Novel compound traditional Chinese medicine asthma-relieving aerosol and preparation method thereof

Abstract

The invention discloses a novel compound traditional Chinese medicine asthma-relieving aerosol which is prepared from the following raw materials in parts by weight: 10-60 parts of agastache rugosus, 10-60 parts of pericarpium citri reticulatae, 10-60 parts of mangnolia officinalis and 10-60 parts of perilla leaves. The invention further discloses a preparation method of the novel compound traditional Chinese medicine asthma-relieving aerosol. The invention provides an efficient and safe traditional Chinese medicine asthma-relieving aerosol capable of treating acute attack of asthma and a preparation method thereof, the aerosol is convenient to dose, can be inhaled through atomization, is convenient to use, has a unique treatment effect, can effectively prevent and treat asthma patients after being continuously used twice a day for 5-7 days, treats both symptoms and root causes, and is short in treatment period, quick in effect taking, reliable in effect and free of toxic and side effects. The traditional Chinese medicine composition has the effects of spasmolysis, anti-inflammation, anti-allergic reaction and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of anti - asthma medicaments, and particularly to a novel compound traditional Chinese medicine anti - asthma aerosol and a preparation method thereof. Background Art

[0002] Bronchial asthma is a common and frequently - occurring disease, which poses a great threat to human health and has become a relatively serious health problem. Bronchial asthma is extremely harmful, with a high fatality and disability rate.

[0003] Currently, commonly used drugs for treating asthma in clinical practice, such as glucocorticoids and leukotriene receptor antagonists, can quickly control airway inflammation. However, there are still some drawbacks, such as recurrence after drug withdrawal and systemic or local adverse reactions caused by long - term medication. These will seriously affect the quality of life of patients and bring a huge economic burden to families and society. Therefore, exploring new drugs and conducting in - depth research on bronchial asthma has profound social significance and potential economic value. Summary of the Invention

[0004] Aiming at the technical problems existing in the background art, the purpose of the present invention is to provide a novel compound traditional Chinese medicine anti - asthma aerosol with reliable efficacy and few side effects and a preparation method thereof.

[0005] In order to achieve the above - mentioned purpose, the technical scheme adopted by the present invention is as follows:

[0006] A novel compound traditional Chinese medicine anti - asthma aerosol, which is prepared from the following raw materials in parts by weight: 10 - 60 parts of Herba Pogostemonis, 10 - 60 parts of Pericarpium Citri Reticulatae Viride, 10 - 60 parts of Cortex Magnoliae Officinalis, and 10 - 60 parts of Folium Perillae.

[0007] Further, the weight ratio of Herba Pogostemonis, Pericarpium Citri Reticulatae Viride, Cortex Magnoliae Officinalis, and Folium Perillae is 1:1:1:1.

[0008] The present invention also discloses a preparation method of a novel compound traditional Chinese medicine anti - asthma aerosol, which comprises the following steps:

[0009] S1. Weigh Herba Pogostemonis, Pericarpium Citri Reticulatae Viride, Cortex Magnoliae Officinalis, and Folium Perillae according to the parts by weight, totaling 200 parts, add 8 times the weight of water and soak for 0.3 - 1 h to obtain a mixed liquid of soaked medicinal materials.

[0010] S2. Distill the mixed liquid of soaked medicinal materials in step S1, collect 100 ml of aromatic water, store it separately, and let it cool for later use.

[0011] S3. Reflux - extract the distilled mixed liquid of soaked medicinal materials for 0.8 - 1.5 h and then filter, and concentrate the medicinal liquid to 200 ml.

[0012] S4. After allowing the concentrated medicinal liquid to cool, add an organic solvent so that the content of the organic solvent in the medicinal liquid reaches 55% - 70%. Let it stand for 18 - 30 h and then filter. Recover the organic solvent to obtain an extract.

[0013] S5. Combine the extract with aromatic water. The ratio of the extract to the aromatic water is 1:1. Add water to make up the volume to 200 ml. Add 1% non-ionic surfactant and 0.05% preservative, mix well and fill into containers, then press in propellants or compressed air to obtain the novel compound traditional Chinese medicine anti-asthma aerosol.

[0014] Further, in step S2, decoct the medicinal material soaking mixture for 0.8 - 1.2 h. After filtration, concentrate the decoction to 200 ml. Let it cool and add absolute ethanol so that the alcohol content in the concentrated solution reaches 65% - 70%. Use the steam distillation method to collect 100 ml of aromatic water.

[0015] Preferably, in step S4, the organic solvent is absolute ethanol.

[0016] Preferably, in step S5, the non-ionic surfactant is Tween 80.

[0017] Preferably, in step S5, the preservative is ethyl paraben.

[0018] Preferably, in step S5, the propellant is hydrofluoroalkane.

[0019] The present invention has the following beneficial effects: It provides a highly effective and safe traditional Chinese medicine anti-asthma aerosol capable of treating acute asthma attacks and its preparation method. This aerosol is convenient for administration, can be inhaled by atomization, is easy to use, has a unique therapeutic effect, can effectively prevent and treat asthma patients when used twice a day for 5 - 7 days, treats both the symptoms and root causes, has a short treatment cycle, rapid onset, reliable effect, and small side effects, and has effects such as spasmolysis, anti-inflammation, and anti-allergic reaction, and has good economic prospects and social benefits. Applying the aerosol of the present invention to animal experiments and clinical observations has an anti-asthma effect on animals, can effectively reduce the airway hyperresponsiveness of asthmatic model guinea pigs, reduce the number of blood eosinophils EOS, and at the same time improve lung function. Specific Embodiments

[0020] The following further describes the present invention in combination with specific embodiments.

[0021] Traditional Chinese medicine not only has rich clinical experience and definite curative effects in the prevention and treatment of asthma, can adjust the dynamic balance of the body through multiple channels, multiple links and multiple targets, and has fewer disadvantages, so it has increasingly attracted the attention of scholars at home and abroad. In order to explore new fields of traditional Chinese medicine in the treatment of acute asthma, the research group found through previous research that Huoxiang Zhengqi San has the effect of blocking mast cell degranulation, suggesting its effects such as anti-Type I allergic reaction, etc. On the basis of the effective oral treatment of asthma with it, ultrasonic aerosol inhalation was used to treat acute asthma attacks and achieved good results. Therefore, the research status of treating asthma with Huoxiang Zhengqi Shui, a classic representative formula for aromatizing dampness turbidity, was summarized, the formula design was explored, and herbs such as Herba Pogostemonis, Pericarpium Citri Reticulatae, Cortex Magnoliae Officinalis, and Folium Perillae were selected, and the effective components were extracted by methods such as steam distillation, and the self-made pure traditional Chinese medicine aerosol was named "Traditional Chinese Medicine Pingchuan Aerosol" by aerosol administration method.

[0022] The research group previously applied the Traditional Chinese Medicine Pingchuan Aerosol to animal experiments and clinical observations and found that it has an anti-asthmatic effect, can effectively reduce the airway hyperresponsiveness of guinea pigs in the asthma model, reduce the number of blood eosinophils (EOS), and at the same time improve lung function. To sum up, the research group of this project has confirmed that the formula of the Traditional Chinese Medicine Pingchuan Aerosol guided by the method of aromatizing dampness turbidity conforms to the basic treatment method of "aromatizing dampness turbidity" in traditional Chinese medicine theory and has definite curative effects in clinical application for the treatment of asthma.

[0023] The present invention discloses a novel compound traditional Chinese medicine Pingchuan Aerosol, which is made from the following raw materials in parts by weight: 10-60 parts of Herba Pogostemonis, 10-60 parts of Pericarpium Citri Reticulatae, 10-60 parts of Cortex Magnoliae Officinalis, 10-60 parts of Folium Perillae. Specifically, the weight ratio of Herba Pogostemonis, Pericarpium Citri Reticulatae, Cortex Magnoliae Officinalis, and Folium Perillae is 1:1:1:1.

[0024] The present invention also discloses a preparation method of a novel compound traditional Chinese medicine Pingchuan Aerosol, which comprises the following steps:

[0025] The first step: Weigh Herba Pogostemonis, Pericarpium Citri Reticulatae, Cortex Magnoliae Officinalis, and Folium Perillae according to the parts by weight, totaling 200 parts. After cleaning and cutting, add 8 times the weight of water and soak for 0.5 h to obtain a mixed liquid of soaked medicinal materials.

[0026] The second step: Decoct the mixed liquid of soaked medicinal materials for 1 h. After filtration, concentrate the decoction to 200 ml, let it cool and add absolute ethanol to make the alcohol content in the concentrated liquid reach 70%. Collect 100 ml of aromatic water by steam distillation method, store it separately, and let it cool for later use.

[0027] The third step: After reflux extraction of the mixed liquid of soaked medicinal materials after distillation for 1 h, filter it, and concentrate the medicinal liquid to 200 ml.

[0028] The fourth step: After the concentrated medicinal liquid is cooled, add absolute ethanol to make the ethanol content in the medicinal liquid reach 60%. Let it stand for 24 h and then filter it, recover the ethanol, and obtain an extract.

[0029] The fifth step is to combine the extract with aromatic water in a ratio of 1:1, add water to make the volume to 200 ml, add 1% Tween 80 and 0.05% ethyl paraben, mix well and fill, press into propellant or compressed air, the propellant is hydrofluoroalkane, and prepare a new type of compound Chinese medicine antiasthmatic aerosol (1g crude drug / ml) and put it in a spray bottle.

[0030] The novel compound Chinese medicine antiasthmatic aerosol prepared by the present invention was experimented.

[0031] Experiment 1: The novel compound Chinese medicine antiasthmatic aerosol prepared by the present invention was subjected to an animal antiasthmatic experiment.

[0032] First, prepare other aerosols for the control group:

[0033] (1) Shuchuanling aerosol

[0034] Take 48 mg of salbutamol, grind it into powder, add distilled water to 48 ml to fully dissolve it and filter it. Collect the filtrate and add distilled water to 48 ml. After fully stirring, put 40 ml into an aerosol can for later use.

[0035] (2) Atropine sulfate aerosol

[0036] Take 60 mg of atropine sulfate, grind it into powder, add distilled water to 60 ml, fully dissolve it and filter it. Collect the filtrate and add distilled water to 60 ml. After fully stirring, put 40 ml into an aerosol can for later use.

[0037] (3) Physiological saline aerosol

[0038] Take 40 ml of 0.9% sodium chloride injection and put it directly into the aerosol can for later use.

[0039] The drug-induced asthma method (spray-induced asthma method) is used. Guinea pigs (weighing less than 250g) are placed in a sealed glass bell jar and 1ml of a mixture of 2% histamine phosphate and 0.4% acetylcholine chloride (2:1) is sprayed with a quantitative nebulizer. After the spray stops, the guinea pigs will experience shortness of breath, wheezing, or even suffocation, resulting in convulsions or falls, etc., which means that the animal guinea pig asthma model is successfully established. The time from the start of spraying to convulsions and falls is called the asthma induction latency. The asthma induction experiment is carried out the day before the experiment. If the asthma induction latency is greater than 120s, it is insensitive and is eliminated.

[0040] Qualified guinea pigs were randomly divided into Pingchuan aerosol group, Shuchuling group, Atropine sulfate group and saline group, with 10 animals in each group. The weight distribution of animals among the groups was balanced (P>0.05), which was comparable.

[0041] The above 4 groups of animals were each administered once (2 sprays of the corresponding spray into the mouth). After 10 min, they were placed in a sealed glass bell jar, and 1 mL of a mixed solution of 2% histamine phosphate and 0.4% acetylcholine chloride (2:1) was sprayed in using a quantitative nebulizer under the same conditions as during pre-selection. The asthma induction latency and the number of animals that fell were observed and recorded.

[0042] All measurement data are expressed as mean ± standard deviation and were analyzed using t-tests and exact probability calculations. The experimental results are shown in Table 1.

[0043]

[0044] Table 1

[0045] The above experimental results show that the novel compound traditional Chinese medicine pingchuan aerosol, salbutamol, and atropine sulfate all have obvious preventive effects on asthma induced by a mixed solution of acetylcholine and histamine in guinea pigs. The latency of convulsions and falls in the guinea pigs in each drug-administered group was significantly longer than that in the normal saline group (P < 0.05 or P < 0.01 or P < 0.001); when comparing the latency between the salbutamol group and the pingchuan aerosol group, the salbutamol group was significantly superior to the pingchuan aerosol group (P < 0.01); when comparing the pingchuan aerosol group with the atropine group, there was no significant difference in latency (P > 0.05). When comparing the number of animals that fell among the groups, only the difference between the salbutamol group and the control group was significant (P < 0.001), and there was no significant difference among the other groups. Pharmacological studies have confirmed that the drugs in the pingchuan aerosol have effects such as spasmolysis, anti-inflammation, and anti-allergic reactions, and their effects are similar to those of western medicine cholinergic blockers and hormones. It is expected to become a highly effective and safe traditional Chinese medicine compound aerosol for the treatment of acute asthma attacks.

[0046] Experiment 2: The novel compound traditional Chinese medicine pingchuan aerosol prepared in the present invention was subjected to a clinical experiment.

[0047] According to the criteria specified by the National Asthma Conference in 1997, 60 outpatients and inpatients with mild to moderate asthma were screened. None of the patients had contraindications to the use of theophylline or a history of allergy to β2-receptor agonists.

[0048] The patients were randomly divided into a treatment group and a control group. There were 30 patients in the treatment group, including 18 males and 12 females, with an average age of (51.2 ± 12.8) years and an average disease course of (7.5 ± 3.1) years. Among them, 12 had mild disease and 18 had moderate disease, including 13 with cold asthma and 17 with heat asthma. There were 30 patients in the control group, including 14 males and 16 females, with an average age of (48.6 ± 13.4) years and an average disease course of (7.5 ± 2.1) years. Among them, 14 had mild disease and 16 had moderate disease, including 14 with cold asthma and 16 with heat asthma. There were no significant differences in general data such as gender, age, disease course, disease condition, and syndrome type among the groups (P > 0.05), and they were comparable.

[0049] Treatment group: Inhaled 5 ml of the new compound traditional Chinese medicine Pingchuan aerosol once a day, and inhaled salbutamol aerosol as needed; the course of treatment was 10 days. In the control group of 30 cases, 0.2 g of doxofylline was intravenously dripped with 100 ml of normal saline twice a day, and salbutamol aerosol was inhaled as needed; additionally, 5 ml of normal saline was inhaled by atomization once a day, and the course of treatment was 10 days.

[0050] Observation content: Changes in main symptoms and signs before and after treatment and determination of the following laboratory indicators: lung function, direct count of eosinophils in peripheral blood (EOS).

[0051] Efficacy evaluation criteria: According to the asthma efficacy evaluation criteria of the Respiratory Disease Branch of the Chinese Medical Association in 1997: Clinical control: Asthma symptoms are completely relieved, and even if there are occasional mild attacks, they can be relieved without medication, and the increase in PEV1 or (PEF) > 35%; Marked effect: Asthma attacks are significantly reduced compared with before treatment, the increase in PEV1 or (PEF) after treatment is 25% - 35%, or FEV1 or (PEF) after treatment reaches 60% - 79% of the predicted value, and the diurnal variation rate of PEF < 20%, and glucocorticoids or bronchodilators are still needed; Improvement: Asthma symptoms are somewhat alleviated, the increase in PEV1 or (PEF) is 15% - 24%, and glucocorticoids or bronchodilators are still needed; Ineffective: Clinical symptoms and PEF show no improvement or even worsen.

[0052] Statistical method: Analyzed using SPSS 10.0 statistical software, all measurement data were expressed as the mean and t-test was used. Chi-square test was used for count data, and Ridit test was used for ranked data. P < 0.05 was considered statistically significant.

[0053] (1) The comparison results of the control and marked effect rates before and after treatment are shown in Table 2

[0054] Group Number of cases Control Marked effect Improvement No effect Control and marked effect rate (%) Control group 30 3 8 12 7 36.67 Treatment group 30 7 13 6 4 66.67

[0055] Table 2

[0056] The following conclusions can be drawn from Table 2: There was a statistically significant difference between the treatment group and the control group (P < 0.05), and the curative effect was stable. After x 2 test, the comparison of the control and marked effect rates between the two groups was statistically significant (P < 0.05).

[0057] (2) The changes in lung function before and after treatment are shown in Table 3

[0058]

[0059] The following conclusions can be drawn from Table 3: After treatment, the FEV1 and PEF of the treatment group were higher than those of the control group, and the difference was statistically significant (P < 0.05). When comparing the FEV1 and PEF before and after treatment between the two groups, the treatment group was higher than the control group, and the difference was statistically significant (P < 0.01).

[0060] (3) The changes in peripheral eosinophils before and after treatment are shown in Table 4

[0061] Group Number of cases Before treatment After treatment Control group 30 0.244±0.049 0.156±0.051 Treatment group 30 0.249±0.059 0.126±0.045

[0062] The following conclusions can be drawn from Table 4: When comparing the eosinophil count (EOS) before and after treatment between the two groups, the treatment group was lower than the control group, and the difference was highly statistically significant (P < 0.01). When comparing before and after treatment between the two groups, the treatment group was lower than the control group, and the difference was statistically significant (P < 0.05).

[0063] (4) The relationship between the TCM syndrome types and the curative effect in the treatment group is shown in Table 5

[0064] Syndrome type Number of cases Control Marked effect Improvement No effect Cold asthma group 13 3 6 2 2 Heat asthma group 17 4 7 4 2

[0065] The following conclusions can be drawn from Table 5: After statistical processing (Ridit test), in the analysis of the syndrome types of the treatment group, there was no significant difference between the cold asthma group and the heat asthma group (P > 0.05).

[0066] Traditional Chinese medicine theory believes that the pathogenesis of asthma lies in "having phlegm retained internally and being triggered by external factors". The main inducing factors of asthma are external pathogens, diet, emotions, fatigue, etc., among which climate change is the main one. The key to the attack of asthma syndrome is that the phlegm retained internally is triggered by one or several inducing factors, resulting in the rise of phlegm with qi, the obstruction of qi by phlegm, mutual attack and obstruction of the airway, the narrowing of the lung tubes, the adverse rise and fall of lung qi, resulting in dyspnea, gasping, and the main manifestation being excess pathogen. Therefore, in the acute attack stage of this disease, TCM treats it by attacking the pathogen and relieving the symptoms. Just as Zhu Danxi summarized the treatment method of asthma in the book "Danxi's Heart Method" as "strengthening the healthy qi mainly before the attack and attacking the pathogen urgently during the attack", this theory has been followed by later physicians. The most common syndrome types in the acute attack of asthma syndrome are cold asthma and heat asthma.

[0067] The new compound traditional Chinese medicine Pingchuan aerosol is a new formula created on the basis of the pathological analysis of bronchial asthma, the efficacy and pharmacological effects of the classical prescriptions for treating bronchial asthma, and the pharmacological effects of the medicine. The comparison between the classical prescription and the new formula is carried out, which not only fully targets the pathology of asthma but also contains the main medicine of the classical prescription that can fully exert its pharmacological effects. It has been confirmed by previous animal experiments that the new compound traditional Chinese medicine Pingchuan aerosol has obvious spasmolytic and anti-asthmatic effects.

[0068] The results of this study showed that the curative effect of the treatment group treated with the new compound traditional Chinese medicine Pingchuan aerosol combined with conventional western medicine treatment was significantly better than that of the control group treated with western medicine alone. After treatment, both PEF and FEV1 in the two groups increased significantly. Compared with the control group, the increase in the treatment group was significant, indicating a significant improvement in lung function. After treatment, EOS in both groups decreased significantly. After comparison between the two groups after treatment, the decrease in the treatment group was obvious, indicating that the treatment group was more effective in reducing EOS. From the overall results of the clinical study, the clinical efficacy and laboratory test indexes of the treatment group with the new compound traditional Chinese medicine Pingchuan aerosol were better than those of the western medicine control group alone, indicating that the new compound traditional Chinese medicine Pingchuan aerosol has a definite curative effect on acute asthma attacks and is effective for both heat asthma and cold asthma, indicating that the curative effect has little connection with the syndrome type.

[0069] Although the present invention has been specifically shown and described with reference to the preferred embodiments, those skilled in the art should understand that various changes in form and details may be made to the present invention without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

1. A new compound traditional Chinese medicine anti-asthma aerosol, characterized in that, The aerosol is prepared from the following raw materials in parts by weight: 10 - 60 parts of Pogostemon cablin, 10 - 60 parts of dried tangerine peel, 10 - 60 parts of Magnolia officinalis, and 10 - 60 parts of Perilla frutescens leaves.

2. The novel compound traditional Chinese medicine pingchuan aerosol according to claim 1, wherein: The weight ratio of Pogostemon cablin, dried tangerine peel, Magnolia officinalis, and Perilla frutescens leaves is 1:1:1:

1.

3. The preparation method of a novel compound traditional Chinese medicine pingchuan aerosol according to claim 1 or 2, characterized in that, It includes the following steps: S1. Weigh Pogostemon cablin, dried tangerine peel, Magnolia officinalis, and Perilla frutescens leaves in parts by weight, totaling 200 parts, add 8 times the weight of water and soak for 0.3 - 1 h to obtain a medicinal material soaking mixture. S2. Distill the medicinal material soaking mixture in step S1, collect 100 ml of aromatic water, store it separately, let it cool and reserve for later use. S3. Reflux extract the distilled medicinal material soaking mixture for 0.8 - 1.5 h and then filter, concentrate the medicinal liquid to 200 ml. S4. After cooling the concentrated medicinal liquid, add an organic solvent to make the organic solvent content in the medicinal liquid reach 55% - 70%, let it stand for 18 - 30 h and then filter, recover the organic solvent to obtain an extract. S5. Combine the extract with the aromatic water, the ratio of the extract to the aromatic water is 1:1, add water to make up the volume to 200 ml, add 1% non - ionic surfactant and 0.05% preservative, mix well and fill into containers, then press in a propellant or compressed air to obtain the new compound traditional Chinese medicine anti - asthma aerosol.

4. The preparation method of a novel compound traditional Chinese medicine pingchuan aerosol as described in claim 3, characterized in that: In step S2, decoct the medicinal material soaking mixture for 0.8 - 1.2 h, filter and concentrate the decoction to 200 ml, cool it and add absolute ethanol to make the alcohol content in the concentrated liquid reach 65% - 70%, and collect 100 ml of aromatic water by steam distillation method.

5. The preparation method of a novel compound traditional Chinese medicine pingchuan aerosol according to claim 3, characterized in that: In step S4, the organic solvent is absolute ethanol.

6. The preparation method of a novel compound traditional Chinese medicine antiasthmatic aerosol according to claim 3, characterized in that: In step S5, the non - ionic surfactant is Tween 80.

7. The preparation method of a novel compound traditional Chinese medicine pingchuan aerosol according to claim 3, characterized in that: In step S5, the preservative is ethyl paraben.

8. The preparation method of a novel compound traditional Chinese medicine pingchuan aerosol as claimed in claim 3, characterized in that: In step S5, the propellant is hydrofluoroalkane.

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