A traditional Chinese medicine oral gel for relieving wind-heat, clearing the lungs, stopping cough, and soothing the throat, and its preparation method.

Abstract

This invention provides a traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough, and soothing the throat, along with its preparation method. After combining the thick pastes, an impurity removal process is added, followed by refrigeration for at least 48 hours to remove some impurities and reduce the solid content. Then, by selecting 1.0%-2.5% xanthan gum as a matrix, and using 0.1%-0.2% Gannan orange flavoring and 0.2%-0.3% sucralose to form a complex flavoring system, and controlling the parameters during homogenization, this invention effectively solves the problems of poor gelation and instability in oral gel formulations. It also overcomes the bitter taste caused by the acidic and astringent odor of the drug extract and volatile oils. This invention features convenient administration, safety and effectiveness, good taste, and superior formulation stability, improving compliance for children and the elderly. The entire preparation method is simple and suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and in particular relates to a traditional Chinese medicine oral gel that relieves wind and lung congestion, stops cough and soothes the throat, and its preparation method. Background Technology

[0002] Suhuang Zhike Capsules are a widely used traditional Chinese medicine with the effects of dispelling wind and clearing the lungs, relieving cough and sore throat. It is mainly used to treat symptoms such as cough and itchy throat caused by wind-evil invading the lungs and impaired lung function. It has significant efficacy for post-cold cough and cough-variant asthma. The prescription contains nine medicinal materials, including ephedra, perilla leaf, earthworm, loquat leaf, stir-fried perilla seed, cicada slough, angelica root, stir-fried burdock seed, and schisandra fruit. Currently, commercially available Suhuang cough syrups are in hard capsule form, which has poor compliance for patients with swallowing difficulties (such as children, the elderly, or certain special medical conditions). Modern pharmaceutical research shows that gels, as a semi-solid dosage form, have unique advantages: their soft texture makes them easy to take orally, especially suitable for children and those with swallowing disorders. However, gels have poor stability and are prone to problems such as demulsification, layering, sudden changes in viscosity, and precipitation, affecting the uniformity of the formulation and making formulation molding difficult. In addition, the bitter and astringent tastes unique to traditional Chinese medicine herbs may result in unpleasant palatability for oral Chinese medicine gels.

[0003] To meet clinical needs, we plan to conduct dosage form improvement research and develop Suhuang cough-relieving oral gel with good medication adherence and safety. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine oral gel that relieves wind-cold, clears the lungs, stops cough, and soothes the throat, based on existing technology. After the thick paste is combined, an impurity removal process is added, followed by refrigeration for at least 48 hours to remove some impurities and reduce the solid content. Then, by selecting a specific amount of xanthan gum as a matrix, and using specific amounts of Gannan orange flavoring and sucralose to form a complex flavoring system, and by controlling the parameters during homogenization, the problems of poor gel formation and instability in oral gels are effectively solved. At the same time, the bitter taste caused by the acidic and astringent taste of the drug extract and the irritating odor of the volatile oils are overcome. This invention features convenient administration, safety and effectiveness, better taste, and superior formulation stability, improving compliance for children and the elderly. The entire preparation method is simple and suitable for large-scale industrial production.

[0005] Another object of the present invention is to provide a method for preparing the above-mentioned oral gel of traditional Chinese medicine.

[0006] The technical solution of the present invention is as follows: A traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough and soothing the throat, comprising extract, and / or volatile oil or its inclusion complex, matrix, antibacterial agent, sweetener and flavoring; The extract and / or volatile oil are prepared from the following components in parts by weight: Ephedra 4-6 parts, Perilla leaf 4-6 parts, Earthworm 4-6 parts, Honey loquat leaf 4-6 parts, Fried perilla seed 2-4 parts, Cicada slough 3-5 parts, Peucedanum praeruptorum 3-5 parts, Fried burdock seed 4-6 parts, Schisandra chinensis 3-5 parts.

[0007] In a preferred embodiment, the extract and / or volatile oil are prepared from the following components in parts by weight: 4.5-5.5 parts ephedra, 4.5-5.5 parts perilla leaf, 4.5-5.5 parts earthworm, 4.5-5.5 parts loquat leaf, 2.5-3.5 parts stir-fried perilla seed, 3.5-4.5 parts cicada slough, 3.5-4.5 parts angelica dahurica, 4.5-5.5 parts stir-fried burdock seed, and 3.5-4.5 parts schisandra chinensis.

[0008] In a more preferred embodiment, the extract and / or volatile oil are prepared from the following components in parts by weight: 5 parts ephedra, 5 parts perilla leaf, 5 parts earthworm, 5 parts loquat leaf, 3 parts stir-fried perilla seed, 4 parts cicada molting, 4 parts angelica root, 5 parts stir-fried burdock seed, and 4 parts schisandra fruit.

[0009] For the purposes of this invention, the matrix is ​​xanthan gum; the antibacterial agent is potassium sorbate and / or sodium benzoate, preferably potassium sorbate; the sweetener is sucralose, sucrose and / or steviol glycosides, preferably sucralose; and the flavoring is Gannan orange flavoring, pineapple flavoring, masking flavoring and / or mandarin orange flavoring, preferably Gannan orange flavoring.

[0010] The method for preparing oral gel of traditional Chinese medicine provided by the present invention includes the following steps: (1) Preparation of volatile oil: Soak perilla leaves and angelica root in water for 0.5-1.5 hours, distill to extract volatile oil for 4-10 hours, and collect the obtained volatile oil; (2) Preparation of volatile oil inclusion complex: Hydroxypropyl-β-cyclodextrin and purified water were mixed evenly, and the volatile oil obtained in step (1) was slowly added. The mixture was then ground to prepare the volatile oil inclusion complex. (3) Preparation of extract: I) Ephedra and Schisandra chinensis were extracted three times by reflux with 80% ethanol, each extraction time being 1-2 hours. The extracts were filtered, the filtrates were combined, the ethanol was recovered, and the extract was concentrated to a thick paste with a relative density of 1.25-1.30 at 50℃ for later use. II) Earthworm, loquat leaf, stir-fried perilla seed, cicada molting, and stir-fried burdock seed are decocted three times with water, each time for 0.5-1 hour. The decoction is filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.09-1.11 at 50°C. Ethanol is added to make the alcohol content reach 65-75%. The paste is first refrigerated, filtered, and the ethanol is recovered. The paste is then concentrated to a thick paste with a relative density of 1.25-1.30 at 50°C. This paste is then combined with the thick paste obtained in step I), refrigerated again, and filtered to obtain the extract. (4) Gel preparation: a) Xanthan gum was added to purified water and swollen to obtain a matrix solution; b) Add the extract obtained in step (3), the volatile oil inclusion complex obtained in step (2), the antibacterial agent, the sweetener and the fragrance to the matrix solution, stir evenly, add purified water to make up the volume, vacuum, homogenize and degas to obtain the gel.

[0011] For the purposes of this invention, the total amount of Chinese medicinal materials refers to the medicinal materials used to prepare the extract and / or volatile oil, including the total amount of nine medicinal materials: ephedra, perilla leaf, earthworm, loquat leaf, stir-fried perilla seed, cicada slough, angelica root, stir-fried burdock seed, and schisandra fruit. Taking the total amount of the gelling agent as 100%, the addition amount of the total amount of Chinese medicinal materials is 55%-95%, preferably 65%-85%, and more preferably 74%-75%.

[0012] In this invention, in step (4), the amount of xanthan gum added is 1.0%-2.5% based on the total amount of gelling agent being 100%, preferably, the amount of xanthan gum added is 1.5%.

[0013] In step (4), the antibacterial agent is potassium sorbate, which is 100% of the total amount of gelling agent; the amount added is 0.1%-1.0%, preferably 0.15-0.25%, and more preferably 0.2%, based on 100% of the total amount of gelling agent.

[0014] In step (4), the sweetener is sucralose, which is 100% of the total amount of gelling agent; the amount added is 0.1%-1.0%, preferably 0.2-0.3%, and more preferably 0.2%, based on 100% of the total amount of gelling agent.

[0015] In step (4), the fragrance is Gannan orange fragrance, which is 100% of the total amount of gelling agent; the amount added is 0.05%-0.5%, preferably 0.1-0.2%, and more preferably 0.1%, based on 100% of the total amount of gelling agent.

[0016] In step (4), when evacuating, the vacuum level is controlled to be 150 mbar-250 mbar, preferably 200 mbar.

[0017] In step (4), during homogenization, the control parameters are as follows: The homogenization speed is 2000-2200 rpm, which can be but is not limited to 2000 rpm, 2050 rpm, 2100 rpm, 2150 rpm or 2200 rpm, with 2100 rpm being preferred.

[0018] The number of homogenizations is 2-4 times, but it is not limited to 2, 3 or 4 times.

[0019] The homogenization process is preferably repeated 3 times; the homogenization time is 3-10 minutes, which can be, but is not limited to, 3 minutes, 5 minutes, 8 minutes or 10 minutes, but is preferably 5 minutes.

[0020] In this invention, in step (1), the soaking time is 1 hour and the extraction time is 8 hours.

[0021] In this invention, in step (2), the weight ratio of hydroxypropyl-β-cyclodextrin to purified water is 1:0.2-1.5, preferably 1:0.5-1.0; more preferably, the weight ratio of hydroxypropyl-β-cyclodextrin to purified water is 1:0.7-0.8.

[0022] In step (2), the volume weight ratio of volatile oil to hydroxypropyl-β-cyclodextrin is 1:5-15 mL / g, preferably 1:10-12 mL / g.

[0023] For the purposes of this invention, in step I) of extract preparation, the extraction time for each extraction is 1.5 hours.

[0024] In step II) of extract preparation, each decoction is performed for 1 hour; ethanol is added until the alcohol content reaches 70%.

[0025] In step II) of extract preparation, the initial refrigeration time is 24 hours or more.

[0026] In step II) of extract preparation, the sample is refrigerated again for 48 hours or more.

[0027] Given that the original dosage form has been on the market for many years with significant efficacy and has been widely used in clinical practice among children, in order to expand the pediatric indication population and increase compliance, this invention provides an oral gel.

[0028] The oral gel provided by this invention uses xanthan gum as a matrix. The extract, volatile oil inclusion complex, xanthan gum, antibacterial agent, sweetener, and flavoring are stirred evenly, then vacuum-sealed, homogenized, and degassed to form a gel. By controlling the parameters during the homogenization process, the invention effectively solves the problems of poor gelation and instability in oral gels. It also overcomes the bitter taste caused by the acidity of the drug extract and the pungent odor of the volatile oil. This invention features convenient administration, safety and effectiveness, better taste, and superior formulation stability, improving compliance for children and the elderly. The entire preparation method is simple and suitable for large-scale industrial production.

[0029] The beneficial effects of this invention are as follows: 1. An impurity removal process is added. By refrigerating the thick paste again for more than 48 hours, some impurities are removed, the solid content is reduced, making it easier to mold and more stable.

[0030] 2. Select a specific amount of 1.0%-2.5% xanthan gum as the matrix to ensure that the properties meet the requirements and the stability is good.

[0031] 3. By optimizing the homogenization parameters, the optimal number of homogenizations is 3, the homogenization time for each homogenization is 5 minutes, and the homogenization speed is 2000-2200 rpm, thereby improving the stability of the gel.

[0032] 4. Selecting a specific amount of 0.1%-0.2% Gannan orange flavoring and 0.2%-0.3% sucralose in a specific ratio can significantly improve the taste of the gelling agent. Detailed Implementation

[0033] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims. Example 1

[0034] A traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough and soothing the throat is prepared at 1.5 times the daily dose. The extract and / or volatile oil are prepared from the following components: Ephedra 7.5 g, Perilla leaf 7.5 g, Earthworm 7.5 g, Loquat leaf 7.5 g, Fried Perilla seed 4.5 g, Cicada slough 6 g, Peucedanum praeruptorum 6 g, Fried Arctium lappa seed 7.5 g, Schisandra chinensis 6 g; The preparation method of the gelling agent includes the following steps: (1) Preparation of volatile oil: Take 7.5 g of perilla leaves and 6 g of angelica root, soak them in water for 1 hour, distill to extract volatile oil for 8 hours, and collect the obtained volatile oil; (2) Preparation of volatile oil inclusion complex: Hydroxypropyl-β-cyclodextrin and purified water were mixed evenly, and the volatile oil-ethanol solution prepared by dispersing the volatile oil obtained in step (1) into ethanol was slowly added. The volume ratio of volatile oil to ethanol was 1:1. The mixture was ground for 20 minutes to prepare the volatile oil inclusion complex. The weight ratio of hydroxypropyl-β-cyclodextrin to purified water was 1:0.75, and the volume weight ratio of volatile oil to hydroxypropyl-β-cyclodextrin was 1:12 mL / g. (3) Preparation of the extract, including the following steps: I) Add 7.5g of ephedra and 6g of schisandra to 80% ethanol, reflux and extract three times, each extraction time is 1.5 hours, filter, combine the filtrates, recover the ethanol, and concentrate to a thick paste with a relative density of 1.29 at 50℃, for later use; II) 7.5g of earthworm, 7.5g of loquat leaf, 4.5g of stir-fried perilla seed, 6g of cicada molting, and 7.5g of stir-fried burdock seed were decocted three times with water, one hour each time. The decoction was filtered, and the filtrate was concentrated to a thick paste with a relative density of 1.10 at 50°C. Ethanol was added to make the alcohol content reach 70%. The paste was first refrigerated for 24 hours, filtered, and the ethanol was recovered. The paste was then concentrated to a thick paste with a relative density of 1.28 at 50°C. The paste was then combined with the thick paste obtained in step I), refrigerated again for 48 hours, and filtered to obtain the extract. (4) Preparation of the gelling agent, including the following steps: a) Add 1.2g (1.5%) xanthan gum to 24g purified water to swell and obtain a matrix solution; b) Add the extract obtained in step (3), the volatile oil inclusion complex obtained in step (2), 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, add purified water to make up to 81 g. Vacuum the solution and control the vacuum degree to 200 mbar. Then homogenize the solution. Control the homogenization speed to 2100 rpm, homogenize 3 times, and homogenize for 5 minutes. After homogenization, stir at 60 rpm and degas while stirring for 25 minutes to obtain the gel.

[0035] Comparative Example 1 Compared to Example 1, the second refrigeration process is reduced, while the rest remains the same.

[0036] Comparative Example 2 Compared to Example 1, the re-refrigeration time was changed to 24 hours.

[0037] Comparative Example 3 Compared to Example 1, the re-refrigeration time was changed to 72 hours.

[0038] Experimental Example 2: Comparison of the effects of different purification processes on properties Using traits and particle size as evaluation indicators, the results are shown in Table 1 below.

[0039] Table 1. Refrigeration Study of Thick Paste

[0040] As shown in Table 1, the thick paste contains a lot of particulate matter in the gel without refrigeration, and the particle size does not meet the requirements. The particle size standard is not greater than 180μm. Therefore, it is determined that the thick paste needs to be refrigerated again.

[0041] Experiment Example 3: Investigation of the Refrigeration Time of Thick Paste Using traits and particle size as evaluation indicators, the results are shown in Table 2 below.

[0042] Table 2. Investigation of the refrigeration time of thick paste

[0043] As shown in Table 2, the gel properties of the thick paste were good after being refrigerated for 24h, 48h, and 72h. However, the particle size was 206 μm after refrigeration for 24h, which does not meet the requirement that the particle size should not exceed 180 μm. The properties and particle size of the thick paste met the requirements after refrigeration for 48h and 72h. Therefore, the refrigeration time of the thick paste was determined to be 48h or more.

[0044] Experimental Example 4: Comparison of the effects of different matrices and dosages on properties A traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough and soothing the throat is prepared at 30 times the daily dose. The extract and / or volatile oil are prepared from the following components: Ephedra 150 g, Perilla leaf 150 g, Earthworm 150 g, Loquat leaf 150 g, Fried Perilla seed 90 g, Cicada slough 120 g, Peucedanum praeruptorum 120 g, Fried burdock seed 150 g, Schisandra chinensis 120 g. The preparation method of the gelling agent includes the following steps: (1) Preparation of volatile oil: Take 150 g of perilla leaves and 120 g of angelica root, soak them in water for 1 hour, distill to extract volatile oil for 8 hours, and collect the obtained volatile oil; (2) Preparation of volatile oil inclusion complex: Hydroxypropyl-β-cyclodextrin and purified water were mixed evenly, and the volatile oil-ethanol solution prepared by dispersing the volatile oil obtained in step (1) into ethanol was slowly added. The volume ratio of volatile oil to ethanol was 1:1. The mixture was ground for 20 minutes to prepare the volatile oil inclusion complex. The mixture was divided into 20 equal parts for later use. The weight ratio of hydroxypropyl-β-cyclodextrin to purified water was 1:0.75, and the volume weight ratio of volatile oil to hydroxypropyl-β-cyclodextrin was 1:12 mL / g. (3) Preparation of the extract, including the following steps: I) Add 150g of ephedra and 120g of schisandra to 80% ethanol, reflux and extract three times, each extraction time is 1.5 hours, filter, combine the filtrates, recover the ethanol, and concentrate to a thick paste with a relative density of 1.29 at 50℃, for later use; II) 150g of earthworm, 150g of loquat leaf, 90g of stir-fried perilla seed, 120g of cicada molting, and 150g of stir-fried burdock seed are decocted three times with water, one hour each time. The decoction is filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.10 at 50°C. Ethanol is added to make the alcohol content reach 70%. The paste is first refrigerated for 24 hours, filtered, the ethanol is recovered, and the paste is concentrated to a thick paste with a relative density of 1.28 at 50°C. The paste is then combined with the thick paste obtained in step I), refrigerated again for 48 hours, filtered, and the extract is obtained. The extract is divided into 20 equal portions for later use. The following six matrices were examined: Carbomer A, Carbomer B, Carbomer C, Sodium alginate, Xanthan gum, and a composite (Sodium alginate + Agar), with properties, particle size, and stability as evaluation indicators.

[0045] Stability test: The test samples were sealed in brown oral pharmaceutical polyester bottles, with 3 samples in each group. After being placed under high temperature (45℃) and low temperature (4℃) conditions for 10 days, the state of the test samples was observed.

[0046] Matrix-Carbomer Type A

[0047] The gel was prepared according to the preparation method in Example 1. The dosages of 0.5% (0.4g), 1% (0.8g), 1.5% (1.2g), 2.0% (1.6g), and 2.5% (2.0g) of carbomer A were investigated. Taking 0.5% (0.4g) of carbomer A as an example.

[0048] a) Add 0.5% (0.4g) of carbomer A to 8.0g of purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, the pH value is measured to be 3.6. Adjust the pH value to 6.0 with triethanolamine, add purified water to make up to 81 g, evacuate and control the vacuum degree to 200 mbar, then homogenize, control the homogenization speed to 2100 rpm, homogenize 3 times, and homogenize for 5 minutes. After homogenization, stir at 60 rpm and degas at the same time for 25 minutes to obtain the gel.

[0049] The difference between the gels made with different amounts of carbomer A (0.5% (0.4g), 1% (0.8g), 1.5% (1.2g), 2.0% (1.6g), and 2.5% (2.0g) lies in the amount of carbomer A added when preparing the matrix solution, and the amount of purified water added is 20 times that of carbomer A.

[0050] Matrix-Carbomer Type B

[0051] The gel was prepared according to the preparation method in Example 1, and the dosage of 1.5% (1.2g) carbomer type B was investigated.

[0052] a) Add 0.5% (0.4g) of carbomer type B to 8.0g of purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavor to the obtained matrix solution. After stirring evenly, the pH value is measured to be 3.6. Adjust the pH value to 6.2 with triethanolamine, add purified water to make up to 81 g, evacuate the vacuum and control the vacuum degree to 200 mbar, then homogenize, control the homogenization speed to 2100 rpm, homogenize 3 times, and homogenize for 5 minutes. After homogenization, stir at 60 rpm and degas at the same time for 25 minutes to obtain the gel.

[0053] Matrix-Carbomer C

[0054] The gel was prepared according to the preparation method in Example 1, and the dosage of 1.5% (1.2g) carbomer C was investigated.

[0055] a) Add 0.5% (0.4g) of carbomer C to 8.0g of purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavor to the obtained matrix solution. After stirring evenly, the pH value is measured to be 3.6. Adjust the pH value to 6.2 with triethanolamine, add purified water to make up to 81 g, evacuate the vacuum and control the vacuum degree to 200 mbar, then homogenize, control the homogenization speed to 2100 rpm, homogenize 3 times, and homogenize for 5 minutes. After homogenization, stir at 60 rpm and degas at the same time for 25 minutes to obtain the gel.

[0056] Matrix - Sodium Alginate

[0057] The gel was prepared according to the preparation method in Example 1. The dosages of sodium alginate were investigated at 0.4% (0.32g), 0.6% (0.48g), 0.8% (0.64g), 1.2% (0.96g), and 1.4% (1.12g), respectively. Taking 0.4% (0.32g) sodium alginate as an example.

[0058] a) Add 0.4% (0.32g) sodium alginate to 6.4g purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, add purified water to make up to 81 g. Vacuum the solution and control the vacuum degree to 200 mbar. Then homogenize the solution at a speed of 2100 rpm for 3 times and for 5 minutes. After homogenization, stir at 60 rpm and degas the solution for 25 minutes to obtain the gel.

[0059] The difference between the gels made with different amounts of sodium alginate (0.4% (0.32g), 0.6% (0.48g), 0.8% (0.64g), 1.2% (0.96g), and 1.4% (1.12g) lies in the amount of sodium alginate added when preparing the matrix solution, and the amount of purified water added is 20 times the amount of sodium alginate added.

[0060] Matrix - xanthan gum

[0061] The gel was prepared according to the preparation method in Example 1, and the dosages of xanthan gum were investigated at 0.5% (0.4g), 1% (0.8g), 1.5% (1.2g, i.e., Example 1), 2.0% (1.6g), and 2.5% (2.0g). The 0.5% (0.4g) xanthan gum dosage was taken as an example.

[0062] a) Add 0.5% (0.4 g) xanthan gum to 8.0 g purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, add purified water to make up to 81 g. Vacuum the solution and control the vacuum degree to 200 mbar. Then homogenize the solution at a speed of 2100 rpm for 3 times and for 5 minutes. After homogenization, stir at 60 rpm and degas the solution for 25 minutes to obtain the gel.

[0063] The differences between the gels prepared with different amounts of xanthan gum (0.5% (0.4g), 1% (0.8g), 2.0% (1.6g), and 2.5% (2.0g) lie in the amount of xanthan gum added when preparing the matrix solution, and the amount of purified water added is 20 times the amount of xanthan gum added. Example 1 uses 1.5% (1.2g) xanthan gum.

[0064] The different substrates and dosages were investigated as shown in Table 3.

[0065] Table 3. Different substrates and dosage numbers

[0066] The results, using properties, particle size, and stability as evaluation indicators, are shown in Table 4 below.

[0067] Table 4 Results of the investigation of different matrices and dosages

[0068] Experimental results showed that when sodium alginate was used as the matrix, the sample had poor formability and its properties did not meet the requirements. When carbomer A, carbomer B, and carbomer C were used as the matrix, the sample stability and properties did not meet the requirements. When 0.5%-2.5% xanthan gum was used as the matrix, the properties, particle size, and stability all met the requirements. Therefore, xanthan gum was selected as the matrix. Composite matrix investigation

[0069] Following the preparation method in Example 1, the following preparations were investigated: 0.5% (0.4 g) sodium alginate and 1.0% (0.8 g) agar, 0.5% (0.4 g) carrageenan and 1.2% (0.96 g) gelatin, and 0.5% (0.4 g) carrageenan and 1.0% (0.8 g) xanthan gum. The preparation of 0.5% (0.4 g) sodium alginate and 1.0% (0.8 g) agar was used as an example.

[0070] a) Add 0.5% (0.4g) sodium alginate and 1.0% (0.8g) agar to 24g purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, add purified water to make up to 81 g. Vacuum the solution and control the vacuum degree to 200 mbar. Then homogenize the solution at a speed of 2100 rpm for 3 times and for 5 minutes. After homogenization, stir at 60 rpm and degas the solution for 25 minutes to obtain the gel.

[0071] The differences between the gels made from 0.5% (0.4g) sodium alginate and 1.0% (0.8g) agar, 0.5% (0.4g) carrageenan and 1.2% (0.96g) gelatin, and 0.5% (0.4g) carrageenan and 1.0% (0.8g) xanthan gum lie in the different matrix combinations used when preparing the matrix solution. Specifically, the solutions for 0.5% (0.4g) sodium alginate and 1.0% (0.8g) agar have 24g of purified water added; the solutions for 0.5% (0.4g) carrageenan and 1.2% (0.96g) gelatin have 27.2g of purified water added; and the solutions for 0.5% (0.4g) carrageenan and 1.0% (0.8g) xanthan gum have 24g of purified water added.

[0072] The different matrix combinations and dosages investigated are shown in Table 5.

[0073] Table 5. Different matrix combinations and dosages

[0074] The results, using properties, particle size, and stability as evaluation indicators, are shown in Table 6 below.

[0075] Table 6 Results of the investigation of different matrix combinations and dosages

[0076] The composite matrix did not meet the requirements for properties and stability. No. 18 was prone to separation due to insufficient viscosity, while Nos. 19 and 20 had poor formability due to their high viscosity, which was close to solid.

[0077] Experimental Example 5: Investigation of Homogeneity Parameters A traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough and soothing the throat is prepared at 12 times the daily dose. The extract and / or volatile oil are prepared from the following components: Ephedra 60 g, Perilla leaf 60 g, Earthworm 60 g, Loquat leaf 60 g, Fried Perilla seed 36 g, Cicada slough 48 g, Peucedanum praeruptorum 48 g, Fried Arctium lappa seed 60 g, Schisandra chinensis 48 g. (1) Preparation of volatile oil: Take 60 g of perilla leaves and 48 g of angelica root, soak them in water for 1 hour, distill to extract volatile oil for 8 hours, and collect the obtained volatile oil; (2) Preparation of volatile oil inclusion complex: Hydroxypropyl-β-cyclodextrin and purified water were mixed evenly, and the volatile oil-ethanol solution prepared by dispersing the volatile oil obtained in step (1) into ethanol was slowly added. The volume ratio of volatile oil to ethanol was 1:1. The mixture was ground for 20 minutes to prepare the volatile oil inclusion complex, which was divided into 8 equal parts for later use. The weight ratio of hydroxypropyl-β-cyclodextrin to purified water was 1:0.75, and the volume weight ratio of volatile oil to hydroxypropyl-β-cyclodextrin was 1:12 mL / g. (3) Preparation of the extract, including the following steps: I) Add 60g of ephedra and 48g of schisandra to 80% ethanol, reflux and extract three times, each extraction time is 1.5 hours, filter, combine the filtrates, recover the ethanol, and concentrate to a thick paste with a relative density of 1.29 at 50℃, for later use; II) 60g of earthworm, 60g of loquat leaf, 36g of stir-fried perilla seed, 48g of cicada molting, and 60g of stir-fried burdock seed are decocted three times with water for 1 hour each time. The decoction is filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.10 at 50°C. Ethanol is added to make the alcohol content reach 70%. The paste is first refrigerated for 24 hours, filtered, the ethanol is recovered, and the paste is concentrated to a thick paste with a relative density of 1.28 at 50°C. The paste is then combined with the thick paste obtained in step I), refrigerated again for 48 hours, filtered, and the extract is obtained. The extract is divided into 8 equal portions for later use. (4) Preparation of the gelling agent, including the following steps: a) Add 1.2g (1.5%) xanthan gum to 24g purified water to swell and obtain a matrix solution; b) Add 1 part of extract, 1 part of volatile oil inclusion complex, 0.16 g (0.2%) potassium sorbate, 0.16 g (0.2%) sucralose and 0.08 g (0.1%) Gannan orange flavoring to the obtained matrix solution. After stirring evenly, add purified water to make up to 81 g. Vacuum the solution and control the vacuum degree to 200 mbar to obtain the homogenized mixed solution. Prepare a total of 8 solutions in the same way and investigate the effect of different homogenization parameters on the gelling agent.

[0078] Homogenization time study

[0079] Take two portions of the above-mentioned homogenized solution and homogenize them again. Control the homogenization speed at 2100 rpm and homogenize three times. Observe the homogenization time at 2 minutes and 8 minutes respectively. After homogenization, stir at 60 rpm and degas simultaneously for 25 minutes to obtain the gel. The homogenization time is 5 minutes, which is Example 1. Homogenization test

[0080] Take two portions of the above-mentioned homogenized solution and homogenize them again. Control the homogenization speed at 2100 rpm and the homogenization time at 5 minutes. Observe the number of homogenization cycles, which are 1 and 2 times respectively. After homogenization, stir at 60 rpm and degas simultaneously for 25 minutes to obtain the gel. The homogenization cycle is 3 times, which is Example 1. Homogeneous rotation speed test

[0081] Take four portions of the above-mentioned homogenized solution and homogenize them again. The homogenization process is controlled to be three times, with a homogenization time of 5 minutes. Different homogenization speeds of 1600 rpm, 1800 rpm, 2000 rpm, and 2200 rpm are investigated. After homogenization, stir at 60 rpm while degassing for 25 minutes to obtain the gelling agent. The homogenization speed of 2100 rpm corresponds to Example 1.

[0082] Using traits and particle size as evaluation indicators, the results are shown in Table 7 below.

[0083] Table 7 Homogeneity Parameter Investigation

[0084] As shown in Table 7, after homogenization for 2 minutes, the gel-like colloid has good gloss, is relatively fine, contains small air bubbles, and has a particle size greater than 180 μm, which does not meet the requirements. After homogenization for 5 minutes and 8 minutes, the gel-like colloid has good gloss, is fine, has no obvious air bubbles, and the particle size meets the requirements, with no significant difference. Therefore, the homogenization time is determined to be 5 minutes.

[0085] Homogenization once resulted in a gel with good gloss, a fine texture, small air bubbles, and a particle size greater than 180 μm, which did not meet the requirements. Homogenization three times resulted in a gel with good gloss, a fine texture, and no obvious air bubbles, which was better than homogenization twice. The particle size was less than 180 μm. Therefore, the homogenization time was determined to be three times.

[0086] The homogenization speed test showed that as the homogenization speed increased, the particle size became smaller, but all met the requirements. A small number of small bubbles appeared at a speed of 1600 rpm, and the properties were better at a speed of 1800-2200 rpm than at a speed of 1600 rpm. Therefore, the homogenization speed was determined to be 1800-2200 rpm.

[0087] Experiment Example 6: The Effect of Type and Amount of Flavorings and Sweeteners on Taste Compared to Example 1, the 0.08g (0.1%) Gannan orange flavoring in Example 1 was replaced with four flavorings: pineapple flavoring, masking flavoring, and mandarin orange flavoring. Different gelling agents were prepared by using these flavorings at proportions of 0.05%, 0.1%, and 0.2%. The 0.16g (0.2%) sucralose was replaced by gelling agents prepared at proportions of 0.1%, 0.2%, and 0.3% sucralose; sucrose was prepared at proportions of 5%, 10%, and 15%; and steviol glycosides were prepared at proportions of 0.2%, 0.4%, and 0.6%. Investigation on the types and amounts of flavorings and sweeteners

[0088] Four flavorings—pineapple flavoring, masking flavoring, Gannan orange flavoring, and mandarin orange flavoring—and three sweeteners—sucralose, sucrose, and steviol glycosides—were examined, and a comprehensive evaluation was conducted based on five aspects: sourness, bitterness, sweetness, saltiness, and volatile oil flavor.

[0089] Table 8. Examination of the Types and Dosages of Flavorings and Sweeteners Volunteer sensory evaluation

[0090] Volunteers rated the sourness, bitterness, sweetness, saltiness, and volatile oil flavor of the samples shown in Table 8 according to the taste evaluation criteria. The total score was 25 points. The higher the score, the better the flavor correction effect of the formula. A score of more than 20 points indicated that the sample tasted good and was acceptable.

[0091] Table 9. Volunteer oral evaluation scores

[0092] The results are shown in Table 9. The optimal ratio of sweetener (0.2%-0.3% sucralose) to flavoring (0.1%-0.2% Gannan orange flavoring) was found to be the best. Other ratios of sweetener and flavoring resulted in poor taste improvement.

[0093] Experiment Example 7 Stability Test The gels prepared with different amounts of xanthan gum (0.5% (0.4g), 1% (0.8g), 1.5% (1.2g, i.e., Example 1), 2.0% (1.6g), and 2.5% (2.0g) as described in Example 4 were tested. The gels prepared with different homogenization speeds (1600 rpm, 1800 rpm, 2000 rpm, 2000 rpm (Example 1), and 2200 rpm) as described in Example 5 were tested under accelerated conditions (temperature 30℃±2℃, relative humidity 65%±5%). The results after 12 months are shown in the table below.

[0094] Table 10. Stability study results at different xanthan gum dosages (accelerated conditions)

[0095] Table 11. Stability test results at different homogeneous rotational speeds (acceleration conditions)

[0096] The stability test results showed that the gelling agent with 0.5% xanthan gum as the matrix did not meet the requirements in terms of properties after 9 months of accelerated curing, exhibiting stratification. The gelling agent with 1.0%-2.5% xanthan gum as the matrix met all requirements under accelerated curing conditions, with no significant changes. Therefore, 1.0%-2.5% xanthan gum as the matrix is ​​preferred. The gelling agent with a homogenization speed of 1800 rpm did not meet the requirements in terms of properties after 12 months of accelerated curing, exhibiting stratification. The gelling agent with a homogenization speed of 2000-2200 rpm met all requirements under accelerated curing conditions, with no significant changes. Therefore, a homogenization speed of 2000-2200 rpm is preferred.

[0097] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine oral gel for relieving wind-heat, clearing the lungs, stopping cough, and soothing the throat, characterized in that... This includes extracts, and / or volatile oils or their inclusion compounds, bases, antibacterial agents, sweeteners, and flavorings; The extract and / or volatile oil are prepared from the following components in parts by weight: Ephedra 4-6 parts, Perilla leaf 4-6 parts, Earthworm 4-6 parts, Honey loquat leaf 4-6 parts, Fried perilla seed 2-4 parts, Cicada slough 3-5 parts, Peucedanum praeruptorum 3-5 parts, Fried burdock seed 4-6 parts, Schisandra chinensis 3-5 parts; The matrix is ​​xanthan gum; the antibacterial agent is potassium sorbate and / or sodium benzoate; the sweetener is sucralose, sucrose and / or steviol glycosides; and the flavoring is Gannan orange flavoring, pineapple flavoring, masking flavoring and / or mandarin orange flavoring.

2. The traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough, and soothing the throat according to claim 1, characterized in that, The extract and / or volatile oil were prepared from the following components in parts by weight: 4.5-5.5 parts ephedra, 4.5-5.5 parts perilla leaf, 4.5-5.5 parts earthworm, 4.5-5.5 parts loquat leaf, 2.5-3.5 parts stir-fried perilla seed, 3.5-4.5 parts cicada molting, 3.5-4.5 parts angelica root, 4.5-5.5 parts stir-fried burdock seed, and 3.5-4.5 parts schisandra fruit.

3. The traditional Chinese medicine oral gel for relieving wind-cold, clearing the lungs, stopping cough, and soothing the throat according to claim 2, characterized in that, The extract and / or volatile oil were prepared from the following components in parts by weight: 5 parts ephedra, 5 parts perilla leaf, 5 parts earthworm, 5 parts loquat leaf, 3 parts stir-fried perilla seed, 4 parts cicada molting, 4 parts angelica root, 5 parts stir-fried burdock seed, and 4 parts schisandra fruit.

4. The traditional Chinese medicine oral gel for dispelling wind and ventilating the lungs, relieving cough and soothing the throat according to claim 1, 2 or 3, characterized in that, The antibacterial agent is potassium sorbate; the sweetener is sucralose; the flavoring is Gannan orange flavoring. Based on the total amount of gelling agent (100%), the amount of xanthan gum added is 1.0%-2.5%, preferably 1.5%; the amount of potassium sorbate added is 0.1%-1.0%, preferably 0.15-0.25%, more preferably 0.2%; the amount of sucralose added is 0.1%-1.0%, preferably 0.2-0.3%, more preferably 0.2%; and the amount of Gannan orange flavoring added is 0.05%-0.5%, preferably 0.1-0.2%, more preferably 0.1%.

5. The preparation method of the traditional Chinese medicine oral gel for relieving wind-dampness, clearing the lungs, stopping cough, and soothing the throat as described in claim 1, characterized in that, Includes the following steps: (1) Preparation of volatile oil: Soak perilla leaves and angelica root in water for 0.5-1.5 hours, distill to extract volatile oil for 4-10 hours, and collect the obtained volatile oil; (2) Preparation of volatile oil inclusion complex: Hydroxypropyl-β-cyclodextrin and purified water were mixed evenly, and the volatile oil obtained in step (1) was slowly added. The mixture was then ground to prepare the volatile oil inclusion complex. (3) Preparation of extract: I) Ephedra and Schisandra chinensis were extracted three times by reflux with 80% ethanol, each extraction time being 1-2 hours. The extracts were filtered, the filtrates were combined, the ethanol was recovered, and the extract was concentrated to a thick paste with a relative density of 1.25-1.30 at 50℃ for later use. II) Earthworm, loquat leaf, stir-fried perilla seed, cicada molting, and stir-fried burdock seed are decocted three times with water, each time for 0.5-1 hour. The decoction is filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.09-1.11 at 50°C. Ethanol is added to make the alcohol content reach 65-75%. The paste is first refrigerated, filtered, and the ethanol is recovered. The paste is then concentrated to a thick paste with a relative density of 1.25-1.30 at 50°C. This paste is then combined with the thick paste obtained in step I), refrigerated again, and filtered to obtain the extract. (4) Gel preparation: a) Xanthan gum was added to purified water and swollen to obtain a matrix solution; b) Add the extract obtained in step (3), the volatile oil inclusion complex obtained in step (2), the antibacterial agent, the sweetener and the fragrance to the matrix solution, stir evenly, add purified water to make up the volume, vacuum, homogenize and degas to obtain the gel.

6. The method for preparing the traditional Chinese medicine oral gel for relieving wind-dampness, clearing the lungs, stopping cough, and soothing the throat according to claim 5, characterized in that, In step (1), the soaking time is 1 hour; the extraction time is 8 hours; in step (2), the weight ratio of hydroxypropyl-β-cyclodextrin to purified water is 1:0.2-1.5; the volume weight ratio of volatile oil to hydroxypropyl-β-cyclodextrin is 1:5-15 mL / g.

7. The method for preparing the traditional Chinese medicine oral gel for dispelling wind, clearing the lungs, relieving cough, and soothing the throat according to claim 5, characterized in that, In step I) of extract preparation, the extraction time is 1.5 hours each time; in step II) of extract preparation, the decoction time is 1 hour each time; ethanol is added until the alcohol content reaches 70%; the initial refrigeration time is 24 hours or more; the second refrigeration time is 48 hours or more.

8. The method for preparing the traditional Chinese medicine oral gel for dispelling wind, clearing the lungs, relieving cough and soothing the throat according to claim 5, characterized in that, Step b) of gel preparation When evacuating, control the vacuum level to 150 mbar-250 mbar; During homogenization, the control parameters are as follows: homogenization speed is 2000-2200 rpm; homogenization times are 2-4 times; homogenization time is 3-10 minutes.

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