Children cough and asthma treating granules as well as preparation method and application thereof

Abstract

The invention relates to an infantile cough and asthma treating granule as well as a preparation method and application thereof. The preparation method comprises the following steps: step 1, cleaning, drying, crushing and sieving ephedra, isatis root and honeysuckle to obtain traditional Chinese medicine powder; step 2, adding the traditional Chinese medicine powder in the step 1 into an ethanol solution, stirring, refrigerating and filtering to obtain medicine residues and an alcohol extract, recovering ethanol, and concentrating the alcohol extract into extract; 3, semen armeniacae amarae, gypsum, raw liquorice and trichosanthes kirilowii maxim are cleaned, dried, smashed and sieved, mixed with the medicine residues obtained in the step 2, added into deionized water, decocted and filtered, supernatant is taken, and the supernatant is concentrated into extract; and 4, respectively taking the extractum prepared in the step 2 and the extractum prepared in the step 3, adding 95 wt% ethanol, mixing, adding dextrin and powdered sugar, and carrying out vacuum low-temperature continuous drying granulation. According to the preparation method, the taste of the traditional Chinese medicine granules can be improved while the content of the effective components is increased, and the traditional Chinese medicine granules have very important clinical application value and commercial value.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to pediatric Kechuanling granules and a preparation method and use thereof. Background Art

[0002] Xiaoer Kechuanling Granule is a Chinese patent medicine preparation included in the fourth volume of the Ministry-issued Standard Chinese Medicine Formula Preparations, and the implementation standard is WS3-B-0688-91. Its functions and indications are to clear the lungs, clear away heat, relieve cough, eliminate phlegm, and relieve asthma. It is used for upper respiratory tract infections, tracheitis, pneumonia, cough, etc.

[0003] Xiaoer Kechuanling Granules are derived from the classic prescription Ma Xing Shi Gan Tang in the Treatise on Febrile Diseases by Zhang Zhongjing, a medical scientist in the late Eastern Han Dynasty. It is composed of seven herbs, including ephedra, bitter almonds, gypsum, raw licorice, isatis root, honeysuckle and trichosanthes. In the prescription, ephedra is bitter, sweet and warm, and can clear the lungs, relieve the exterior and relieve asthma; gypsum is pungent, sweet and very cold, and can clear the heat of the lungs and stomach to produce fluid; almonds are bitter, and can lower and benefit the lungs and relieve asthma and cough. When paired with ephedra, they can promote and consolidate, and when paired with gypsum, they can clear and purify; licorice is sweet and flat, and can clear away heat and detoxify, moisten the lungs and relieve cough, harmonize various herbs, protect stomach qi, prevent the severe cold of gypsum from damaging the stomach, and harmonize the cold and warm properties of ephedra and gypsum; trichosanthes can resolve phlegm and clear the bowels; honeysuckle and isatis root can disperse wind-heat, clear away heat and detoxify.

[0004] Among them, ephedra and honeysuckle are the main drugs of Xiaoer Kechuanling, and ephedrine hydrochloride and chlorogenic acid are important active ingredients in ephedra and honeysuckle, respectively. Among them, chlorogenic acid is unstable and prone to degradation, especially chlorogenic acid is greatly affected by high temperature, strong light and pH value. If the content of these two active ingredients can be effectively increased in the new preparation method, it is expected to provide better therapeutic effects. In addition, the taste of Chinese medicine granules is not easily accepted by children, which makes it difficult for children to take medicine. Therefore, if the new preparation method can improve the taste of the Chinese medicine granules while increasing the content of active ingredients, especially reducing bitterness, it is expected to greatly improve the compliance of children.

[0005] In view of this, developing a new preparation method that can overcome the above-mentioned defects and shortcomings in the prior art and is suitable for the commercial production of pediatric Kechuanling granules will have very important clinical application value and commercial value. Summary of the invention

[0006] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides a pediatric Kechuanling granule and a preparation method and use thereof. The preparation method of the present invention can improve the taste of the Chinese medicine granule while increasing the content of the effective ingredient, and has very important clinical application value and commercial value.

[0007] Specifically, the present invention is realized through the following technical solutions:

[0008] In a first aspect, the present invention provides a method for preparing pediatric Kechuanling granules, wherein the pediatric Kechuanling granules are prepared from the following raw materials: ephedra, bitter almonds, gypsum, raw licorice, isatis root, honeysuckle and trichosanthes, and the preparation method comprises the following steps:

[0009] Step 1: Wash, dry and crush ephedra, isatis root and honeysuckle through a 60-100 mesh sieve to obtain Chinese medicine powder;

[0010] Step 2: adding the Chinese medicine powder prepared in step 1 to a 70-80wt% ethanol solution, stirring, refrigerating for 12-48 hours, filtering to obtain the drug residue and the alcohol extract, recovering the ethanol and concentrating the alcohol extract to an extract;

[0011] Step 3: Wash, dry, and crush bitter almonds, gypsum, raw licorice, and Trichosanthes kirilowii through a 30-50 mesh sieve, mix with the drug residue obtained in step 2, add to deionized water, boil for 0.5-1.5 hours, filter, take the supernatant, and concentrate the supernatant to obtain an extract;

[0012] Step 4: Take the extracts prepared in step 2 and step 3 respectively, add 95wt% ethanol to mix, then add dextrin and powdered sugar, perform vacuum low-temperature continuous drying granulation, dry, crush, sieve, and package to obtain.

[0013] As an optional manner, in the above preparation method, the Xiaoer Kechuanling granules are made of the following raw materials, measured in parts by weight: 50-100 parts of ephedra, 350-400 parts of bitter almonds, 1100-1150 parts of gypsum, 350-400 parts of raw licorice, 700-800 parts of isatis root, 700-800 parts of honeysuckle and 350-400 parts of trichosanthes.

[0014] As an optional manner, in the above preparation method, the Xiaoer Kechuanling granules are made of the following raw materials, measured in parts by weight: 75 parts of ephedra, 375 parts of bitter almonds, 1125 parts of gypsum, 375 parts of raw licorice, 750 parts of isatis root, 750 parts of honeysuckle and 375 parts of trichosanthes.

[0015] As an optional manner, in the above preparation method, in step 1, ephedra, isatis root and honeysuckle are washed, dried, and crushed through an 80-mesh sieve to obtain traditional Chinese medicine powder.

[0016] As an optional manner, in the above preparation method, in step 2, the Chinese medicine powder prepared in step 1 is added to a 75wt% ethanol solution at a solid-liquid ratio of 1:2, stirred, refrigerated for 24 hours, filtered to obtain the residue and alcohol extract, recovered ethanol and concentrated the alcohol extract to an extract.

[0017] As an optional manner, in the above preparation method, in step 3, the bitter almonds, gypsum, raw licorice and Trichosanthes kirilowii are washed, dried, crushed and passed through a 40-mesh sieve, mixed with the medicinal residues obtained in step 2, and then added to deionized water at a solid-liquid ratio of 1:3, decocted for 1 hour, filtered, the supernatant was taken, and the supernatant was concentrated to an extract.

[0018] As an optional manner, in the above preparation method, in step 4, the weight ratio is extract: dextrin: powdered sugar = (5-20): (1-10): (1-10), and in weight percentage, the amount of 95wt% ethanol added is 5%-10% of the weight of the extract.

[0019] Preferably, in the above preparation method, in step 4, the weight ratio of extract: dextrin: powdered sugar is 10:3:2.

[0020] Preferably, in the above preparation method, in step 4, the amount of 95wt% ethanol added is 8% of the weight of the extract, in terms of weight percentage.

[0021] Preferably, in the above preparation method, in step 4, the particles are sieved with a 20-mesh sieve after pulverization, and the moisture content of the particles is controlled at 3-5% by weight.

[0022] As an optional manner, in the above preparation method, in step 2, the alcohol extract is concentrated to an extract with a relative density of 1.20-1.24 at 60°C; in step 3, the supernatant is concentrated to an extract with a relative density of 1.22-1.28 at 60°C.

[0023] In a second aspect, the present invention provides pediatric Kechuanling granules prepared by the preparation method described in the first aspect, wherein the contents of the active ingredients ephedrine hydrochloride and chlorogenic acid in the pediatric Kechuanling granules are increased and the taste is improved.

[0024] In the third aspect, the present invention provides the use of the Xiaoer Kechuanling Granules described in the second aspect in the preparation of medicines for treating upper respiratory tract infections, tracheitis, pneumonia or coughs, wherein the Xiaoer Kechuanling Granules have the effects of dispersing lung, clearing heat, relieving cough, removing phlegm and relieving asthma.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) The preparation method of the present invention can improve the taste of the Chinese medicine granules while increasing the content of effective ingredients (especially ephedrine hydrochloride and chlorogenic acid), and has very important clinical application value and commercial value.

[0027] (2) The results of pharmacological experiments show that the Kechuanling granules prepared by the method of the present invention have higher therapeutic effects than the Kechuanling granules commonly available on the market.

[0028] (3) In the preparation method of the present invention, a pretreatment process of the paste before spray drying is added, in which the extracted paste is added to 8% of 95wt% ethanol for mixing. This process is more conducive to the standardized execution of the process, improves the spraying efficiency, and improves the product quality of the granules. DETAILED DESCRIPTION

[0029] The present invention will be further described with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0030] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0031] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0032] Preparation Example:

[0033] Embodiment 1:

[0034] A method for preparing pediatric Kechuanling granules, wherein the pediatric Kechuanling granules are prepared from the following raw materials: 75 parts of ephedra, 375 parts of bitter almonds, 1125 parts of gypsum, 375 parts of raw licorice, 750 parts of isatis root, 750 parts of honeysuckle and 375 parts of trichosanthes, and the preparation method comprises the following steps:

[0035] Step 1: Wash, dry, and crush ephedra, isatis root, and honeysuckle through an 80-mesh sieve to obtain Chinese medicine powder;

[0036] Step 2: adding the Chinese medicine powder prepared in step 1 to a 75wt% ethanol solution at a material-liquid ratio of 1:2, stirring, refrigerating for 24 hours, filtering to obtain the drug residue and the alcohol extract, recovering the ethanol and concentrating the alcohol extract to an extract having a relative density of 1.20-1.24 at 60°C;

[0037] Step 3: Wash, dry, and crush bitter almonds, gypsum, raw licorice, and Trichosanthes kirilowii through a 40-mesh sieve, mix with the medicinal residue obtained in step 2, add into deionized water at a solid-liquid ratio of 1:3, boil for 1 hour, filter, take the supernatant, and concentrate the supernatant to an extract with a relative density of 1.22-1.28 at 60°C;

[0038] Step 4: Take the extracts prepared in step 2 and step 3 respectively, add 95wt% ethanol to mix, then add dextrin and powdered sugar, carry out vacuum low-temperature continuous drying granulation, dry, crush, sieve, and package to obtain, in weight ratio, extract: dextrin: powdered sugar = 10:3:2, in weight percentage, the amount of 95wt% ethanol added is 8% of the weight of the extract, after crushing, use a 20-mesh sieve to sieve, in weight percentage, the moisture content of the particles is controlled at 4%.

[0039] Comparative Example 1:

[0040] A method for preparing pediatric Kechuanling granules, wherein the pediatric Kechuanling granules are prepared from the following raw materials: 75 parts of ephedra, 375 parts of bitter almonds, 1125 parts of gypsum, 375 parts of raw licorice, 750 parts of isatis root, 750 parts of honeysuckle and 375 parts of trichosanthes, and the preparation method comprises the following steps:

[0041] Step 1: Add 10 times the amount of water to ephedra, bitter almonds, gypsum, and raw licorice, boil for 1 hour, and filter;

[0042] Step 2: Add 12 times the amount of water to the residue, Radix Isatidis, Flos Lonicerae and Fructus Trichosanthis, and boil for 1 hour, then filter;

[0043] Step 3: Combine the filtrates from step 1 and step 2, mix them evenly, let them stand for more than 24 hours, take the supernatant, concentrate the supernatant to a relative density of 1.22-1.28 (60°C) fluid extract, add 1 times the amount of 95% ethanol, stir them evenly, refrigerate for more than 24 hours, filter the supernatant, recover the ethanol and concentrate it to a relative density of 1.20-1.24 (60°C) extract;

[0044] Step 4: add dextrin and powdered sugar to the extract (relative density of 1.20) prepared in step 3 according to the ratio of extract / (dextrin+powdered sugar, wherein dextrin:powdered sugar (1:1)) (10:5), mix well, and perform vacuum low-temperature continuous drying to prepare granules. After crushing, sieve with a 20-mesh sieve. The moisture content of the granules is controlled at 4% by weight.

[0045] Comparative Example 2:

[0046] A method for preparing pediatric Kechuanling granules, wherein the pediatric Kechuanling granules are prepared from the following raw materials: 75 parts of ephedra, 375 parts of bitter almonds, 1125 parts of gypsum, 375 parts of raw licorice, 750 parts of isatis root, 750 parts of honeysuckle and 375 parts of trichosanthes, and the preparation method comprises the following steps:

[0047] Step 1: Add 10 times the amount of water to gypsum, bitter almonds, raw licorice, isatis root, and trichosanthes, boil for 1 hour, and filter;

[0048] Step 2: Add 10 times the amount of water to the residue, ephedra and honeysuckle, and boil for 1 hour, then filter;

[0049] Step 3: Combine the filtrates from step 1 and step 2, mix them evenly, let them stand for more than 24 hours, take the supernatant, concentrate the supernatant to a relative density of 1.24-1.26 (60°C) fluid extract, add 1 times the amount of ethanol, stir well, refrigerate for 24-48 hours, filter the supernatant, recover the ethanol and concentrate it to a relative density of 1.29-1.31 (60°C) extract;

[0050] Step 4: Add dextrin and powdered sugar (dextrin / powdered sugar is 1:4) to the extract prepared in step 3 according to the ratio of extract / auxiliary materials (1:2), mix evenly, wet granulate, dry, granulate, mix evenly, and package.

[0051] Effect verification example:

[0052] Effect Example 1: Preparation properties of the Xiaoer Kechuanling granules prepared by the method of the present invention

[0053] The properties of various preparations of the Kechuanling granules prepared by the method of the present invention are shown in Table 1. The results show that the Kechuanling granules (Example 1) prepared by the method of the present invention are superior to the existing methods in terms of properties, particle size, solubility and main active ingredient content, especially in terms of the main active ingredient content.

[0054] Table 1:

[0055]

[0056]

[0057] Example 2: Bitterness analysis experiment of Xiaoer Kechuanling granules prepared by the method of the present invention

[0058] The Kechuanling granules for children prepared by the methods of Example 1, Comparative Example 1 and Comparative Example 2 were added to water at an addition amount of 0.5 g / mL, and the bitterness level was analyzed by electronic tongue. The experimental results are shown in Table 2 below. The results show that the bitterness of the Kechuanling granules for children (Example 1) prepared by the method of the present invention is significantly lower than that of the existing method, the bitterness is reduced, and the taste of the granules is significantly improved, which can greatly improve the medication compliance of children.

[0059] Table 2:

[0060] Test items Example 1 Comparative Example 1 Comparative Example 2 Bitterness level 2.9 5.1 6.3

[0061] Example 3: Pharmacodynamics study of the Xiaoer Kechuanling granules prepared by the method of the present invention 3.1 Antitussive Experiment:

[0062] Male ICR mice (purchased from Liaoning Changsheng Biotechnology Co., Ltd.), 18-22g, were randomly divided into a blank group, a model group, an example 1 group, a comparative example 1 group and a comparative example 2 group after one week of adaptive feeding, 8 mice in each group. The blank group and the model group were intragastrically administered with normal saline, and the example 1 group, the comparative example 1 group and the comparative example 2 group were intragastrically administered with the granules prepared in the above preparation example, 5.0g / kg. The administration volume of each group was 0.2mL / 10g.

[0063] The drug was administered once a day for 3 consecutive days. One hour after the last administration, a cotton ball was placed in an inverted 500mL beaker, and 300μL of 25% ammonia water was injected. After saturation for 1 minute, the mouse was quickly placed in the beaker, taken out after 45 seconds, and placed in another inverted clean 500mL beaker. The typical coughing action (abdominal muscle contraction, wide mouth opening, and coughing sound) was observed, and the cough latency (the time from taking out to the first cough) and the number of coughs within 5 minutes were recorded.

[0064] SPSS23.0 statistical software was used for data analysis, and the measurement data were expressed as mean±standard deviation (mean±SD). One-way ANOVA was used for comparison among multiple groups. LSD test was used for equal variance test, and Euskal-Walli SH method was used for non-parametric test for unequal variance. P<0.05 was considered statistically significant.

[0065] The experimental results are shown in Table 3. The experimental results show that compared with the comparative example 2 group (granules prepared according to the ministerial standard WS3-B-0688-91), after administration of the Xiaoer Kechuanling granules (Example 1 group) prepared by the method of the present invention, the number of coughs of the experimental mice was significantly reduced, the cough latency was significantly prolonged, and it was significantly better than the comparative example 1 group.

[0066] Table 3:

[0067] Group Number of coughs (times) Cough incubation period(s) Blank Group -- 300 Model Group 23.18±2.31 17.35±2.07 Example 1 Group <![CDATA[4.93±0.85 ** ]]> <![CDATA[63.29±3.82 ** ]]> Comparative Example 1 <![CDATA[7.15±2.26 * ]]> <![CDATA[48.46±4.93 * ]]> Comparative Example 2 12.71±2.94 31.43±2.81

[0068] Note: Compared with control group 2, *p<0.05, **p<0.01.

[0069] 3.2 Antiasthmatic Experiment:

[0070] Male ICR mice (purchased from Liaoning Changsheng Biotechnology Co., Ltd.), 18-22g, were randomly divided into a model group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group after one week of adaptive feeding, 8 mice in each group. The model group was given normal saline by gavage, and the Example 1 group, Comparative Example 1 group and Comparative Example 2 group were given 5.0g / kg of the granules prepared in the above preparation example. The administration volume of each group was 0.2mL / 10g.

[0071] The drug was administered once a day for 3 consecutive days. 0.5 h after the last administration, the mice were placed in a YLS-8A multifunctional cough and asthma induction instrument (Jiangsu Seons Biotechnology Co., Ltd.) and sprayed with 5% histamine phosphate solution for 30 s. The latency period of asthma induction in the mice was then recorded and observed within 6 min, that is, the time from the spraying of the drug solution to the first convulsion of the mice.

[0072] The experimental results are shown in Table 4. The experimental results show that compared with the comparative example 2 group (granules prepared according to the ministerial standard WS3-B-0688-91), after administration of the Xiaoer Kechuanling granules (Example 1 group) prepared by the method of the present invention, the latency of asthma in experimental mice was significantly prolonged, and was significantly better than the comparative example 1 group.

[0073] Table 4:

[0074] Group Latent period of asthma induction (s) Model Group 78.24±21.36 Example 1 Group <![CDATA[215.67±33.59 ** ]]> Comparative Example 1 <![CDATA[188.21±27.48 * ]]> Comparative Example 2 156.13±24.97

[0075] Note: Compared with control group 2, *p<0.05, **p<0.01.

[0076] In summary, the preparation method of the present invention can improve the taste of the Chinese medicine granules while increasing the content of effective ingredients (especially ephedrine hydrochloride and chlorogenic acid), and has very important clinical application value and commercial value. The pediatric Kechuanling granules prepared by the method of the present invention have higher therapeutic effects than ordinary commercially available pediatric Kechuanling granules. In the preparation method of the present invention, a pretreatment process of the paste before spray drying is also added, and the extraction paste is added to 8% of 95wt% ethanol for mixing. The use of this process is more conducive to the standardized execution of the process, improves the spray efficiency, and improves the product quality of the granules.

[0077] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing pediatric Kechuanling granules, characterized in that: The Xiaoer Kechuanling granules are prepared from the following raw materials: ephedra, bitter almond, gypsum, raw licorice, isatis root, honeysuckle and trichosanthes, and the preparation method comprises the following steps: Step 1: Wash, dry and crush ephedra, isatis root and honeysuckle through a 60-100 mesh sieve to obtain Chinese medicine powder; Step 2: adding the Chinese medicine powder prepared in step 1 to a 70-80wt% ethanol solution, stirring, refrigerating for 12-48 hours, filtering to obtain the drug residue and the alcohol extract, recovering the ethanol and concentrating the alcohol extract to an extract; Step 3: Wash, dry, and crush bitter almonds, gypsum, raw licorice, and Trichosanthes kirilowii through a 30-50 mesh sieve, mix with the drug residue obtained in step 2, add to deionized water, boil for 0.5-1.5 hours, filter, take the supernatant, and concentrate the supernatant to obtain an extract; Step 4: Take the extracts prepared in step 2 and step 3 respectively, add 95wt% ethanol to mix, then add dextrin and powdered sugar, perform vacuum low-temperature continuous drying granulation, dry, crush, sieve, and package to obtain.

2. The preparation method according to claim 1, characterized in that: The Xiaoer Kechuanling granules are prepared from the following raw materials in parts by weight: 50-100 parts of ephedra, 350-400 parts of bitter almonds, 1100-1150 parts of gypsum, 350-400 parts of raw licorice, 700-800 parts of isatis root, 700-800 parts of honeysuckle and 350-400 parts of trichosanthes.

3. The preparation method according to claim 1, characterized in that: The Xiaoer Kechuanling granules are prepared from the following raw materials in parts by weight: 75 parts of ephedra, 375 parts of bitter almonds, 1125 parts of gypsum, 375 parts of raw licorice, 750 parts of isatis root, 750 parts of honeysuckle and 375 parts of trichosanthes.

4. The preparation method according to claim 1, characterized in that: In step 1, ephedra, isatis root and honeysuckle are washed, dried, and crushed through an 80-mesh sieve to obtain traditional Chinese medicine powder.

5. The preparation method according to claim 1, characterized in that: In step 2, the Chinese medicine powder prepared in step 1 is added to a 75wt% ethanol solution at a solid-liquid ratio of 1:2, stirred, refrigerated for 24 hours, filtered to obtain the drug residue and the alcohol extract, recovered the ethanol and concentrated the alcohol extract to an extract.

6. The preparation method according to claim 1, characterized in that: In step 3, the bitter almonds, gypsum, raw licorice and Trichosanthes kirilowii are washed, dried, crushed and passed through a 40-mesh sieve, mixed with the medicinal residues obtained in step 2, added into deionized water at a solid-liquid ratio of 1:3, boiled for 1 hour, filtered, the supernatant was taken, and the supernatant was concentrated to an extract.

7. The preparation method according to claim 1, characterized in that: In step 4, in terms of weight ratio, extract: dextrin: powdered sugar = (5-20): (1-10): (1-10), and in terms of weight percentage, the amount of 95wt% ethanol added is 5%-10% of the weight of the extract.

8. The preparation method according to claim 5 or claim 6, characterized in that: In step 2, the alcohol extract is concentrated to an extract having a relative density of 1.20-1.24 at 60°C; in step 3, the supernatant is concentrated to an extract having a relative density of 1.22-1.28 at 60°C.

9. The Xiaoer Kechuanling granules prepared by the preparation method according to any one of claims 1 to 8, characterized in that: The Xiaoer Kechuanling granules have increased contents of the effective ingredients ephedrine hydrochloride and chlorogenic acid and have an improved taste.

10. Use of the Xiaoer Kechuanling granules according to claim 9 in the preparation of a medicine for treating upper respiratory tract infection, tracheitis, pneumonia or cough, characterized in that: The Xiaoer Kechuanling granules have the effects of promoting lung function, clearing away heat, relieving cough, removing phlegm and relieving asthma.

Images