Traditional Chinese medicine composition for treating infantile pneumonia and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating infantile pneumonia and a preparation method thereof. The composition is prepared from 10-20 parts of herba ephedrae extract, 8-15 parts of semen lepidii extract, 8-15 parts of fructus perillae extract and a flavoring agent accounting for 0.5-2wt% of the composition. The preparation method comprises the steps of ephedra herb raw material pretreatment, supercritical fluid degreasing, dynamic purification, multi-stage membrane separation and purification, blending and the like. By optimizing the purification process, the retention rate of effective components can be remarkably increased, the content of impurities such as tannin can be reduced, meanwhile, the taste of the composition is improved, the medication compliance of children is improved, and the preparation method is suitable for industrial production.

Description

Technical Field

[0001] This article relates to a traditional Chinese medicine composition for treating pneumonia in children and a preparation method thereof. Background Art

[0002] Pediatric pneumonia is a common respiratory disease in pediatrics. Its main clinical features are fever, cough, shortness of breath and dyspnea, which seriously threatens children's health. In the treatment of this disease, traditional Chinese medicine occupies an important position due to its unique advantages. Among them, ephedra, scutellaria baicalensis seeds and perilla seeds are commonly used Chinese medicine combinations in clinical practice. Ephedra has a significant effect of clearing the lungs and relieving asthma. The ephedrine it contains can excite the β2 receptors of bronchial smooth muscles, effectively relax airway smooth muscles, and relieve wheezing and dyspnea caused by pneumonia. At the same time, it can inhibit the release of allergic mediators, reduce airway inflammatory reactions, and has a certain antipyretic effect. It is very suitable for children with pneumonia accompanied by fever, cough and asthma symptoms; scutellaria baicalensis seeds and perilla seeds can assist ephedra in enhancing the therapeutic effect.

[0003] However, the preparation process for traditional Chinese medicine compositions has significant shortcomings. Macromolecular impurities such as tannins contained in ephedra not only interfere with the proper efficacy of the drug but also pose two other problems: first, they can irritate children's delicate gastrointestinal tract, causing nausea, vomiting, and other discomfort; second, they can make the final composition taste bitter, significantly reducing children's medication compliance. Therefore, these substances must be removed as much as possible from children's preparations.

[0004] In view of this, the development of a preparation process that can not only efficiently extract the effective ingredients in traditional Chinese medicine compositions, but also significantly reduce the content of impurities such as tannins, and is simple to operate and suitable for industrial production has important clinical value and application significance. Summary of the Invention

[0005] The present invention aims to provide a traditional Chinese medicine composition for treating pediatric pneumonia and a preparation method thereof, aiming to solve the problems existing in the preparation process of the traditional Chinese medicine composition for treating pediatric pneumonia, such as low extraction rate of active ingredients and high content of impurities such as tannins. The specific preparation process is as follows:

[0006] A traditional Chinese medicine composition for treating pneumonia in children comprises, by weight, 10-20 parts of ephedra herb extract, 8-15 parts of scutellaria baicalensis seed extract, and 8-15 parts of perilla seed extract; and a flavoring agent is steviol glycoside or xylitol, wherein the flavoring agent accounts for 0.5-2wt% of the composition.

[0007] The preparation method of the Chinese medicine composition comprises the following steps:

[0008] S1. Raw material pretreatment: Grind the ephedra herb powder into 20-40 mesh coarse powder, dry it to a moisture content of ≤8wt%, and sieve it to remove sediment impurities and fine powder with a particle size of ≤20 mesh to obtain dry ephedra herb powder;

[0009] Among them, fine powder with a particle size of less than 20 mesh also needs to be eliminated because the overly fine hemp flower grass powder is more likely to precipitate tannins in subsequent operations.

[0010] S2. Supercritical fluid degreasing: Set the pressure to 25±0.2MPa, the carbon dioxide flow rate to 20±0.5L / h, and the extraction time to within 2 hours, preferably within 1.5 hours. The purpose of this step is to precipitate the fat-soluble impurities in ephedra. By increasing the pressure and reducing the extraction time, the extraction time is shortened, thereby reducing the precipitation of active ingredients such as ephedrine.

[0011] S3. Dynamic purification of solid matter:

[0012] A 60% ethanol aqueous solution is added to the solid matter in step S2. The ephedra powder obtained in step S2 is first placed on a sieve with a stacking height of 15-25 cm. The ethanol aqueous solution is extracted with a circulating pump to flush the ephedra powder. The temperature is gradually increased from 30° C. to 60° C. during the flushing, and the total flushing time is 2 h. Subsequently, the ephedra powder is immersed in the ethanol aqueous solution, stirred at a low speed at 60° C. to dissolve the active ingredient, and the extract is collected.

[0013] After supercritical treatment, the fiber structure of the ephedra powder becomes loose, which is already conducive to the precipitation of active ingredients such as ephedrine. However, to further reduce the precipitation treatment time and thus the amount of tannins dissolved, the fiber structure of the ephedra powder is further destroyed by flushing, and the ephedrine is gradually dissolved by increasing the temperature. This ensures that the ephedrine precipitation amount can reach approximately 90%, while also reducing the precipitation of tannins caused by long-term soaking.

[0014] S4, multi-stage membrane separation and purification:

[0015] Step 1: Microfiltration (MF) to remove suspended impurities

[0016] Microfiltration: The extract was passed through a 0.20-0.30 μm ceramic microfiltration membrane at a temperature of 40 ± 5 °C, a pressure of 0.1 ± 0.05 MPa, and a cross-flow velocity of 3 ± 0.2 m / s to remove suspended impurities.

[0017] Purpose: To remove suspended impurities such as drug residue particles and colloids in the extract to avoid clogging of subsequent ultrafiltration membranes.

[0018] Step 2: Ultrafiltration (UF) to remove macromolecular tannins

[0019] The microfiltration permeate was treated with a 3000±500Da polyethersulfone ultrafiltration membrane and concentrated 5 times at a temperature of 40±5°C and a pressure of 0.2±0.05MPa to remove large molecular tannins.

[0020] Principle: Ephedrine (molecular weight 165Da) can pass through the membrane, while tannins (molecular weight>1000Da), proteins and other large molecules are retained, and the tannin removal rate is ≥80%.

[0021] Step 3: Nanofiltration (NF) purification

[0022] The ultrafiltration permeate was treated with a 200±20Da composite nanofiltration membrane and further impurities were removed at a temperature of 35±5°C and a pressure of 0.5±0.05MPa.

[0023] Purpose: To further remove small molecule impurities (such as some monosaccharides and inorganic salts), improve the purity of ephedrine, and at the same time intercept residual small molecule tannins (molecular weight 500-1000Da).

[0024] The nanofiltration permeate is subjected to vacuum distillation and vacuum drying to obtain an ephedra extract having a tannin content of less than 0.1 wt %;

[0025] S5. Preparation: Add the scutellaria baicalensis fruit extract, the perilla fruit extract and the flavoring agent to the ephedra extract in step S4, and mix them evenly to prepare a composition.

[0026] In order to shorten the drying time and thus save the overall preparation cycle, the drying process in step S1 is hot air drying at a temperature of 60-80°C.

[0027] Furthermore, in step S3, the circulating pump flow rate is 10-15 L / h. When the stack height is 15-20 cm, a flow rate of 10-12 L / h ensures uniform penetration of the ethanol-water solution into the powder layer, preventing excessive tannin dissolution caused by localized fluid accumulation. When the stack height is 20-25 cm, increasing the flow rate to 13-15 L / h enhances the solution's flushing force, breaking through the resistance of the thicker powder layer, allowing ephedrine to fully dissolve under the temperature gradient (30°C to 60°C) while reducing active ingredient residue caused by poor circulation. The low-speed stirring speed is 30-50 rpm. This speed range promotes contact between the ephedra powder and the ethanol-water solution through gentle mechanical action, accelerating the dissolution of ephedrine from the loosened fiber structure, while also preventing excessive powder particle fragmentation caused by high-speed stirring. Excessive fragmentation can completely open the tannin release channels within the ephedra cells, resulting in increased tannin dissolution.

[0028] Furthermore, the preparation method of the scutellaria baicalensis seed extract and the perilla seed extract in step S5 is: crush the scutellaria baicalensis seed and the perilla seed respectively, reflux extract twice with 70% ethanol aqueous solution, combine the extracts, and concentrate under reduced pressure to a relative density of 1.10-1.15.

[0029] Furthermore, in step S5, the mass ratio of ephedra extract, scutellaria baicalensis seed extract, and perilla seed extract is 1:0.8-1.2:0.8-1.2.

[0030] Furthermore, during the dynamic purification process in step S3, 0.1-0.3 wt% of citric acid is added to the ethanol-water solution. Below 0.1 wt% may result in insufficient solution acidity, hindering effective polymerization of tannins. Above 0.3 wt% may cause ephedrine (alkaloids) to form complexes with other components due to excessive protonation, thereby reducing dissolution efficiency. The solution pH is gradually adjusted to a weakly acidic state over a period of 0.5-1 hour, with the pH adjustment rate strictly controlled during this process.

[0031] At this point, some of the dissolved tannins polymerize, producing a trace amount of precipitate. This precipitate is a macromolecular precipitate with a molecular weight of 5000 Da or greater. After removing the precipitate, slowly add sodium bicarbonate solution and adjust the pH to neutral. The resulting sodium citrate is a water-soluble organic acid salt without introducing inorganic impurities.

[0032] Furthermore, in the dynamic purification in step S3, the low-speed stirring is unidirectional rotation stirring, and the rotation direction is not changed during the process.

[0033] Beneficial effects:

[0034] Membrane separation technology enables molecular-level separation and purification, improving product purity. By reducing tannin content and adding flavoring agents, the traditional Chinese medicine composition has a favorable taste and is easy to swallow, significantly improving medication compliance among children. The application of these innovative processes has overcome the limitations of traditional Chinese medicine composition production, enhancing the quality and technical level of traditional Chinese medicine preparations. This achievement has a significant inhibitory effect, promoting improved pulmonary microcirculation in children and alleviating symptoms such as fever, cough, and asthma. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 The present invention is a process flow chart for preparing a traditional Chinese medicine composition for treating pneumonia in children;

[0036] Figure 2 It is a comparison chart of the detection of tannin content in Examples 1-3. DETAILED DESCRIPTION

[0037] In order to deepen the understanding of the present invention, the present invention will be further described in detail below with reference to embodiments and drawings. The embodiments are only used to explain the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0038] Example 1: A traditional Chinese medicine composition for treating pneumonia in children, comprising, by weight, 12 parts of Ephedra Herba Extract, 10 parts of Lepidium Immaturus Seed Extract, and 10 parts of Perilla Seed Extract, wherein steviol glycoside accounts for 0.8 wt % of the composition.

[0039] like Figure 1 As shown, the preparation method comprises the following steps:

[0040] S1. Raw material pretreatment: Crush the ephedra herb powder into 20-30 mesh coarse powder, dry it with 60°C hot air to a moisture content of 7 wt%, and sieve to remove sediment impurities and fine powder with a particle size of ≤20 mesh to obtain dry ephedra herb powder.

[0041] S2. Supercritical fluid degreasing: The ephedra powder obtained in step S1 was subjected to supercritical CO2 extraction at an extraction pressure of 25 MPa, a CO2 flow rate of 20 L / h, and an extraction time of 1.5 h, and the defatted solid matter was collected.

[0042] S3, dynamic purification: add 60% ethanol aqueous solution to the solid matter in step S2, place the ephedra powder on the sieve, stack it to a height of 15 cm, and use a circulating pump with a flow rate of 10 L / h to extract the ethanol aqueous solution for flushing, and the temperature is gradually increased from 30°C to 60°C, and the total flushing time is 2 hours; during the flushing process, citric acid is gradually added to the ethanol aqueous solution to adjust the pH value of the solution to weak acidity. At this time, the fixed precipitate produced by the flushing (including precipitated tannins and fine ephedra powder) is removed.

[0043] Subsequently, the ephedra powder was immersed in an ethanol aqueous solution and stirred in one direction at a low speed of 30 rpm at 60° C. to dissolve the active ingredient. During the process, sodium bicarbonate solution was added and gradually adjusted to neutral, and the extract was collected.

[0044] S4, multi-stage membrane separation and purification:

[0045] S41, microfiltration: the extract was passed through a 0.20 μm ceramic microfiltration membrane at a temperature of 35°C, a pressure of 0.05 MPa, and a cross-flow velocity of 2.8 m / s to remove suspended impurities;

[0046] S42, ultrafiltration: The microfiltration permeate was treated with a 2500Da polyethersulfone ultrafiltration membrane and concentrated 5 times at a temperature of 35°C and a pressure of 0.15 MPa;

[0047] S43, nanofiltration: The ultrafiltration permeate was treated with a 180Da composite nanofiltration membrane at a temperature of 30°C and a pressure of 0.45 MPa for further impurity removal;

[0048] S44. Vacuum treatment: The nanofiltration permeate is subjected to vacuum distillation and vacuum drying to obtain the ephedra extract.

[0049] S5. Preparation: Add the scutellaria baicalensis fruit extract, perilla fruit extract and steviol glycoside prepared according to the above method to the ephedra extract in step S4, and mix well to obtain the product.

[0050] Example 2: During the dynamic purification of S3, no weak acid or weak base was added, and the rest was the same as in Example 1.

[0051] Example 3:

[0052] A traditional Chinese medicine composition for treating pneumonia in children comprises, by weight, 18 parts of ephedra herb extract, 12 parts of scutellaria baicalensis seed extract, and 12 parts of perilla seed extract, wherein steviol glycoside accounts for 1.2 wt% of the composition.

[0053] like Figure 1 As shown, the preparation method comprises the following steps:

[0054] S1. Raw material pretreatment: Crush the ephedra herb powder into 30-40 mesh coarse powder, dry it with 60°C hot air to a moisture content of 8 wt%, and sieve to remove sediment impurities and fine powder with a particle size of ≤20 mesh to obtain dry ephedra herb powder.

[0055] The S2-S5 portion is consistent with that in Example 1.

[0056] Comparative Example: Using the decoction method: Mix the ingredients from Example 1, decoct twice (1 hour each time), concentrate, and add an equal amount of flavoring agent. Test results: ephedrine content 0.6wt%, tannin content 0.85wt%, and a bitter taste.

[0057] Content testing was performed on Examples 1-3. In Example 1, the ephedrine content was 1.3 wt %, and the tannin content was 0.07 wt %. In Example 2, the ephedrine content was 1.0 wt %, and the tannin content was 0.25 wt %. In Example 3, the ephedrine content was 1.2 wt %, and the tannin content was 0.06 wt %.

[0058] From the comparison between Example 1 and Example 3, it can be seen that when the particle size of the ephedra powder increases, the amount of tannin precipitation tends to decrease; although the ephedrine content decreases slightly at this time, it can still meet the treatment needs of pediatric pneumonia, and because there is less tannin residue, the taste of the composition is better.

[0059] Comparison of the test results of Example 1 and Example 2 shows that the tannin content can be significantly reduced by weak acid adjustment in the process of the present invention, but this step will cause a small amount of sodium citrate to remain in the extract and increase the raw material cost.

[0060] In summary, an adaptive process can be selected for different application scenarios: for the treatment of general pediatric pneumonia, the preparation process of Example 2 has a more significant cost advantage because it does not require acid-base adjustment; if there are higher requirements for taste, such as medication for young children, the process of Example 1 or 3 is more suitable. The composition prepared therefrom has a lower tannin content and a better taste, which can improve children's medication compliance.

[0061] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating pneumonia in children, characterized in that: By weight, the composition comprises 10-20 parts of Ephedra Herba extract, 8-15 parts of Lepidium Chinense seed extract and 8-15 parts of Perilla seed extract; and the flavoring agent accounts for 0.5-2wt% of the composition.

2. A Chinese medicine composition for treating pneumonia in children according to claim 1, characterized in that , the flavoring agent is steviol glycoside or xylitol.

3. A method for preparing a Chinese medicine composition for treating pneumonia in children, characterized in that , including the following steps: S1. Raw material pretreatment: Grind the ephedra herb powder into 20-40 mesh coarse powder, dry it to a moisture content of ≤8wt%, and sieve it to remove sediment impurities and fine powder with a particle size of ≤20 mesh to obtain dry ephedra herb powder; S2, supercritical fluid degreasing: The ephedra powder obtained in step S1 was subjected to supercritical CO2 extraction at an extraction pressure of 25 MPa, a CO2 flow rate of 20 L / h, and an extraction time of 1.5 h, and the defatted solid matter was collected; S3, dynamic purification: 60% ethanol aqueous solution was added to the solid matter of step S2, the ephedra powder obtained in S2 was first placed on a sieve, with a stacking height of 15-25 cm, and the ethanol aqueous solution was extracted with a circulating pump to flush the ephedra powder. The temperature during flushing was gradually raised from 30° C. to 60° C., and the total flushing time was 2 h; then the ephedra powder was immersed in the ethanol aqueous solution, stirred at a low speed at 60° C. to dissolve the active ingredient, and the extract was collected; S4, multi-stage membrane separation and purification: Microfiltration: The extract was passed through a 0.20-0.30 μm ceramic microfiltration membrane at a temperature of 40 ± 5 °C, a pressure of 0.1 ± 0.05 MPa, and a cross-flow velocity of 3 ± 0.2 m / s to remove suspended impurities. Ultrafiltration: The microfiltration permeate is treated with a 3000±500Da polyethersulfone ultrafiltration membrane and concentrated 5 times at a temperature of 40±5°C and a pressure of 0.2±0.05MPa to remove large molecular tannins. Nanofiltration: The ultrafiltration permeate is treated with a 200±20Da composite nanofiltration membrane and further removed at a temperature of 35±5°C and a pressure of 0.5±0.05MPa; Vacuum treatment: The nanofiltration permeate is subjected to vacuum distillation and vacuum drying to obtain an ephedra extract with a tannin content of less than 0.1 wt%; S5. Preparation: Add the scutellaria baicalensis fruit extract, the perilla fruit extract and the flavoring agent to the ephedra extract in step S4, and mix them evenly to prepare a composition.

4. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 3, wherein The drying process in step S1 is hot air drying at a temperature of 60-80°C.

5. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 4, characterized in that In step S3, the flow rate of the circulation pump is 10-15 L / h, and the speed of the low-speed stirring is 30-50 rpm.

6. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 4, characterized in that The preparation method of the scutellaria baicalensis seed extract and the perilla seed extract in step S5 is as follows: crush the scutellaria baicalensis seed and the perilla seed respectively, reflux extract twice with 70% ethanol aqueous solution, combine the extracts, and concentrate under reduced pressure to a relative density of 1.10-1.

15.

7. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 4, characterized in that In step S5, the mass ratio of ephedra extract, scutellaria baicalensis seed extract, and perilla seed extract is 1:0.8-1.2:0.8-1.

2.

8. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 4, characterized in that During the dynamic purification process in step S3, 0.1-0.3wt% of citric acid is added to the ethanol aqueous solution, and the pH value of the solution is gradually adjusted to weak acidity for 0.5-1h. At this time, some of the dissolved tannins undergo polymerization reaction to produce a small amount of precipitate. After removing the precipitate, sodium bicarbonate solution is slowly added to adjust the pH value to neutral.

9. The method for preparing a Chinese medicine composition for treating pneumonia in children according to claim 4, characterized in that ,During the dynamic purification in step S3, the low speed stirring is unidirectional ,rotational stirring, and the rotation direction is not changed during ,the process.

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