CN114748558B

CN114748558B - Anti-influenza antipyretic anti-inflammatory traditional Chinese medicine composition and preparation method and application thereof

Info

Publication number: CN114748558B
Application number: CN202210535773.4A
Authority: CN
Inventors: 张伟; 孟兆青; 罗毅; 张荣飞; 秦金淼; 刘子夜; 许蕊蕊; 曹桂云; 姚元成; 李樱
Original assignee: Shandong Hongjitang Pharmaceutical Group Co ltd
Current assignee: Shandong Hongjitang Pharmaceutical Group Co ltd
Priority date: 2022-05-17
Filing date: 2022-05-17
Publication date: 2023-05-26
Anticipated expiration: 2042-05-17
Also published as: CN114748558A

Abstract

The application discloses an anti-influenza, antipyretic and anti-inflammatory traditional Chinese medicine composition, and a preparation method and application thereof, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 12-60 parts of honeysuckle stem, 12-60 parts of dyers woad leaf, 12-60 parts of radix isatidis, 12-60 parts of dandelion, 3-15 parts of calyx seu fructus physalis and 3-15 parts of saussurea involucrata leaf. The traditional Chinese medicine composition has obvious anti-influenza virus effect and simultaneously has excellent antipyretic and anti-inflammatory effects.

Description

Anti-influenza antipyretic anti-inflammatory traditional Chinese medicine composition and preparation method and application thereof

Technical Field

The application relates to an anti-influenza antipyretic anti-inflammatory traditional Chinese medicine composition and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparation.

Background

Influenza (Influenza) is an acute febrile respiratory infectious disease caused by Influenza virus, and is transmitted by spray, and clinically typical symptoms of systemic poisoning such as protrusion aversion to cold, high fever, headache, general ache, fatigue and the like are manifested, while respiratory symptoms are lighter. The disease is usually self-limiting, and the course of the disease is usually 3-4 days. Infant, elderly, patient with cardiopulmonary disease and other chronic diseases or immunocompromised person can complicated pneumonia, prognosis is poor. Under the control of hypothalamic thermoregulation center, normal body always keeps dynamic balance of heat generation and heat dissipation, and when body is under pyrogenic effect, the dynamic balance is unbalanced to cause fever. Fever is in fact a mechanism by which the body protects its physiological functions from normal operation. As body temperature increases, some pathogenic microbial activities become less active and slow down. The immune system response of the human body is obviously enhanced. But the long-term heating can have serious consequences. And thus is also particularly important for the treatment of fever. In addition, inflammation is a common symptom in influenza, inflammation is an important defense mechanism generated after body tissues are subjected to various stimulation and injury, inflammatory response is the most basic anti-injury response of the body, and acute inflammation usually has changes such as red, swelling, heat, diseases, dysfunction and the like.

The traditional Chinese medicine for treating influenza has the advantages that western medicines are easy to generate drug resistance, part of traditional Chinese medicines have anti-influenza virus curative effect, generally have no drug resistance, but have single effect, are difficult to treat concurrent diseases at the same time, and have low effect taking speed, so that the development of a novel traditional Chinese medicine composition with comprehensive treatment effect is particularly important, and has great market development potential.

Disclosure of Invention

In order to solve the problems, the traditional Chinese medicine composition for resisting influenza, relieving fever and resisting inflammation, the preparation method and the application thereof are provided, and the traditional Chinese medicine composition has obvious anti-influenza virus effect and simultaneously has excellent antipyretic and anti-inflammatory effects.

According to one aspect of the application, the anti-influenza, antipyretic and anti-inflammatory traditional Chinese medicine composition is provided, and is prepared from the following raw materials in parts by weight: 12-60 parts of honeysuckle stem, 12-60 parts of dyers woad leaf, 12-60 parts of radix isatidis, 12-60 parts of dandelion, 3-15 parts of calyx seu fructus physalis and 3-15 parts of saussurea involucrata leaf.

Optionally, the composition further comprises 0.2-0.4 part by weight of maltodextrin and 0.1-0.5 part by weight of stevioside.

Optionally, the feed additive is prepared from the following raw materials in parts by weight: 12-60 parts of honeysuckle stem, 12-60 parts of dyers woad leaf, 12-60 parts of radix isatidis, 12-60 parts of dandelion, 3-15 parts of calyx seu fructus physalis, 3-15 parts of saussurea involucrata, 0.2-0.4 part of maltodextrin and 0.1-0.5 part of stevioside.

Optionally, the weight ratio of the honeysuckle stem, the dyers woad leaf, the radix isatidis, the dandelion, the calyx seu fructus physalis and the sauropus drily leaf is 4:4:4:1:1 in sequence.

Preferably, the feed additive is prepared from the following raw materials in parts by weight: 60 parts of honeysuckle stem, 60 parts of dyers woad leaf, 60 parts of radix isatidis, 60 parts of dandelion, 15 parts of calyx seu fructus physalis, 15 parts of saussurea involucrata leaf, 0.3 part of maltodextrin and 0.5 part of stevioside.

According to still another aspect of the present application, there is provided a preparation method of the above-mentioned Chinese medicinal composition, comprising the steps of:

(1) Mixing caulis Lonicerae, folium Isatidis, radix Isatidis, herba Taraxaci, calyx seu fructus physalis and folium saussureae involucratae, placing into a decocting pot, soaking in water, decocting, and filtering to obtain a first decoction;

(2) Adding water into a decoction pot for decoction, and filtering to obtain a second decoction;

(3) Combining the first decoction and the second decoction, and filtering to obtain a third decoction;

(4) Heating and concentrating the third decoction, filtering, adding maltodextrin and stevioside, drying, and granulating.

Optionally, the water adding amount in the step (1) is 12-16 times of the total amount of the traditional Chinese medicinal materials in the step, and the water adding amount in the step (2) is 10-14 times of the total amount of the traditional Chinese medicinal materials in the step.

Optionally, the soaking time in the step (1) is 0.2-1h, and the decocting time is 0.2-1h; the decoction time of the step (2) is 0.2-1h.

Optionally, in step (4), the third decoction is concentrated to a relative density of 1.09-1.11.

Optionally, the drying method in the step (4) is spray drying, and granulating after spraying the dry powder and sieving with a 80-120 mesh sieve.

Preferably, the concentration temperature in the step (4) is 60 ℃, and the dry paste rate is 25.2% -30.8%.

According to still another aspect of the application, there is provided an application of the above traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above preparation method, wherein the traditional Chinese medicine composition is used for preparing anti-influenza, antipyretic and anti-inflammatory medicines.

Benefits of the present application include, but are not limited to:

1. the anti-influenza, antipyretic and anti-inflammatory traditional Chinese medicine composition has obvious anti-influenza virus effect and simultaneously has excellent antipyretic and anti-inflammatory effects,

2. according to the anti-influenza, antipyretic and anti-inflammatory traditional Chinese medicine composition, honeysuckle stem is sweet and cold, has the effects of dispelling wind and clearing lung heat, and is a monarch drug; the dyers woad leaf and the dyers woad root assist in clearing upper-jiao heat, are good at clearing heat in blood, can relieve sore throat and remove spots, and are ministerial drugs; the dandelion and the calyx seu fructus physalis can clear heat and induce diuresis to treat stranguria, so that heat can be discharged from urine, and the two medicines have the effects of relieving swelling, resolving masses, relieving sore throat and reducing phlegm, and have obvious effect of relieving symptoms; the sauropus has the effects of sweet and bland taste and lung moistening, avoids damaging lung yin by heat, and simultaneously has the effect of relaxing bowels, so that heat can be discharged from stool, and the sauropus is used as an adjuvant.

The six herbs are combined to clear lung heat and clear heat of upper, middle, lower and triple energizer, so as to clear heat of qi and blood, and remove heat from the interior and relieve constipation. The traditional Chinese medicine composition is special for clearing heat to treat the disease, and simultaneously has the effects of dispelling wind, relieving sore throat, relieving swelling, relieving cough, reducing sputum and relieving symptoms, and clearing heat and protecting yin, so that evil is removed without hurting healthy energy.

3. According to the preparation method of the anti-influenza antipyretic anti-inflammatory traditional Chinese medicine composition, the preparation method is simple and easy to operate, the loss of active ingredients of medicinal materials can be reduced, and the production cost is low.

Drawings

The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this application, illustrate embodiments of the application and together with the description serve to explain the application and do not constitute an undue limitation to the application. In the drawings:

FIG. 1 is a bar graph of the effect of a desired list on the body weight of mice infected with influenza virus (3 dpi administration), the body weight of each group of mice when Balb/c mice were infected with influenza virus 3 dpi;

FIG. 2 is a graph showing the weight change trend of mice infected with influenza virus (3 dpi administration), balb/c mice infected with influenza virus, and 0-3dpi mice in each group;

FIG. 3 is a bar graph of the effect of a desired dose of the anti-influenza virus on the body weight of mice infected with influenza virus (7 dpi administration), balb/c mice infected with influenza virus, and body weight of each group of mice at 7 dpi;

FIG. 4 is a graph showing the weight change trend of mice infected with influenza virus (7 dpi administration), balb/c mice infected with influenza virus, and 0-7dpi mice in each group;

FIG. 5 is a bar graph of the effect of a desired de-tabulated formulation on lung index of mice infected with influenza virus (3 dpi administration), balb/c mice infected with influenza virus, and lung index (lung weight/body weight) was calculated for each group at 3 dpi;

FIG. 6 is a bar graph of the effect of a happy tabulated prescription on lung index of mice infected with influenza virus (7 dpi administration), balb/c mice infected with influenza virus, and lung index (lung weight/body weight) was calculated for each group at 7 dpi;

FIG. 7 is a photograph of lung lesions of mice infected with influenza virus as indicated by the formula of relief (3 dpi administration);

FIG. 8 is a photograph of lung lesions of mice infected with influenza virus as indicated by the formula of relief (7 dpi administration);

FIG. 9 is a graph showing the temperature change of different LPS-heated rats.

Detailed Description

The present application is described in detail below with reference to examples, but the present application is not limited to these examples.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The reagents or materials used in the present invention may be purchased in conventional manners, and unless otherwise indicated, they may be used in conventional manners in the art or according to the product specifications. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred methods and materials described in this patent are illustrative only.

Medicinal material description used in this application:

1. medicinal material base source and production place processing

Caulis Lonicerae: the product is dried stem and branch of Lonicera japonica Lonicera japonica thunder. Collected in autumn and winter, and dried in the sun.

Folium Isatidis: the product is dried leaf of Isatis indigotica fort. Harvesting for 2-3 times in summer and autumn, removing impurities, and sun drying.

Radix Isatidis: the product is dry root of Isatis indigotica fort. The autumn is to dig, remove sediment and dry in the sun.

Dandelion: the product is dried whole herb of Taraxacum mongolicum Taraxacum mongolicum hand-Mazz. The flowers are excavated from spring to autumn, impurities are removed, cleaned and dried in the sun.

Brocade lantern: the product is dried calyx of Physalis alkekengiil. Var. Franketii (Mast.) Makino or calyx with fruit of Solanaceae. Harvesting in autumn when fruit is ripe and calyx is red or orange red, and drying.

Leaf of Dragon's foot: the product is dried leaf of sauropus spinosus of Euphorbiaceae. Collected in summer and autumn, and dried in the sun.

2. Medicinal material producing area

All the six medicinal materials are cultivated manually, and wild resources are not involved. According to the evaluation of medicinal material resources, the current planting area and the yield meet the medicinal material demand within 5 years after the variety is marketed.

The fixed producing area of the honeysuckle stem is Pingyi county in Shandong province and Yi-Yu county in Shandong province and Mi county in Henan province.

The fixed producing areas of dandelion are Anhui, gansu, hebei and Henan.

The fixed producing areas of the dyers woad leaf are Hebei, gansu and Anhui.

The fixed producing areas of the radix isatidis are Hebei, gansu and Anhui.

The calyx seu fructus physalis fixed producing areas are Jilin, hebei and Xinjiang.

The fixed production places of the sauropus are Guangxi, guangdong and Hainan.

3. The dry paste rate calculating method comprises the following steps: 50ml of the orthogonal test extract was taken and placed in evaporating dishes (M) ₁ ) Evaporating in water bath, drying at 105deg.C in oven for 3 hr, taking out, cooling in dryer for 30min, and rapidly and precisely weighing (M ₂ ) The dry extract rate is calculated according to the following formula, wherein M is the mass of the prescription medicinal material, and V is the volume (ml) of the extracting solution.

EXAMPLE 1 Chinese medicinal composition 1# particles

The preparation method comprises the following steps: 60g of honeysuckle stem, 60g of dyers woad leaf, 60g of radix isatidis, 60g of dandelion, 15g of calyx seu fructus physalis, 15g of saussurea involucrata leaf, 0.3g of maltodextrin and 0.5g of stevioside.

The preparation method comprises the following steps:

(1) Mixing caulis Lonicerae, folium Isatidis, radix Isatidis, herba Taraxaci, calyx seu fructus physalis and folium saussureae involucratae, placing into a decocting pot, soaking in water with water amount of 14 times of the total amount of the Chinese medicinal materials, decocting for 0.5 hr, and filtering to obtain first decoction;

(2) Adding water into a decoction pot for decoction, wherein the water adding amount is 12 times of the total amount of the traditional Chinese medicinal materials in the step, the decoction time is 0.5h, and filtering to obtain a second decoction;

(4) Heating and concentrating the third decoction to a relative density of 1.09-1.11, filtering, adding maltodextrin and stevioside, spray drying, spraying the dry powder, sieving with 80-120 mesh sieve, and granulating to obtain 100g of Chinese medicinal composition 1# granule.

Traits: brown to tan particles; slightly sweet and bitter.

Example 2 anti-influenza experiment of Chinese medicinal composition 1#

1. Purpose of experiment

The efficacy of the drug for treating influenza is evaluated according to the improvement effect of the drug on influenza virus infected mice body weight, lung index, lung tissue and throat lesions.

2. Experimental materials and methods

2.1 laboratory animals and Virus strains

The index of experimental animals is shown in table 1, the virus strain is influenza A virus PR8 strain, and the laboratory is frozen.

TABLE 1 animal index of experiment

2.2 pharmaceutical products and reagents

The experimental drugs are shown in Table 2, and the experimental reagents comprise physiological saline and PBS.

Table 2 experimental drugs

2.3 instrument consumables

The experimental instrument is shown in table 3, and the experimental consumables are shown in table 4.

Table 3 laboratory apparatus

Sequence number	Name of the name	Model number
				1	Electronic balance	EX225ZH/AD
2	Ice machine	SZB-100
			3	Centrifugal machine	5424R
4	Vortex mixing instrument	MX-S
			5	Electronic balance	YP600
7	Biological safety cabinet	HFsafe-1500
			8	Biological safety cabinet	HFsafe-1500LC

Table 4 experiment consumable

2.4 Experimental grouping and administration

The animals were grouped and infected and dosed as shown in table 5.

TABLE 5 grouping and infection, dosing of animals

* Dosage of administration: the dosage of the traditional Chinese medicine composition 1# particles is 10 g/day for clinical adults twice a day, and the dosage of mice is 9.1× (10000 mg/70 Kg) =1300 mg/Kg (clinical equivalent dosage) calculated by 70Kg of adult human body.

In the experiment, the mice of the traditional Chinese medicine composition 1# particles are provided with 2 doses: clinically equivalent dose (1300 mg/kg) and 5 times clinically equivalent dose (6500 mg/kg).

2.5 Experimental methods

50 healthy SPF-class Balb-c mice, males, 6 weeks old, weighing 16-18g, were selected, and after 3 days of adaptive rearing, were randomly grouped according to body weight, 5 animals per group, 2 parallel groups were arranged per group, and 10 groups were all arranged. Except the control group, PR8 virus strain virus challenge (1 LD 50) was performed by nasal drip, and the administration was performed for 4 hours, 1 time/day, and 3 days or 7 days after the challenge. Animal body weight was recorded daily and animal physical signs were observed. The mice were harvested the next day after dosing. Analysis was performed on the changes in the body weight and lung index (lung weight/body weight) of mice, respectively; lung tissue lesions were observed and recorded.

3. Experimental results

3.1 Effect of Chinese medicinal composition 1# on body weight of mice infected with influenza Virus

3.1.1 effects of 3 days of administration on body weight of mice infected with influenza virus

Specific effects are shown in fig. 1, specific body weight change trends are shown in fig. 2, and specific data are shown in table 6.

Table 63 influence of Chinese medicinal composition # 1 on body weight of mice infected with influenza Virus at dpi (mean.+ -. SD, n=5)

Group of	Body weight (g)
		Control group	19.24±0.47
Model group	17.76±0.62
		Positive medicine group	17.88±0.37
Experiment 1 group	17.68±0.90
		Experiment 2 group	18.54±1.20

3.1.2 Effect of administration of 7dpi on influenza Virus infected mice body weight

Specific effects are shown in fig. 3, specific body weight change trends are shown in fig. 4, and specific data are shown in table 7.

Table 77 influence of Chinese medicinal composition # 1 on body weight of mice infected with influenza Virus at dpi (mean.+ -. SD, n=5)

Group of	Body weight (g)
		Model group	15.48±1.78
Experiment 1 group	14.72±0.78
		Experiment 2 group	15.38±2.29
Positive medicine group	15.06±0.69

The above results indicate that the body weight of mice decreased from day 3 after virus infection, but there was no statistical difference between the body weights of the mice in each group at day 3 and day 7 after challenge.

3.2 Effect of Chinese medicinal composition 1# on pulmonary index of mice infected with influenza Virus

3.2.1. Effect of Chinese medicinal composition 1# on lung index when mice are infected with influenza virus at 3dpi

The lung index is lung weight/body weight, specific effects are shown in fig. 5, and specific data are shown in table 8.

Table 8 effect of chinese medicinal composition 1# on lung index of influenza virus infected mice (mean±sd, n=5)

The results show that compared with the control group, the lung index of the mice in the model group is obviously increased; compared with the model group, the lung index of the mice in the Dafei treatment group of 20mg/kg is obviously reduced, and the lung index of the mice in the 1# treatment group of the Chinese medicinal compositions of 1300mg/kg and 6500mg/kg is reduced, but no statistical difference exists.

3.2.2 Effect of Chinese medicinal composition 1# on pulmonary index in mice infected with influenza Virus at 7dpi

The specific effects are shown in fig. 6 and the specific data are shown in table 9.

Table 9 effect of chinese medicinal composition 1# on lung index of influenza virus infected mice (mean±sd, n=5)

Group of	Lung index
		Control group	0.005788±0.0006205
Model group	0.01312±0.001730
		Experiment 1 group	0.01455±0.001800
Experiment 2 group	0.01307±0.002140
		Positive medicine group	0.01423±0.001924

The results showed that the lung index of the mice in the model group was significantly increased compared to the control group, and that there was no statistical difference between the drug groups compared to the mice in the model group.

3.3 Effect of Chinese medicinal composition 1# on pulmonary lesions

Specific effects are shown in fig. 7 and 8, and the result shows that compared with the normal group, on the 3 rd day after virus infection, the model group mice start to be diseased from the root of the trachea, extend to the lobe of the lung, and the lung tissues are swollen (the lung index result shows that the lung index is remarkably increased). On day 7 post infection, severe lesions occurred in lung tissue.

Compared with the model group, on the 3 rd day after virus infection, the lung swelling of the positive medicine group is reduced (the lung index result shows that the lung index is obviously reduced), but the root of the trachea can still be provided with visible lesions, and the high and low doses of the traditional Chinese medicine composition 1# are not obviously improved. On day 7 after infection, each group had some effect of improving lung tissue lesions (but lung index results showed no significant differences).

Example 3 experiment of the antipyretic effect of Chinese medicinal composition 1# on rat LPS-induced fever model

1. Materials and methods

1.1 laboratory animals

Wistar rats, SPF grade, 54, male and female halves, mass 180-220g, purchased from Beijing Vitolihua laboratory animals Inc. Animal experiments were performed in a Shandong university of traditional Chinese medicine animal experiment center barrier environmental facility (laboratory animal use license number: SYXK 20170022). Meanwhile, during the experiment, all rats are strictly controlled in the same living environment and feeding conditions, and all rats are subjected to adaptive feeding for one week before the experiment starts. During the experiment, rats were given sufficient feed and water, were allowed to ingest drinking water freely, and during the experiment, all rats had free diet and water, with alternating illumination: 12h light/dark period, room temperature 22+ -2deg.C, humidity 55+ -5%. The experimental contents were approved by the animal ethics committee of Shandong university of traditional Chinese medicine (approval number: SDUTCM 20211015002).

1.2 reagents and instruments

The test reagents are shown in Table 10, and the test instruments are shown in Table 11.

Table 10 Experimental reagent

Experimental reagent	Lot number	Manufacturer' s
			Aspirin enteric-coated tablet	2007803	Hunan Xinhui Pharmaceutical Co.,Ltd.
LIPOPOLYSACcharIDE(LPS)	L8880	BEIJING SOLARBIO TECHNOLOGY Co.,Ltd.
			Sodium pentobarbital	69020100	Shanghai chemical reagent Co., ltd
Physiological saline	D21051105B	SHANDONG KELUN PHARMACEUTICAL Co.,Ltd.

Table 11 laboratory apparatus

1.3 pharmaceutical formulation

Calculation of the gastric lavage dose of the rat: adults (70 kg) take two doses per day, with a daily dosage of 12g. According to the pharmacological experiment methodology (third edition), the ratio of human body surface area to experimental rat body surface area (200 g) is calculated to be 0.018, the daily gastric lavage clinical equivalent dose of each rat is 1.08g/kg (equivalent dose), and thus 1-fold (1.08 g/kg), 5-fold (5.4 g/kg) and 10-fold (10.8 g/kg) dose groups are set. Aspirin (calculated equivalent dose is 25.70mg/kg according to the pharmaceutical specification)

2. Experimental method

2.1 grouping of laboratory animals and model replication

Rats were randomly grouped into a placebo group, a model group, an aspirin group, a low dose group of chinese medicinal composition 1#, a medium dose group of chinese medicinal composition 1#, and a high dose group of chinese medicinal composition 1#, respectively.

Replication of LPS heating model, six hours before the experiment, fasted and water-free, rats were injected intraperitoneally with 100ug/kg of 10ug/mL LPS solution 2mL.

2.2 Experimental plans and general Condition records

The rectal temperature of the rats was measured twice daily for 1h for 4 consecutive days prior to molding. Rats with body temperature fluctuations (DeltaT > 0.5 ℃) and single body temperatures above 39 ℃ were knocked out. Rats in the traditional Chinese medicine composition 1# administration group and the aspirin administration group were respectively administrated by intragastric administration with corresponding medicines three consecutive days before molding, and physiological saline was administrated by the control group and the model group once daily. And (3) taking 1 rectal temperature measured in the first half hour of the molding as a basic temperature after the fasted food is not forbidden for 6 hours before the formal test, and taking the basic temperature as a blank control group, and carrying out LPS heating molding on the administration groups to establish an LPS heating model. After molding, the anal temperature of the rat is measured at 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h and 8h respectively, and recorded.

2.3 data analysis

Statistical analysis is carried out on the data obtained by experiments by using software such as Graphpad prism 8.0, excel 2020 and the like, the differences are analyzed and compared, and the experimental results are: average value.+ -. Standard deviation (S), P <0.05, has statistical significance. Significant differences between the two groups were considered at P < 0.05.

3. Experimental results

The body temperature change value (Δt) =body temperature of each period-base body temperature was calculated, the data was taken as ordinate, the time was taken as abscissa, and the time-dependent curve of each group of body temperature change values was plotted, and the result is shown in fig. 9.

As can be seen from the data in fig. 9, the body temperature rapidly increases from two hours after the model group is modeled for a large number of times, most rats are curled, auricles, lips and tails are scalded, most rats have the phenomenon of respiratory enhancement, and the peak value is reached for five hours and is significantly higher than that of the blank group, which indicates that the model is successfully copied.

The specific data of each group of body temperature are shown in Table 12.

Table 12 body temperature specification data for each group

Note that: p <0.05, < P <0.01, < P <0.001, < compared to the blank; compared to model group, #p <0.05, #p <0.01, #p <0.001; delta represents the difference between groups at the same dose.

The results showed that the aspirin group had a significant difference at 0.5h (P < 0.001), the low dose group had a significant difference at 0.5h (P < 0.01) but showed no significant antipyretic effect at high Wen Pingtai, the medium dose group had a significant difference at 0.5h (P < 0.01) but showed no significant antipyretic effect at high Wen Pingtai, and the high dose group had a sustained significant difference after 1h (P < 0.05) compared to the model group rats.

4. Analysis

The experiment adopts an LPS induction fever model, and LPS can stimulate macrophages after entering the body, transmit signals to generate a large amount of inflammatory mediators and attract neutrophils to gather. The LPS-induced fever model is similar to fever caused by clinically infectious inflammation, and belongs to a classical fever model.

In the experiment, a heating model is established by adopting LPS, and the anal temperature change of the rat after modeling is detected, so that the regulation effect of the traditional Chinese medicine composition 1# medication intervention on the heating model is judged. The result shows that the body temperature of the rats in the control group is normal; compared with the normal group, the body temperature of rats in the model group is obviously increased; compared with the model group, the aspirin group can effectively reduce the body temperature of the fever model group; compared with the model group, the medicine group can effectively reduce the body temperature at the peak of fever. The traditional Chinese medicine composition 1# can effectively inhibit the rise of the body temperature of a model rat with fever at a certain dosage, and reduce the body temperature of the rat at the peak of fever.

Example 4 experiment of Effect of traditional Chinese medicine composition 1# paraxylene on mouse auricle swelling

1. Materials and methods

1.1 laboratory animals

KM mice, SPF grade, 50, male and female halves, were purchased from Peking Vitrending laboratory animal Co., ltd. The feed is suitable for 7 days.

1.2 materials and instruments

One ten thousandth electronic balance, AR224CN, ohus instruments (constant state) limited; ear-beating device, ZH-YLS-Q4, yuanyang county Zhenhua teaching instrument Co., ltd; electric heating constant temperature water tank, CU-420, shanghai-Heng science instruments Co.

1.3 preparation of reagents and pharmaceutical preparations

Xylene, normal saline, sodium pentobarbital, aspirin enteric-coated tablet, and Chinese medicinal composition No. 1 (TFL). Calculation of the gastric lavage dose of the mice: adults (70 kg) take two doses per day, with a daily dosage of 12g. The amount of the drug in the stomach of each mouse was 1.56g/kg (equivalent dose) calculated according to the body surface area ratio of human to experimental mouse (20 g) of 0.0026 in the "pharmacological experiment methodology (third edition), and thus 1-fold dose (1.56 g/kg), 5-fold dose (7.8 g/kg) and 10-fold dose (15.6 g/kg) were set. Aspirin (calculated equivalent dose 200mg/kg according to the pharmaceutical instructions).

2. Experimental method

2.1 grouping of laboratory animals and model replication

The number of KM mice was 48, each male and female half, and randomly divided into 6 groups (8 per group): (1) control (control), model (2) (xylene), positive control (3) (aspirin, calculated equivalent dose 200mg/kg according to the drug instructions), equivalent dose 1-fold of 4-TFL (5.85 g/kg), 2-fold of 5-TFL (11.6 g/kg), 5-fold of 6-TFL (29.2 g/kg). Animal experiments were performed in a Shandong university of traditional Chinese medicine animal experiment center barrier environmental facility (laboratory animal use license number: SYXK 20170022). During the course of the experiment, all mice were free to receive diet and water with alternating illumination: 12h light/dark period. The experimental contents were approved by the animal ethics committee of Shandong university of traditional Chinese medicine (approval number: SDUTCM 20211015002).

Mice were housed adaptively for one week in a barrier environmental facility, numbered. The administration by gastric lavage is 1 time per 1 day for 7 consecutive days. 0.02ml of xylene is smeared on the front and back sides of the right ear of a mouse in a model group, an aspirin group, a high-dose group of the traditional Chinese medicine composition 1# and a medium-dose group of the traditional Chinese medicine composition 1# after the last administration for 1h to cause inflammation, so that auricle swelling of the mouse is induced, and physiological saline is smeared on the front and back sides of the right ear of a mouse in a control group. And (5) copying the auricle swelling model.

2.2 Experimental plans and general Condition records

After 1h, namely, after auricle swelling and modeling are successful, the cervical dislocation is killed, the ears are cut off immediately along the auricle baseline, holes are respectively punched at the same positions of the two ears by using a puncher with the diameter of 8mm, the two ears are precisely weighed on an electronic balance immediately, and the weight difference of the two ears is the swelling degree; the weight of the right ear-weight of the left ear/weight of the left ear is the swelling rate. The calculation formula is as follows:

swelling = right ear weight-left ear weight; swelling ratio (%) = (weight of right ear-weight of left ear)/weight of left ear×100%;

swelling inhibition (%) = (average swelling degree of blank group-average swelling degree of administration group)/average swelling rate of blank group×100%.

3. Experimental results

In the experimental result of the influence of the 1# paraxylene in the auricle swelling of the traditional Chinese medicine composition, the auricle swelling degree of the auricle one-time dose group (low dose) is observed to be higher than that of the aspirin enteric-coated tablet group, and the difference between the auricle swelling degree and the physiological saline group is obvious; as can be seen from punching and weighing calculation of auricle swelling inhibition rate, compared with physiological saline group, the low concentration and high concentration of the traditional Chinese medicine composition 1# have remarkable inhibition effect on auricle inflammation, and the medium-dose group effect is not obvious. The specific data are shown in Table 13.

TABLE 13 Effect of traditional Chinese medicine composition 1# paraxylene on mouse auricle swelling

Note that: * Comparison with the blank control group (1 p <0.01; # comparison with model group (2 p <0.05; ns has no statistical significance.

4. Analysis

The acute inflammation model of the auricle swelling of the mice caused by the dimethylbenzene is a common method in anti-inflammatory research, the method is simple and convenient to operate, is widely applied to pharmacodynamics research of anti-inflammatory medicaments, and according to the data in the table, the experiment proves that the traditional Chinese medicine composition 1# has good anti-inflammatory effect.

The foregoing is merely exemplary of the present application, and the scope of the present application is not limited to the specific embodiments, but is defined by the claims of the present application. Various modifications and changes may be made to the present application by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the technical ideas and principles of the present application should be included in the protection scope of the present application.

Claims

1. The traditional Chinese medicine composition for resisting influenza, relieving fever and diminishing inflammation is characterized by being prepared from the following raw materials in parts by weight: 12-60 parts of honeysuckle stem, 12-60 parts of dyers woad leaf, 12-60 parts of radix isatidis, 12-60 parts of dandelion, 3-15 parts of calyx seu fructus physalis and 3-15 parts of saussurea involucrata leaf.

2. The traditional Chinese medicine composition according to claim 1, wherein the weight ratio of honeysuckle stem, dyers woad leaf, radix isatidis, dandelion, calyx seu fructus physalis and sauropus pulvis is 4:4:4:4:1:1 in sequence.

3. The traditional Chinese medicine composition for resisting influenza, relieving fever and diminishing inflammation is characterized by being prepared from the following raw materials in parts by weight: 12-60 parts of honeysuckle stem, 12-60 parts of dyers woad leaf, 12-60 parts of radix isatidis, 12-60 parts of dandelion, 3-15 parts of calyx seu fructus physalis, 3-15 parts of saussurea involucrata, 0.2-0.4 part of maltodextrin and 0.1-0.5 part of stevioside.

4. A method of preparing the traditional Chinese medicine composition according to claim 3, comprising the steps of:

5. The preparation method according to claim 4, wherein the water adding amount in the step (1) is 12-16 times of the total amount of the Chinese medicinal materials in the step, and the water adding amount in the step (2) is 10-14 times of the total amount of the Chinese medicinal materials in the step.

6. The preparation method according to claim 4, wherein the soaking time in the step (1) is 0.2-1h, and the decocting time is 0.2-1h; the decoction time of the step (2) is 0.2-1h.

7. The method according to claim 4, wherein the third decoction is concentrated to a relative density of 1.09-1.11 in step (4).

8. The process of claim 4, wherein the drying in step (4) is spray drying, and the spray dried powder is granulated after passing through a 80-120 mesh sieve.

9. The use of a traditional Chinese medicine composition according to any one of claims 1-3 or a traditional Chinese medicine composition prepared by a preparation method according to any one of claims 4-8, characterized in that the traditional Chinese medicine composition is used for preparing anti-influenza, antipyretic and anti-inflammatory medicines.