Children cough and asthma treating oral liquid and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to children cough and asthma oral liquid and a preparation method thereof, and the children cough and asthma oral liquid is prepared from the following raw materials in parts by weight: 30-50 parts of ephedra, 15-25 parts of asarum, 15-25 parts of cynanchum glaucescens, 5-15 parts of radix sophorae flavescentis and 5-15 parts of kaki calyx. According to the traditional Chinese medicine composition, by constructing a warm composition which takes the ephedra as the monarch, takes the asarum and the cynanchum glaucescens as the minister, and introduces the kaki calyx for reducing stomach qi and the radix sophorae flavescentis for resisting assistant, the problems that in the prior art, the pertinence on the infantile cold cough pathogenesis is not strong, and cold and cool medicine represses pathogenic qi are solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a pediatric cough and asthma relieving oral liquid and a preparation method thereof. BACKGROUND

[0002] The pediatric cough and asthma relieving oral liquid is a traditional Chinese medicine preparation widely used in pediatrics, mainly used for treating cough and asthma caused by exogenous wind-cold and phlegm turbidity blocking the lung in children. Most of the existing pediatric cough and asthma relieving oral liquids on the market are based on the classical theory of traditional Chinese medicine, and often use ephedra, bitter almond, gypsium and licorice as the core medicinal materials, aiming to promote the lung, clear heat and relieve asthma. These products have achieved certain curative effect in clinical practice and provide options for the treatment of pediatric respiratory diseases.

[0003] However, the existing pediatric cough and asthma relieving oral liquids, such as chuanbei pipa syrup and lung force cough mixture, still have some defects in the composition and preparation process. Most of the existing products are cool in nature and are mainly used for treating hot cough (symptoms: yellow and sticky sputum, dry mouth, sore throat), focusing on “promoting the lung and relieving asthma”, but often ignoring the key pathogenesis of “spleen deficiency” in children, which easily leads to “stomach qi reversal” and then drives the lung qi reversal. Many children with cough and asthma, especially in the early stage of the disease or children with weak constitution, show cold cough. Using cold and cool drugs for such patients will ice the evil qi, resulting in poor treatment effect on persistent and difficult-to-cure symptoms of cough and lack of targeted “stomach qi reversal to help lung qi reversal” medicinal material compatibility. Therefore, it is urgent to propose a pediatric cough and asthma relieving oral liquid and a preparation method thereof. SUMMARY

[0004] To solve the above problems, the present application provides a pediatric cough and asthma relieving oral liquid and a preparation method thereof, which solves the problems of poor targeting of existing technology for pediatric cold cough pathogenesis and ice evil qi of cold and cool drugs by constructing a warm composition with ephedra as the monarch, asarum and delphinium as the ministers, and introducing persimmon peel to reduce stomach qi and sophora to counteract.

[0005] To achieve the above purpose, the technical scheme of the present application is as follows: a pediatric cough and asthma relieving oral liquid is prepared from the following raw materials by weight: ephedra 30-50 parts, asarum 15-25 parts, delphinium 15-25 parts, sophora 5-15 parts and persimmon peel 5-15 parts.

[0006] Further, the following raw materials by weight are used: ephedra 30 parts, asarum 15 parts, delphinium 15 parts, sophora 5 parts and persimmon peel 5 parts.

[0007] Further, the following raw materials by weight are used: ephedra 40 parts, asarum 20 parts, delphinium 20 parts, sophora 10 parts and persimmon peel 10 parts.

[0008] Further, the following raw materials are used by weight: Ephedra 50 parts, Asarum 25 parts, Rehmannia 25 parts, Sophora 15 parts, and Persimmon Peel 15 parts.

[0009] A preparation method of a pediatric cough and asthma relieving oral liquid, based on the pediatric cough and asthma relieving oral liquid, comprises the following steps:

[0010] S1, extraction: the monarch drug Ephedra is extracted by ultrasonic-assisted water extraction, and the ministerial drugs Asarum and Rehmannia are extracted, to obtain a water extract; the auxiliary drugs Sophora and Persimmon Peel are extracted by microwave-assisted alcohol extraction, to obtain an alcohol extract;

[0011] S2, purification: the water extract and the alcohol extract obtained in S1 are combined, and then enriched and purified by a macroporous adsorption resin column, to collect a target eluate;

[0012] S3, refinement: the eluate obtained in S2 is filtered by a membrane separation system, to collect a filtrate;

[0013] S4, preparation: the filtrate obtained in S3 is concentrated, formulated, filled, sterilized, and then the pediatric cough and asthma relieving oral liquid is obtained.

[0014] Further, in S1, the ultrasonic-assisted water extraction is performed under the following conditions: the water amount is 8-12 times the total weight of the raw materials, the ultrasonic power is 300-500 W, the frequency is 25-40 kHz, the extraction temperature is 60-80℃, and the extraction time is 30-60 minutes; the microwave-assisted alcohol extraction is performed under the following conditions: the ethanol concentration is 50%-70%, the microwave power is 400-600 W, the extraction temperature is 60-75℃, and the extraction time is 10-20 minutes.

[0015] Further, in S2, the macroporous adsorption resin is AB-8 type, HPD-100 type, or D-101 type; the purification process includes sample loading, water washing, impurity removal, and elution with a 50%-70% ethanol solution, to collect an ethanol eluate.

[0016] Further, in S3, the membrane separation system is an inorganic ceramic membrane ultrafiltration system, and the membrane separation system has a membrane pore size of 50-100 nm and an operating pressure of 0.1-0.3 MPa.

[0017] Further, in S4, the concentration method is reduced-pressure concentration, and the temperature is controlled at 50-65℃, to concentrate the filtrate to a clear paste with a relative density of 1.05-1.15.

[0018] Further, the formulation method is as follows: a flavoring agent is added to the clear paste, and the flavoring agent is xylitol or steviol glycoside, and the amount of the flavoring agent added is 3%-5% or 0.01%-0.03% of the total volume of the oral liquid.

[0019] The above scheme has the following beneficial effects:

[0020] 1. This treatment plan uses ephedra as the principal ingredient. Ephedra is pungent, slightly bitter, and warm in nature, and excels at relieving exterior syndromes, dispersing cold, clearing the lungs, relieving cough, and calming asthma. It directly targets the core pathogenesis of wind-cold attacking the lungs and lung qi stagnation in children. The assistant ingredients, asarum and cynanchum, are both warm in nature. They work synergistically with ephedra to enhance the effects of dispelling wind and cold, warming the lungs and resolving phlegm, and lowering qi and resolving phlegm. This forms a synergistic effect of "clearing, dispersing, warming, and lowering," conforming to the classic treatment principle that "all diseases with phlegm should be treated with warm medicines." This fundamentally avoids the drawbacks of cold medicines suppressing pathogenic factors and aggravating the condition.

[0021] Building upon the synergistic effect of the principal and assistant herbs, the adjuvant herbs, persimmon calyx and sophora flavescens, introduce additional therapeutic dimensions. Persimmon calyx, addressing the common weakness of children's spleen and the tendency for stomach qi to rise and trigger lung qi, helps to lower lung qi by reducing stomach qi, thus resolving the root cause of persistent cough and achieving "treating both the lungs and stomach." Sophora flavescens, with its bitter and cold nature, counteracts the overall warming and drying properties of the formula, preventing damage to yin. Simultaneously, its anti-allergic effects, confirmed by modern research, alleviate airway hyperresponsiveness, providing an additional therapeutic advantage for children's coughs and wheezing induced by allergies. This combination not only strengthens the efficacy against cold-type coughs but also expands the therapeutic scope, enhancing the comprehensiveness and safety of the formula.

[0022] 2. This method, tailored to the characteristics of different medicinal materials, employs ultrasonic-assisted water extraction of the principal herb Ephedra and the assistant herbs Asarum and Cynanchum paniculatum, efficiently dissolving their pungent and warming dispersing components at low temperatures while avoiding high-temperature damage. Microwave-assisted alcohol extraction of the adjuvant herbs Sophora flavescens and persimmon calyx rapidly extracts alkaloids and flavonoids. Subsequent purification using macroporous adsorption resin and inorganic ceramic membrane ultrafiltration effectively enriches the active ingredients, removes impurities, and improves the clarity, stability, and bioavailability of the oral liquid, ensuring superior efficacy and more stable quality in the final product.

[0023] 3. This formula, through the counteracting effect of Sophora flavescens, introduces a balance of cold and cool properties on the basis of warmth, which not only targets the pathogenesis of cold cough but also prevents excessive warmth and dryness, making it suitable for children with immature Yin and Yang constitutions. At the same time, the stomach-lowering effect of persimmon calyx and the anti-allergic effect of Sophora flavescens solve the common problems of stomach qi reversal and allergic triggers in children's cough and asthma, so that the whole formula integrates modern medical understanding on the basis of classical theory, making it more clinically adaptable and practical. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the method steps in an embodiment of the present invention, namely, the Pediatric Cough and Asthma Relief Oral Liquid and its preparation method. Detailed Implementation

[0025] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0026] In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application. In addition, the terms "first", "second", "third" are only for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0027] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be broadly understood, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0028] The following will be further described in detail through specific embodiments:

[0029] Example 1:

[0030] A pediatric cough and asthma oral liquid is made from the following raw materials by weight: Ephedra 30-50 parts, Asarum 15-25 parts, Rehmannia 15-25 parts, Sophora 5-15 parts and persimmon 5-15 parts.

[0031] Example 2:

[0032] The difference from example 1 is that a pediatric cough and asthma oral liquid is made from the following raw materials by weight: Ephedra 30 parts, Asarum 15 parts, Rehmannia 15 parts, Sophora 5 parts and persimmon 5 parts.

[0033] Example 3:

[0034] The difference from example 2 is that a pediatric cough and asthma oral liquid is made from the following raw materials by weight: Ephedra 40 parts, Asarum 20 parts, Rehmannia 20 parts, Sophora 10 parts and persimmon 10 parts.

[0035] Example 4:

[0036] The difference from example 3 is that a pediatric cough and asthma oral liquid is made from the following raw materials by weight: Ephedra 50 parts, Asarum 25 parts, Rehmannia 25 parts, Sophora 15 parts and persimmon 15 parts.

[0037] Example 5:

[0038] As shown in the accompanying Figure 1The preparation method of the pediatric cough and wheezing oral liquid is different from that of Example 4, and is based on the pediatric cough and wheezing oral liquid described in Examples 1-4, and comprises the following steps:

[0039] S1, extraction: ultrasonic-assisted water extraction of the monarch drug ephedra, and extraction of the ministerial drugs asarum and impatiens balfourii to obtain water extract; microwave-assisted alcohol extraction of the auxiliary drugs sophora flavescens and persimmon calyx to obtain alcohol extract; the ultrasonic-assisted water extraction conditions are: water addition amount is 8-12 times the total weight of the raw materials, ultrasonic power is 300-500 W, frequency is 25-40 kHz, extraction temperature is 60-80℃, and extraction time is 30-60 minutes; the microwave-assisted alcohol extraction conditions are: ethanol concentration is 50%-70%, microwave power is 400-600 W, extraction temperature is 60-75℃, and extraction time is 10-20 minutes.

[0040] S2, purification: after the water extract and the alcohol extract obtained in S1 are combined, they are enriched and purified by a macroporous adsorption resin column, and the macroporous adsorption resin is AB-8 type, HPD-100 type or D-101 type; the purification process includes sample loading, water washing, impurity removal, and elution with 50%-70% ethanol solution, collection of the ethanol eluate, and collection of the target eluate;

[0041] S3, refining: the eluate obtained in S2 is filtered by a membrane separation system, and the membrane separation system is an inorganic ceramic membrane ultrafiltration system, the membrane separation system has a membrane pore size of 50-100 nm, and the operating pressure is 0.1-0.3 MPa; the filtrate is collected;

[0042] S4, preparation: the filtrate obtained in S3 is concentrated by vacuum concentration, and the temperature is controlled at 50-65℃; the clear paste with a relative density of 1.05-1.15 is obtained by concentration; the clear paste is adjusted by adding a flavoring agent and water, the flavoring agent is xylitol or steviol glycoside, and the amount of the flavoring agent added is 3%-5% or 0.01%-0.03% of the total volume of the oral liquid; the pediatric cough and wheezing oral liquid is obtained by sterilization after filling.

[0043] To evaluate the efficacy and safety of the pediatric cough and wheezing oral liquid prepared based on any weight part of Examples 1-4 and the pediatric cough and wheezing oral liquid prepared by the preparation method of Example 5 in treating pediatric cough and wheezing, the following experiments are designed to verify.

[0044] I. Grouping design

[0045] 1. Selection of subjects:

[0046] Inclusion criteria: age 2-12 years, diagnosed with acute bronchitis or asthmatic bronchitis, with cough, wheezing symptoms, course of disease ≤7 days, parents signed informed consent form.

[0047] 2. Exclusion criteria: allergic to traditional Chinese medicine ingredients, severe heart and lung diseases, immune deficiency, recent use of other cough and asthma drugs.

[0048] 3. Sample size: 200 patients were planned to be recruited and randomly divided into two groups, 100 patients in each group.

[0049] 4. Randomization and blinding: patients were divided into experimental and control groups using random number table method.

[0050] Experimental group: received pediatric cough and asthma oral liquid prepared according to the scheme (based on any of the formulations of examples 1-4, and produced according to the preparation method of example 5).

[0051] Control group: received pediatric cough and asthma oral liquid available on the market.

[0052] 5. Treatment plan:

[0053] Dose: adjusted according to age and weight, generally 5-10 mL each time, 3 times a day, oral.

[0054] 6. Course of treatment: 7 days.

[0055] 7. Basic care: both groups were given the same routine care (such as drinking water, rest), and other cough and asthma drugs were avoided.

[0056] II. Detection index

[0057] 1. Primary efficacy index:

[0058] Cough symptom score: 0-3 point scoring method (0 = no cough, 1 = mild, 2 = moderate, 3 = severe), record the frequency, intensity and duration of daytime and nighttime cough, evaluate before treatment, on the 3rd day of treatment and on the 7th day of treatment.

[0059] Wheezing symptom score: 0-3 point scoring method (0 = no wheezing, 1 = mild, 2 = moderate, 3 = severe), based on lung auscultation and patient complaints, assess the degree and frequency of wheezing, time points same as cough score.

[0060] 2. Secondary efficacy index:

[0061] 2.1 Overall efficacy evaluation: after treatment, the doctor assessed the clinical efficacy grade according to the improvement of symptoms:

[0062] Cure: symptom score reduction ≥95%.

[0063] Significant effect: symptom score reduction ≥70% but <95%.

[0064] Effective: Symptom score reduction ≥30% but <70%.

[0065] Ineffective: Symptom score reduction <30%.

[0066] 2.2 Lung function indicators: For children aged ≥6 years, PEF values ​​were measured using a peak expiratory flow (PEF) meter, once before treatment and once after treatment.

[0067] 2.3 TCM syndrome score: Based on the syndrome differentiation in the formula (such as wind-cold invading the lungs, phlegm retention), the improvement of related syndromes (such as phlegm volume, stomach qi rebellion) is evaluated.

[0068] 3. Safety indicators:

[0069] Adverse reaction monitoring: Record all adverse events (such as gastrointestinal reactions, rash, allergies, etc.) and assess their relevance to the drug.

[0070] Laboratory tests: Blood routine tests and liver and kidney function tests (ALT, AST, Cr) before and after treatment are used as a safety reference.

[0071] III. Conclusion

[0072] Based on the above grouping design and detection indicators, the experimental conclusions are as follows:

[0073] Efficacy: The improvement in cough and wheezing symptom scores in the experimental group was significantly better than that in the control group, indicating that this regimen has better efficacy in dispelling wind and warming the lungs, clearing phlegm and relieving cough.

[0074] Safety: The incidence of adverse reactions in the experimental group was lower than that in the control group, indicating that the protocol is safe.

[0075] Overall assessment: The formulation optimization and preparation methods (such as ultrasonic extraction and membrane separation purification) in the solution improved the dissolution and purity of the active ingredients.

[0076] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A pediatric cough and asthma relieving oral liquid, characterized in that, It is made from the following raw materials by weight: Ephedra 30-50 parts, Asarum 15-25 parts, Rehmannia 15-25 parts, Sophora 5-15 parts, and Kaki Calyx 5-15 parts.

2. The pediatric cough and asthma oral liquid according to claim 1, characterized in that, It is made from the following raw materials by weight: Ephedra 30 parts, Asarum 15 parts, Rehmannia 15 parts, Sophora 5 parts, and Kaki Calyx 5 parts.

3. The pediatric cough and asthma relieving oral liquid according to claim 1, characterized in that, It is made from the following raw materials by weight: Ephedra 40 parts, Asarum 20 parts, Rehmannia 20 parts, Sophora 10 parts, and Kaki Calyx 10 parts.

4. The pediatric cough and asthma relieving oral liquid according to claim 1, characterized in that, It is made from the following raw materials by weight: Ephedra 50 parts, Asarum 25 parts, Rehmannia 25 parts, Sophora 15 parts, and Kaki Calyx 15 parts.

5. A method for preparing the pediatric cough and asthma relieving oral liquid according to any one of claims 1-4, characterized in that, It comprises the following steps: S1, extraction: ultrasonic-assisted water extraction of the monarch drug Ephedra, and extraction of the ministerial drugs Asarum and Rehmannia, to obtain water extract; microwave-assisted alcohol extraction of the auxiliary drugs Sophora and Kaki Calyx, to obtain alcohol extract; S2, purification: combining the water extract and alcohol extract obtained in S1, and then enriching and purifying through a macroporous adsorption resin column to collect target eluate; S3, refining: filtering the eluate obtained in S2 using a membrane separation system to collect filtrate; S4, preparation: concentrating, dispensing, filling, and sterilizing the filtrate obtained in S3, to obtain the pediatric cough and asthma relieving oral liquid.

6. The preparation method of the pediatric cough and asthma oral liquid according to claim 5, characterized in that, In S1, the conditions for ultrasonic-assisted water extraction are as follows: water amount is 8-12 times the total weight of raw materials, ultrasonic power is 300-500 W, frequency is 25-40 kHz, extraction temperature is 60-80℃, and extraction time is 30-60 minutes; the conditions for microwave-assisted alcohol extraction are as follows: ethanol concentration is 50%-70%, microwave power is 400-600 W, extraction temperature is 60-75℃, and extraction time is 10-20 minutes.

7. The preparation method of the pediatric cough and asthma oral liquid according to claim 5, characterized in that, In S2, the macroporous adsorption resin is AB-8 type, HPD-100 type, or D-101 type; the purification process includes sample loading, water washing, impurity removal, and elution with 50%-70% ethanol solution to collect ethanol eluate.

8. The preparation method of the pediatric cough and asthma oral liquid according to claim 5, characterized in that, In S3, the membrane separation system is an inorganic ceramic membrane ultrafiltration system, the membrane separation system has a membrane pore size of 50-100 nm, and the operating pressure is 0.1-0.3 MPa.

9. The preparation method of the pediatric cough and asthma oral liquid according to claim 5, characterized in that, In S4, the concentration method is reduced pressure concentration, and the temperature is controlled at 50-65℃, and the concentration is performed until the relative density of the clear paste is 1.05-1.

15.

10. The preparation method of the pediatric cough and asthma oral liquid according to claim 5, characterized in that, In S4, the dispensing method is as follows: adding a flavoring agent and water to the clear paste, the flavoring agent is xylitol or steviol glycoside, and the amount of the flavoring agent added is 3%-5% or 0.01%-0.03% of the total volume of the oral liquid, respectively.

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