CN114558066A

CN114558066A - Pharmaceutical composition for treating cough variant asthma and preparation method thereof

Info

Publication number: CN114558066A
Application number: CN202210313296.7A
Authority: CN
Inventors: 陆洋; 杜守颖; 阮越勇
Original assignee: Beijing University of Chinese Medicine
Current assignee: Beijing University of Chinese Medicine
Priority date: 2022-03-28
Filing date: 2022-03-28
Publication date: 2022-05-31
Anticipated expiration: 2042-03-28
Also published as: CN114558066B

Abstract

The invention discloses a pharmaceutical composition for treating cough variant asthma and a preparation method thereof, wherein the pharmaceutical composition comprises the following raw materials in parts by weight: 12-30 parts of perilla leaf and 6-15 parts of dried orange peel; a method of preparing a pharmaceutical composition for treating cough variant asthma comprising the steps of: mixing the raw material components with water, heating and leaching; the heating extraction comprises decocting with strong fire, decocting with slow fire, and filtering to obtain extractive solution. The perilla leaf and the dried orange peel are matched with each other, have the effects of dispelling wind, relieving exterior syndrome, strengthening spleen and relieving cough, and are more beneficial to treating cough variant asthma.

Description

Pharmaceutical composition for treating cough variant asthma and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a pharmaceutical composition for treating cough variant asthma and a preparation method thereof.

Background

Cough Variant Asthma (CVA) is one of the most common respiratory diseases causing chronic cough, a special type of asthma in which CVA is predominantly or exclusively clinically manifested as chronic cough. In the early stage of asthma, about 5-6% of cases are mainly manifested as persistent cough, and more often as irritant cough at night or in the morning. The incidence of CVA is divided into two major factors, the first being subjective factors including: genetic, immunological, psychopsychological, endocrine, and health status, etc.; the second objective factor includes: allergens, viral infections, occupational factors, climate, drugs, exercise and diet are also important factors in the development of CVA.

CVA is the most representative disease of intractable cough, and three treatment drugs are commonly used clinically, the first: a bronchodilator; secondly, the method comprises the following steps: inhaled or oral glucocorticosteroids; thirdly, the method comprises the following steps: a leukotriene receptor antagonist. CVA symptoms are improved mainly by bronchiectasis and anti-inflammatory action, but there are damages to cardiovascular, endocrine, metabolic and skeletal systems in long-term application. The american acap (american academy of chests) guidelines state that the vast majority of CVA patients are effective on inhaled bronchodilator and inhaled glucocorticoid therapy. The medicines approved to be on the market at present comprise suliprole, Xinbikebao and the like, and can relax the bronchus by regulating and controlling inflammatory factors, thereby reducing high reaction of the airways, but also has the problem of easy relapse after stopping the medicine. The continuing search for and development of CVA therapeutic drugs should be the focus of research on this disease. For the reasons, a few CVA patients want to find the traditional Chinese medicine for treating CVA, and the market of traditional Chinese medicines specially used for treating CVA is not abundant.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition for treating cough variant asthma and a preparation method thereof, and aims to solve the problems in the background art.

In order to achieve the purpose, the invention provides the following technical scheme:

a pharmaceutical composition for treating cough variant asthma comprises the following raw materials in parts by weight: 12-30 parts of perilla leaf and 6-15 parts of dried orange peel.

On the basis of the technical scheme, the invention also provides the following optional technical scheme:

in one alternative: the raw materials also comprise 12-30 parts of perilla fruit, 6-15 parts of pummelo peel, 6-9 parts of cicada slough, 6-15 parts of schizonepeta and 3-8 parts of liquorice.

In one alternative: the composite material comprises the following raw materials in parts by weight: 24 parts of perilla leaf, 12 parts of dried orange peel, 24 parts of perilla seed, 12 parts of pummelo peel, 8 parts of cicada slough, 12 parts of schizonepeta and 6 parts of liquorice.

A method of preparing a pharmaceutical composition for treating cough variant asthma as described above, comprising the steps of: mixing the raw material components with water, heating and leaching; the heating extraction comprises decocting with strong fire, and decocting with slow fire to obtain extractive solution.

In one alternative: the weight ratio of the raw material components to the water is 1: (8-12).

In one alternative: the time for boiling before strong fire is 20-30min and the time for boiling before slow fire is 15-20 min.

In one alternative: repeating the simmering for at least two times, and combining the liquid materials boiled with the simmering for each time; when the raw materials are boiled with slow fire for the second time, the addition amount of the water is 5-8 times of the mass of the raw materials.

In one alternative: concentrating the extractive solution to 0.20-0.27 g/mL.

In one alternative: before the raw materials are heated, the raw material components are soaked for 20-30 min.

Compared with the prior art, the invention has the following beneficial effects:

the perilla leaf and the dried orange peel are matched with each other, have the effects of dispelling wind, relieving exterior syndrome, strengthening spleen and relieving cough, and are more beneficial to treating cough variant asthma.

The preparation method of the pharmaceutical composition for treating CVA is simple and easy to operate, and the pharmaceutical composition for treating CVA obtained by the method has good treatment effect on CVA.

Drawings

FIG. 1 is a schematic diagram of the determination of cough frequency for each group of rats according to the present invention;

FIG. 2 is a schematic diagram showing the conventional EOS change of pulmonary blood of rats in each group according to the present invention;

FIG. 3 is a schematic representation of pulmonary airway resistance of groups of rats according to the present invention;

FIG. 4 is a schematic representation of lung compliance of rats in various groups according to the present invention;

FIG. 5 is a schematic representation of the morphological changes of the lung tissue of various groups of rats according to the present invention;

FIG. 6 is a graph showing a comparison of the number of IgE molecules in lung tissue of rats in each group according to the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail by the following examples. The examples are given solely for the purpose of illustration and are not intended to limit the scope of the invention. Any obvious modifications or variations can be made to the present invention without departing from the spirit or scope of the present invention.

Example one

A pharmaceutical composition for treating cough variant asthma comprises the following raw materials:

12g of perilla leaf and 6g of dried orange peel;

a method of preparing a pharmaceutical composition for treating cough variant asthma comprising the steps of:

(a) mixing folium Perillae and pericarpium Citri Tangerinae, soaking in water for 20min, decocting with strong fire for 20min, decocting with slow fire for 15min, and filtering to obtain medicinal liquid;

the weight ratio of the medicine components to the water is 1: 10;

(b) adding water into the decoction dregs in the step (a), decocting the decoction dregs for 10min by slow fire, collecting liquid medicines of the two times, and concentrating the liquid medicines together;

the addition amount of the water is 5 times of the mass of the components of the medicine raw material;

and concentrating the decocted liquid medicine until the concentration of the crude drug is 0.2 g/mL.

Example two

18g of perilla leaf and 9g of dried orange peel;

the weight ratio of the medicine components to the water is 1: 10;

(b) adding water into the dregs in the step (a), decocting the dregs for 10min by slow fire, collecting liquid medicines of the two times, and concentrating the liquid medicines together;

the addition amount of the water is 6 times of the mass of the components of the medicine raw materials;

EXAMPLE III

30g of perilla leaf and 15g of dried orange peel;

(a) mixing folium Perillae and pericarpium Citri Tangerinae, soaking in water for 30min, decocting with strong fire for 25min, then with slow fire for 15min, and filtering to obtain medicinal liquid;

the weight ratio of the medicine components to the water is 1: 12;

(b) adding water into the dregs in the step (a), decocting for 20min by slow fire, collecting liquid medicines of the two times, and concentrating together;

the addition amount of the water is 7 times of the mass of the components of the medicinal raw materials;

Example four

12g of perilla leaf, 6g of dried orange peel, 12g of perilla seed, 6g of pummelo peel, 6g of cicada slough, 6g of schizonepeta and 3g of liquorice;

the preparation method of the pharmaceutical composition for treating cough variant asthma comprises the following steps:

(a) mixing folium Perillae, pericarpium Citri Tangerinae, fructus Perillae, exocarpium Citri Grandis, periostracum Cicadae, herba Schizonepetae, and Glycyrrhrizae radix, soaking in water for 30min, decocting with strong fire for 25min, decocting with slow fire for 15min, and filtering to obtain medicinal liquid;

the weight ratio of the medicine components to the water is 1: 10;

(b) adding water into the dregs in the step (a), decocting for 15min by slow fire, collecting liquid medicines of the two times, and concentrating together;

the addition amount of the water is 8 times of the mass of the components of the medicinal raw materials;

and concentrating the decocted liquid medicine until the concentration of the crude drug is 0.27 g/mL.

EXAMPLE five

16g of perilla leaf, 8g of dried orange peel, 16g of perilla seed, 8g of pummelo peel, 7g of cicada slough, 6g of schizonepeta and 5g of liquorice;

the weight ratio of the medicine components to the water is 1: 10;

the addition amount of the water is 8 times of the mass of the components of the medicine raw materials;

EXAMPLE six

18g of perilla leaf, 9g of dried orange peel, 18g of perilla seed, 9g of pummelo peel, 6g of cicada slough, 9g of schizonepeta and 3g of liquorice;

(a) mixing folium Perillae, pericarpium Citri Tangerinae, fructus Perillae, exocarpium Citri Grandis, periostracum Cicadae, herba Schizonepetae, and Glycyrrhrizae radix, soaking in water for 30min, decocting with strong fire for 30min, decocting with slow fire for 20min, and filtering to obtain medicinal liquid;

the weight ratio of the medicine components to the water is 1: 10;

EXAMPLE seven

20g of perilla leaf, 10g of dried orange peel, 20g of perilla seed, 10g of pummelo peel, 7g of cicada slough, 10g of schizonepeta and 6g of liquorice;

the weight ratio of the medicine components to the water is 1: 10;

Example eight

24g of perilla leaf, 12g of dried orange peel, 24g of perilla seed, 12g of pummelo peel, 8g of cicada slough, 12g of schizonepeta and 6g of liquorice;

the weight ratio of the medicine components to the water is 1: 10;

Example nine

30g of perilla leaf, 15g of dried orange peel, 30g of perilla seed, 15g of pummelo peel, 9g of cicada slough, 15g of schizonepeta and 8g of liquorice;

the weight ratio of the medicine components to the water is 1: 10;

Experimental verification

An egg protein and aluminum hydroxide induced cough variant asthma-like rat model was used. 36 SD male rats provided by Beijing Wintonli Huake technology laboratory animal technology Co., Ltd. have a body mass of 75-92 g. The experimental animals have licenses for use.

Rats were sensitized by intraperitoneal injection of a 10% OVA and AL (OH)3 mixed solution 1ml on

days

1 and 8, respectively. Atomizing for 30min by 20 mL (1% OVA) every day from 15 th to 30 th day;

rats were randomly divided into a blank group (KB), a model group (MX), a positive drug (YX), a lung-spleen cough 1 formula (FP1) group, and a lung-spleen cough 2 formula (FP2) group by a digital table method, and were raised in a single cage in an Independent Ventilation Cage (IVC). (lung spleen cough 1 prescription, composed of 30g of perilla leaf and 15g of dried orange peel, lung spleen cough 2 prescription, composed of 12g of perilla leaf, 6g of dried orange peel, 12g of perilla seed, 6g of pummelo peel, 6g of cicada slough, 6g of schizonepeta and 3g of liquorice);

from day 15 to day 30, the dose was converted from adult dose (60kg) to half rat dose, KB group: 1ml/100g/d of intragastric distilled water is divided into 1 time per day; MX group: 1ml/100g/d of intragastric distilled water is divided into 1 time per day; group YX: intragastric administration of the Montelukast sodium chewable tablet (concentration 6 mg/kg) is 0.4ml/100g/d, and the administration is divided into 1 time per day; FP1 group: 1ml/100g/d of 1 prescription decoction (concentration is 2.4 g/kg) for treating gastric lavage, lung and spleen cough, and is divided into 1 time per day; FP2 group: 1ml/100g/d of enema, lung and spleen cough 2 formula decoction (concentration 2.4 g/kg) is divided into 1 time per day.

1. Cough variant asthma model rat cough status

As shown in the following table and figure 1, after 4, 9 and 13 days of drenching administration of the two formulations, the symptoms associated with cough in rats were significantly relieved, as shown in the following table: the nose is grabbed, the head is nodded, and the weight is obviously reduced; in addition, the occurrence, abdominal muscle extraction, and respiratory acceleration symptoms are also controlled. After the 4 th day of administration, there was no significant change in symptoms associated with the number of coughs in the rats. The experiment for measuring the cough frequency on the 9 th day shows that the cough related symptoms are initially relieved after the two prescriptions are infused, and the difference has statistical significance (P is less than 0.05). The frequency test of cough on day 13 shows that the cough related symptoms are relieved after the two prescriptions are irrigated, particularly the lung and spleen cough 2 prescriptions are obviously relieved, and the difference has statistical significance (P < 0.05 or P < 0.01).

Thus, it can be seen that: the lung and spleen cough prescription can relieve the change of symptoms related to cough of a cough variant asthma model rat induced by egg protein and aluminum hydroxide. Compared with the intervention effect of the lung and spleen cough 2 formula on cough variant asthma, the early 2 formulas can effectively inhibit and improve the symptoms related to rat cough, and the lung and spleen cough 2 formula can inhibit the symptoms related to cough more obviously.

Cough frequency determination Table 1 (day 4 of drug intervention)

Cough frequency determination table (medicine intervention day 9)

Cough frequency determination table (13 th day of medicine intervention)

2. Lung and spleen cough prescription for inhibiting eosinophilic granulocyte in blood routine

As shown in the table below and figure 2, the EOS in the rat blood was significantly reduced after 4, 9, 13 days of drench administration of the two formulations. There was no significant change in EOS after day 4 of dosing. Routine EOS was measured from day 9 and found that EOS began to decrease after infusion of both groups, with statistical differences (P < 0.05). The conventional EOS of blood measurement on the 13 th day shows that the EOS of the two groups of prescriptions is obviously reduced after the infusion, and the difference has statistical significance (P is less than 0.01).

It can be seen that the longer the intervention time of the two formulas of lung and spleen cough is, the more obvious the inhibition of the increase of eosinophils of the rat in the cough variant asthma model induced by ovalbumin and aluminum hydroxide is.

Eosinophil percentage (%) (day 4 of drug intervention)

Eosinophil percentage (%) (day 9 of drug intervention)

Eosinophil percentage (%) (day 13 of drug intervention)

3. Lung-spleen cough prescription for improving egg protein induced cough variant asthma model rat airway resistance and lung compliance

Referring to the attached

drawings

3 and 4, by the lung function detection technology, when the lung function airway resistance is detected, compared with a model group, 2 formulas for lung spleen cough can effectively reduce the airway resistance, and the difference has statistical significance (P is less than 0.05), so that the lung ventilation capability is improved. Compared with the model group, 2 groups of formulas for treating lung and spleen cough can effectively improve lung compliance, and the difference has statistical significance (P is less than 0.01).

Airway Resistance (RI)

Compliance of the lung (Cdyn)

4. Lung and spleen cough prescription for improving ovalbumin-induced cough variant asthma model rat lung tissue morphological change

The lung tissue sections of the rats of each group on day 14 were subjected to HE staining and light microscopic comparison, as shown in FIG. 5; in the normal group, inflammatory cell infiltration is not seen in the lung tissue gaps, the bronchial wall is intact without thickening, and the bronchial cavities and alveolar cavities have no exudates. Compared with the normal group, the model group has a large amount of inflammatory cell infiltration, the bronchial smooth muscle is thickened, and the secretion of bronchial mucus is increased. Through the intervention of various groups of medicines in the lung and spleen cough prescription, especially after the lung and spleen cough 2 prescription is used for dry prognosis, the number of inflammatory cells is obviously reduced, the smooth muscle of the bronchus is thickened, and the mucus of the bronchus is obviously improved.

In conclusion, 2 formulas for treating lung and spleen cough can obviously reduce inflammatory cells, and relieve bronchial smooth muscle thickening and bronchial mucus secretion; the lung and spleen cough prescription 2 is most obvious in reducing inflammatory cells and bronchial smooth muscle thickening.

5. Lung and spleen cough prescription inhibiting ovum protein induced cough variant asthma model rat allergic reaction and inflammatory factor condition

Referring to FIG. 6, the ELISA kit can detect IFN, IL-4 and IL-13 in the blood of each group of rats: the number of IL-4 and IL-13 in lung injury tissues of rats in the lung spleen cough prescription is lower than that of model groups (P < 0.05 or P < 0.01). The test of allergic IFN and the reaction key antibody IgE in the blood of each group of rats by an ELISA kit can find that: the number of IgE in lung tissues of rats in lung spleen cough prescription is lower than that of rats in model group (P < 0.05).

The lung and spleen cough prescription can inhibit egg protein and aluminum hydroxide induced cough variant asthma model rat allergic reaction and inflammatory factor. Compared with the inhibition effect of the lung and spleen cough 2 groups of prescriptions on verification and allergic reaction, the inhibition effect of the lung and spleen cough 2 prescription on inflammatory reaction is found to be slightly superior to that of the lung and spleen cough 1 prescription.

In conclusion, the lung and spleen cough various formulas can obviously improve the obvious reduction of the number of inflammatory cells of a cough variant asthma model, the thickening of bronchial smooth muscle, the obvious improvement of bronchial mucus and the relief of bronchial inflammation and anaphylaxis. The lung spleen cough 1 prescription is more remarkable in improving the bronchial smooth muscle thickening and bronchial mucus of cough variant asthma, after the 13 th day, the cough symptom score is lower than that of a contemporary model group, and the eosinophil count is obviously lower than that of the model group, and the result shows that: the lung and spleen cough 1 prescription has obvious effect of inhibiting the airway hyperreaction and inflammatory reaction of cough variant asthma, and achieves the effects of strengthening spleen and relieving cough; the lung and spleen cough 2 prescription has the most prominent effect of relieving the thickening of the smooth muscle of the bronchial tube of the cough variant asthma, and the prescription intervenes inflammatory cells of the airway tissue injury, inhibits inflammatory factors and allergy-related antibodies, and thus inhibits the airway hyperresponsiveness. In addition, eosinophils, which are critical to the cough variant asthma, were also significantly controlled after taking the formula of lung-spleen cough 2. The method can relieve pulmonary function airway obstruction of rat and improve pulmonary compliance. Thereby improving the symptoms related to the cough of the rats and improving the living quality of the rats, which is probably related to the lung tonifying, spleen strengthening, wind dispelling and cough relieving of the medicament, thereby inhibiting the source of cough and inflammatory reaction. The traditional Chinese medicine composition has excellent treatment effect on different syndrome characteristics of cough variant asthma on the functions of tonifying lung and spleen, dispelling wind and relieving cough of the same core formula.

The above description is only for the specific embodiments of the present disclosure, but the scope of the present disclosure is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present disclosure, and all the changes or substitutions should be covered within the scope of the present disclosure. Therefore, the protection scope of the present disclosure shall be subject to the protection scope of the claims.

Claims

1. A pharmaceutical composition for treating cough variant asthma, which is characterized by comprising the following raw materials in parts by weight: 12-30 parts of perilla leaf and 6-15 parts of dried orange peel.

2. The pharmaceutical composition for treating cough variant asthma according to claim 1, wherein said raw materials further comprise 12-30 parts of perilla fruit, 6-15 parts of exocarpium citri grandis, 6-9 parts of periostracum cicadae, 6-15 parts of schizonepeta and 3-8 parts of licorice.

3. The pharmaceutical composition for treating cough variant asthma according to claim 2, comprising the following raw materials in parts by weight: 24 parts of perilla leaf, 12 parts of dried orange peel, 24 parts of perilla seed, 12 parts of pummelo peel, 8 parts of cicada slough, 12 parts of schizonepeta and 6 parts of liquorice.

4. A method of preparing a pharmaceutical composition for the treatment of cough variant asthma as claimed in any one of claims 1 to 3, comprising the steps of: mixing the raw material components with water, heating and leaching; the heating extraction comprises decocting with strong fire, decocting with slow fire, and filtering to obtain extractive solution.

5. The method of preparing a pharmaceutical composition for the treatment of cough variant asthma according to claim 4, wherein the weight ratio of said raw material components to said water is 1: (8-12).

6. The method of preparing a pharmaceutical composition for the treatment of cough variant asthma according to claim 4, wherein said precooking with strong fire is 20-30min and precooking with slow fire is 15-20 min.

7. The method of preparing a pharmaceutical composition for the treatment of cough variant asthma according to claim 4, wherein said simmering is repeated at least twice and the individual simmering streams are combined; when the raw materials are boiled with slow fire for the second time, the addition amount of the water is 5-8 times of the mass of the raw materials.

8. The method of preparing a pharmaceutical composition for the treatment of cough variant asthma as claimed in claim 4, wherein the extraction liquid is further concentrated after obtaining the extraction liquid, and the extraction liquid is concentrated to 0.20-0.27 g/mL.

9. The method of preparing a pharmaceutical composition for the treatment of cough variant asthma according to claim 4, wherein the soaking of the raw material components is performed for a period of 20-30min prior to said heating of the raw material.