste, to which rhubarb powder is added, dried, crushed, ginger juice and distillate are added, and granulated.

[0029] Preferably, in step (1), the mesh size of the rhubarb powder is 80-100 mesh.

[0030] Preferably, in step (2), the conditions for the steam distillation are: adding 8-10 times of water and distilling for 1-3 hours.

[0031] Preferably, in step (2), the conditions for boiling with water are: boiling with 6-8 times the water for 1-3 hours. Preferably, in step (3), the conditions for MVR concentration are: vacuum degree 0.01-0.03MPa, temperature 85-95°C, and the MVR concentration is concentrated to a relative density of 1.08-1.15.

[0032] Preferably, in step (4), the ethanol concentration in the mixture is 60-80%, more preferably 65-70%, and most preferably 65%.

[0033] Preferably, in step (5), the temperature of the standing still is 20-40°C and the time is 12-48 hours; more preferably, the temperature of the standing still is 25°C and the time is 24 hours. As a specific example of the present invention, the temperature of the standing still is 25°C and the time is 24 hours.

[0034] Preferably, in step (5), the density of the thick paste is 1.25-1.30.

[0035] In step (5), the granulation is prepared into a corresponding pharmaceutical dosage form using existing technical means in the art.

[0036] As a specific example of the present invention, in the preparation method, the raw material formula includes, by weight: 300-500 parts of scutellaria baicalensis seeds, 300-500 parts of green peel, 300-500 parts of tangerine peel, 500-700 parts of nivalis nigrum seeds, 300-500 parts of areca nut, 100-200 parts of rhubarb and 50-100 parts of ginger.

[0037] The beneficial effects of the present invention are:

[0038] The invention uses MVR concentration in combination with specific alcohol precipitation process parameters to significantly improve the hesperidin transfer rate in the alcohol precipitation process. The process is simple and easy to operate. The method can improve the hesperidin transfer rate in the alcohol precipitation process to more than 50%. DETAILED DESCRIPTION

[0039] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present application.

[0040] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0041] The raw material formula is as follows:

[0042] 300-500g of scutellaria baicalensis seeds, 300-500g of green tangerine peel, 300-500g of dried tangerine peel, 500-700g of nivalis seeds, 300-500g of betel nut, 100-200g of rhubarb, and 50-100g of ginger.

[0043] As a specific embodiment of the present invention, the formula is as follows:

[0044] 448g of scutellaria baicalensis seeds, 448g of green tangerine peel, 448g of dried tangerine peel, 625g of nigrum seed, 448g of betel nut, 125g of rhubarb, and 100g of ginger.

[0045] Example 1

[0046] (1) Measure the raw materials according to the formula, squeeze the ginger to obtain ginger juice; crush the rhubarb into fine powder;

[0047] (2) Tangerine peel, green peel, Vitex negundo, Areca catechu, and Lepidium tiliaceum were wrapped with cotton cloth and distilled with steam under the condition of adding 8 times water and distilling for 2 hours, collecting the distillate; filtering the aqueous solution after distillation to obtain filtrate 1; adding water to the residue and decocting it once again under the condition of 6 times water and decocting it for 2 hours, filtering it, and combining it with filtrate 1 and filtrate 2 to obtain an extract containing hesperidin;

[0048] (3) The hesperidin-containing extract was concentrated to a clear paste with a relative density of 1.08-1.15 (80° C.) by MVR. The conditions for MVR concentration were: vacuum degree 0.2 MPa, temperature 90° C.;

[0049] (4) adding ethanol to the clear paste to make the ethanol concentration 65%, standing at 25° C. for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to a thick paste with a relative density of 1.25-1.30 (80° C.);

[0050] (5) Add rhubarb powder to the thick paste, dry it, crush it into fine powder, spray it with ginger juice and distillate, and granulate and tablet it according to conventional technology.

[0051] Example 2

[0052] The difference from Example 1 is that in step (4), the standing temperature is 45° C., and the rest is the same.

[0053] Example 3

[0054] The difference from Example 1 is that in step (4), the standing temperature is 30° C., and the rest is the same.

[0055] Example 4

[0056] The difference from Example 1 is that in step (4), the ethanol concentration is 60%, and the rest are the same.

[0057] Example 5

[0058] The difference from Example 1 is that in step (4), the ethanol concentration is 70%, and the rest are the same.

[0059] Comparative Example 1

[0060] The difference from Example 1 is that in step (3), MVR concentration is replaced by atmospheric pressure direct fire concentration, specifically heating to boiling in an induction cooker, and the rest is the same.

[0061] Comparative Example 2

[0062] The difference from Example 1 is that in step (3), MVR concentration is replaced by atmospheric pressure direct fire concentration, specifically heating to boiling in an induction cooker, and in step (4), the standing temperature is 45° C., and the rest are the same.

[0063] Comparative Example 3

[0064] The difference from Example 1 is that in step (3), MVR concentration is replaced by atmospheric pressure direct fire concentration, and the condition is heating to boiling in an induction cooker. In step (4), the standing temperature is 30° C., and the rest is the same.

[0065] Comparative Example 4

[0066] The difference from Example 1 is that in step (3), MVR concentration is replaced by atmospheric pressure direct fire concentration, specifically heating to boiling in an induction cooker, and in step (4), the ethanol concentration is 60%, and the rest are the same.

[0067] Comparative Example 5

[0068] The difference from Example 1 is that in step (3), MVR concentration is replaced by atmospheric pressure direct fire concentration, specifically heating to boiling in an induction cooker, and in step (4), the ethanol concentration is 70%, and the rest are the same.

[0069] Comparative Example 6

[0070] The difference from Example 1 is that in step (3), MVR concentration is replaced by vacuum double-effect concentration under the following conditions: vacuum degree 0.7-0.8 MPa, temperature 70-80°C, and the rest are the same.

[0071] Comparative Example 7

[0072] The difference from Example 1 is that in step (3), MVR concentration is replaced by vacuum double-effect concentration under the following conditions: vacuum degree 0.7-0.8 MPa, temperature 70-80°C, in step (4), the standing temperature is 45°C, and the rest are the same.

[0073] Comparative Example 8

[0074] The difference from Example 1 is that in step (3), MVR concentration is replaced by vacuum double-effect concentration under the following conditions: vacuum degree 0.7-0.8 MPa, temperature 70-80°C, in step (4), the standing temperature is 30°C, and the rest are the same.

[0075] Comparative Example 9

[0076] The difference from Example 1 is that in step (3), MVR concentration is replaced by vacuum double-effect concentration under the following conditions: vacuum degree 0.7-0.8 MPa, temperature 70-80° C., in step (4), ethanol concentration is 60%, and the rest are the same.

[0077] Comparative Example 10

[0078] The difference from Example 1 is that in step (3), MVR concentration is replaced by vacuum double-effect concentration under the following conditions: vacuum degree 0.7-0.8 MPa, temperature 70-80°C, in step (4), ethanol concentration is 70%, and the rest are the same.

[0079] Results

[0080] The transfer rate of hesperidin was detected for Examples 1-6 and Comparative Examples 1-8 by the following method:

[0081] (1) Chromatographic conditions

[0082] 1) Chromatographic column: Agilent SB C18, 5μm, 4.6*250nm

[0083] 2) Mobile phase: methanol-glacial acetic acid-water (30:1:70)

[0084] 3) Column temperature: 35°C

[0085] 4) Flow rate: 1mL / min

[0086] 5) Detection wavelength: 285nm

[0087] (2) Preparation of reference solution

[0088] Take an appropriate amount of hesperidin reference substance, weigh it accurately, and add methanol to make a solution containing 30 μg per 1 mL.

[0089] (3) Preparation of test solution

[0090] Take 0.3 g of the extract, weigh it accurately, put it in a 100 mL volumetric flask, add 10 mL of water to dilute, shake well, add 80 mL of methanol, ultrasonic (99%, power 40 kHz) for 40 minutes, take it out, cool, add methanol to the scale, shake well, filter, and take the filtrate.

[0091] (4) Determination method

[0092] Accurately pipette 5 μL of reference solution and test solution respectively, inject into liquid chromatograph, and measure to obtain the result.

[0093] The results are as follows:

[0094]

[0095]

[0096] The experimental results show that the hesperidin transfer rate can be increased to more than 55% by using the MVR concentration method in Examples 1-5. At the same time, both the static conditions and the ethanol concentration will affect the hesperidin transfer rate. Under the comprehensive conditions of Example 5, the hesperidin transfer rate can reach 60-62%, which is the best example. The results of Comparative Examples 1-10 show that the hesperidin transfer rate is significantly reduced by using the induction cooker heating to boiling or the decompression dual-effect concentration method, indicating that the MVR concentration of the extract can significantly improve the hesperidin transfer rate of the extract during the alcohol precipitation process.

Claims

1. A concentration method for improving the hesperidin transfer rate during alcohol precipitation, characterized in that: The following steps are involved: (1) Concentrating the hesperidin-containing extract by MVR to obtain a clear paste; (2) Mixing the clear paste obtained in step (1) with ethanol to obtain a mixture.

2. The concentration method according to claim 1, characterized in that In step (1), the MVR concentration conditions are: vacuum degree 0.01-0.03 MPa, temperature 85-95° C., and the relative density of the clear paste is 1.08-1.

15.

3. The concentration method according to claim 1, characterized in that: In step (2), the concentration of ethanol in the mixture is 60-80%, preferably 65-70%, and most preferably 70%.

4. The concentration method according to claim 1, characterized in that: In step (2), the mixture is further subjected to the steps of standing and filtering; preferably, the standing temperature is 20-45°C and the time is 12-48h, and more preferably, the standing temperature is 25-30°C and the time is 24h.

5. Use of the concentration method according to any one of claims 1 to 4 in the preparation of pharmaceutical preparations.

6. A pharmaceutical preparation, characterized in that Prepare according to the following steps: (1) Squeeze ginger to obtain ginger juice; crush rhubarb into fine rhubarb powder; (2) Distilling dried orange peel, green peel, vitex negundo, areca nut, and scutellaria baicalensis seed with steam to obtain a distillate; filtering the aqueous solution after distillation to obtain a filtrate 1; boiling the residue with water again to obtain a filtrate 2; combining the filtrate 1 and the filtrate 2 to obtain an extract containing hesperidin; (3) Concentrating the hesperidin-containing extract obtained in step (2) by MVR to obtain a clear paste; (4) mixing the clear paste obtained in step (3) with ethanol to obtain a mixture; (5) The mixture obtained in step (4) is allowed to stand, filtered, and concentrated to obtain a thick paste, to which rhubarb powder is added, dried, crushed, ginger juice and distillate are added, and granulated.

7. The preparation according to claim 6, characterized in that In step (2), the conditions for steam distillation are: adding 8-10 times of water and distilling for 1-3 hours; the conditions for decoction with water are: adding 6-8 times of water and decoct for 1-3 hours.

8. The preparation according to claim 6, characterized in that In step (3), the MVR concentration conditions are: vacuum degree 0.01-0.03 MPa, temperature 85-95° C., and the MVR is concentrated to a relative density of 1.08-1.

15.

9. The preparation according to claim 6, characterized in that In step (4), the concentration of ethanol in the mixture is 60-80%, preferably 65-70%.

10. The preparation according to claim 6, characterized in that In step (5), the standing temperature is 20-40° C., the standing time is 12-48 hours, and the density of the thick paste is 1.25-1.30.

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