Traditional Chinese medicine composition for treating fever and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating fever and application thereof, and belongs to the technical field of traditional Chinese medicine compositions. The traditional Chinese medicine composition for treating fever is prepared from the following raw materials in parts by weight: 7 to 11 parts of herba ephedrae, 7 to 11 parts of cassia twig, 10 to 14 parts of radix puerariae, 7 to 11 parts of apricot kernel, 7 to 11 parts of radix paeoniae alba, 2 to 4 parts of honey-fried licorice root, 7 to 11 parts of fresh ginger, 7 to 11 parts of fructus ziziphi jujubae, 10 to 14 parts of radix bupleuri, 7 to 11 parts of radix scutellariae, 5 to 7 parts of radix ginseng, 7 to 11 parts of rhizoma pinelliae preparata, 7 to 11 parts of rhizoma anemarrhenae and 25 to 35 parts of gypsum. The whole formula is reasonable in compatibility, clears heat and promotes salivation, treats both exterior and interior, and can be used for treating clinical fever diseases.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine compositions, and in particular relates to a traditional Chinese medicine composition for treating fever and application thereof. Background Art

[0002] Exogenous fever refers to the invasion of the body by the six evils of wind, cold, heat, dampness, dryness and fire or the epidemic air, which leads to the disharmony of the body's nutrition and defense, imbalance of yin and yang of the internal organs, and the appearance of a type of disease with fever as a clinical symptom. Exogenous fever is equivalent to a variety of infectious diseases in modern medicine, and fever is its main symptom. Although increased body temperature is conducive to controlling infection, long-term high fever can also cause damage to the respiratory, circulatory and nervous systems. At present, the treatment of exogenous fever is mainly based on anti-infection, antiviral and antipyretic. The fever is reduced quickly, but the body temperature is prone to recurrence after stopping the drug, and it will produce electrolyte disorders, liver and kidney damage, low body defense function and gastrointestinal ulcers and other toxic side effects.

[0003] Under the guidance of syndrome differentiation and treatment and holistic concept, traditional Chinese medicine uses internal and external treatment methods to treat exogenous fever with definite efficacy and few adverse reactions, and plays a huge role in the prevention and treatment of infectious diseases. Traditional Chinese medicine has its own unique syndrome differentiation and treatment system in the treatment of exogenous fever. Therefore, it is of positive significance to provide a traditional Chinese medicine that can effectively treat exogenous fever. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a Chinese medicine composition for treating fever, which can effectively treat exogenous wind-heat.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] A traditional Chinese medicine composition for treating fever comprises the following raw materials in parts by weight: 7-11 parts of ephedra, 7-11 parts of cassia twig, 10-14 parts of kudzu root, 7-11 parts of apricot kernel, 7-11 parts of white peony root, 2-4 parts of roasted liquorice root, 7-11 parts of ginger, 7-11 parts of jujube, 10-14 parts of bupleurum, 7-11 parts of scutellaria, 5-7 parts of ginseng, 7-11 parts of pinellia tuber, 7-11 parts of anemarrhena, and 25-35 parts of gypsum.

[0007] Preferably, the raw materials are included in parts by weight: 8-10 parts of ephedra, 8-10 parts of cinnamon twig, 11-13 parts of kudzu root, 8-10 parts of apricot kernel, 8-10 parts of white peony root, 2.5-3.5 parts of roasted licorice root, 8-10 parts of ginger, 8-10 parts of jujube, 11-13 parts of bupleurum, 8-10 parts of scutellaria, 5.5-6.5 parts of ginseng, 8-10 parts of pinellia, 8-10 parts of anemarrhena, and 28-32 parts of gypsum.

[0008] Preferably, the raw materials are included in parts by weight: 9 parts of ephedra, 9 parts of cinnamon twig, 12 parts of kudzu root, 9 parts of apricot kernel, 9 parts of white peony root, 3 parts of roasted licorice root, 9 parts of ginger, 9 parts of jujube, 12 parts of bupleurum, 9 parts of scutellaria, 6 parts of ginseng, 9 parts of pinellia, 9 parts of anemarrhena, and 30 parts of gypsum.

[0009] Another object of the present invention is to provide the use of the traditional Chinese medicine composition in the preparation of a medicine for treating fever.

[0010] Preferably, the fever is exogenous fever.

[0011] Preferably, the exogenous fever includes fever caused by any one of respiratory infectious diseases, viral encephalitis, influenza and lobar pneumonia.

[0012] Preferably, the drug for treating fever reduces either or both of the white blood cell count and the neutrophil count, and increases the lymphocyte count.

[0013] Preferably, the drug for treating fever exerts a cooling effect via the TLR4 / NF-κB / COX2 signaling pathway.

[0014] Another object of the present invention is to provide a medicine for treating fever, wherein the medicine contains 0.1-100wt% of the traditional Chinese medicine composition.

[0015] Preferably, the medicament comprises pharmaceutically acceptable excipients.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The invention provides a Chinese medicine composition for treating fever, wherein ephedra, gypsum, bupleurum and kudzu root, which have the effects of sweating, penetrating muscles and relieving exterior symptoms, warming and dispersing cold, soothing the liver and relieving depression, and promoting fluid production and quenching thirst, are used as the main medicines; cinnamon twig, white peony root, scutellaria baicalensis and rhizome of anemarrhena, which have the effects of stopping sweating, relieving pain, purging fire and detoxifying, and nourishing yin and moistening dryness, are used as the assistant medicines; apricot kernel, ginseng, pinellia tuber, ginger and jujube, which can relieve cough and resolve phlegm, nourish yin and promote fluid production, are used as the adjuvant medicines; and licorice root is used as the guiding medicine for harmonizing the various medicines. The whole formula can clear away heat and promote fluid production, treat both the exterior and the interior, and can effectively treat exogenous wind-heat. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 : Relative expression of cytokine mRNA before and after treatment, Note: Inter-group comparison, #P<0.05, ##P<0.01, ###P<0.001; Intra-group comparison, *P<0.05, **P<0.01, ***P<0.001;

[0019] Figure 2: Relative mRNA expression of key genes in the TLR4 pathway before and after treatment, Note: Inter-group comparison, #P<0.05, ##P<0.01, ###P<0.001; Intra-group comparison, *P<0.05, **P<0.01, ***P<0.001;

[0020] Figure 3 : Pathological images of hypothalamus tissues of rats in each group (HE staining, ×400);

[0021] Figure 4 : Immunohistochemistry of hypothalamus tissue in rats with LPS-induced fever (×400);

[0022] Figure 5 : Quantitative analysis results of immunohistochemistry;

[0023] Figure 6 :Levels of serum inflammatory factors in rats with LPS-induced fever;

[0024] Figure 7 :The expression of cytokine mRNA in rats induced by LPS fever, Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; Compared with the model group, *P<0.05, **P<0.01, ***P<0.001;

[0025] Figure 8 :The mRNA expression of genes related to TLR4 / NF-κB / COX2 signaling pathway in rats with LPS-induced fever. Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; Compared with the model group, *P<0.05, **P<0.01, ***P<0.001;

[0026] Fig. 9 :Expression of key target proteins of TLR4 / NF-κB / COX2 signaling pathway in rats with LPS-induced fever: Western blot;

[0027] Fig.10 :Expression of key target proteins in TLR4 / NF-κB / COX2 signaling pathway in rats with LPS-induced fever: grayscale value comparison of target proteins and internal reference;

[0028] Fig.11 : Pathological images of hypothalamus tissues of rats in each group (HE staining, ×400);

[0029] Fig.12 : Immunohistochemistry of hypothalamus tissue in rats induced by dry yeast fever (×400);

[0030] Fig.13 : Quantitative analysis results of immunohistochemistry;

[0031] Fig.14 : Levels of serum inflammatory factors in rats induced by dry yeast fever;

[0032] Fig.15 : Expression of cytokine mRNA in rats induced by dry yeast, Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; Compared with the model group, *P<0.05, **P<0.01, ***P<0.001;

[0033] Fig.16 :The mRNA expression of genes related to TLR4 / NF-κB / COX2 signaling pathway in rats with dry yeast-induced fever. Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001;

[0034] Fig.17 :Expression of key target proteins of TLR4 / NF-κB / COX2 signaling pathway in rats induced by dry yeast fever: Western blot;

[0035] Fig.18 :Expression of key target proteins in TLR4 / NF-κB / COX2 signaling pathway in rats induced by dry yeast fever: gray value comparison of target protein and internal reference. DETAILED DESCRIPTION

[0036] The invention provides a traditional Chinese medicine composition for treating fever. The composition comprises the following raw materials in parts by weight: 7-11 parts of ephedra, 7-11 parts of cassia twig, 10-14 parts of kudzu root, 7-11 parts of apricot kernel, 7-11 parts of white peony root, 2-4 parts of roasted liquorice root, 7-11 parts of ginger, 7-11 parts of jujube, 10-14 parts of bupleurum, 7-11 parts of scutellaria, 5-7 parts of ginseng, 7-11 parts of pinellia tuber, 7-11 parts of anemarrhena and 25-35 parts of gypsum. Preferably, the following raw materials in parts by weight are included: 8-10 parts of ephedra, 8-10 parts of cassia twig, 11-13 parts of kudzu root, 8-10 parts of almond, 8-10 parts of white peony root, 2.5-3.5 parts of licorice root, 8-10 parts of ginger, 8-10 parts of jujube, 11-13 parts of bupleurum, 8-10 parts of scutellaria, 5.5-6.5 parts of ginseng, 8-10 parts of pinellia tuber, 8-10 parts of rhizoma anemarrhenae, 28-32 parts of gypsum. More preferably, the following raw materials in parts by weight are included: 9 parts of ephedra, 9 parts of cassia twig, 12 parts of kudzu root, 9 parts of almond, 9 parts of white peony root, 3 parts of licorice root, 9 parts of ginger, 9 parts of jujube, 12 parts of bupleurum, 9 parts of scutellaria, 6 parts of ginseng, 9 parts of pinellia tuber, 9 parts of rhizoma anemarrhenae, 30 parts of gypsum. The raw materials described in the present invention are all commercially available commodities well known to those skilled in the art.

[0037] In the present invention, the ephedra is pungent and slightly bitter in taste, warm in nature, and enters the lung and bladder meridians. It is good at opening and dispersing lung qi, sweating and relieving the exterior symptoms, relieving asthma, promoting diuresis and reducing swelling, warming and dispersing cold, relieving numbness and dispersing stagnation, and has strong dispersing ability and good asthma-relieving effect; the gypsum is sweet and pungent in taste, very cold in nature, enters the lung and stomach meridians, mainly clears and releases qi, and also penetrates and resolves. It is good at clearing and releasing qi heat and lung and stomach fire, and can also relieve muscle and penetrate heat. When the heat is removed, restlessness is eliminated, body fluid is generated, and thirst is stopped; the bupleurum is pungent and bitter in taste, slightly cold in nature, and enters the liver, gallbladder, and lung meridians. Bupleurum is bitter, purging, pungent and dispersing, aromatic and soaring, slightly cold and can clear, and can disperse the evil qi in the gallbladder meridian and resolve and reduce fever. It also disperses the stagnant Qi in the liver and gallbladder meridians and relieves the liver and depression, and also raises the clear Yang Qi of the liver and gallbladder and lifts the sunken; the Pueraria root is sweet and pungent in taste, and has a strong nature. It enters the spleen, stomach, and lung meridians. The Pueraria root is sweet and pungent, lightly lifts and disperses, is mild and slightly cool and can clear, and can penetrate and relieve wind-heat on the surface of the muscles, relieve muscles and reduce fever, and release exterior, and release rashes, and also encourages the clear Yang of the spleen and stomach to rise and produce fluid to quench thirst, and raise Yang to stop diarrhea; the ephedra, gypsum, bupleurum and Pueraria root are used together, which has the effects of sweating, penetrating muscles to relieve exterior, warming and dispersing cold, soothing the liver and relieving depression, and producing fluid to quench thirst. The four are coordinated and compatible, and as the main medicine, they play a leading role in the prescription for the symptoms.

[0038] In the present invention, the cinnamon twig is pungent and sweet, warm in nature, and enters the heart, lung, and bladder meridians. The cinnamon twig is pungent, dispersing, warming, and unblocking, sweet and warm to help yang, warming and unblocking, smoothing and moistening the yang of the whole body, and smoothing the blood vessels of the whole body. It is good at dispersing wind and cold and relieving wind and cold or wind evil on the surface, and is good at warming and unblocking yang, dispersing cold evil, unblocking blood vessels, promoting chest yang, warming and transforming water and dampness, and relieving pain; the white peony root is bitter and sour, slightly cold in nature, and enters the liver and spleen meridians, and has the effects of nourishing blood and regulating menstruation, restraining yin and stopping sweating, softening the liver and relieving pain, and suppressing liver yang; the scutellaria baicalensis is bitter and cold in nature, and enters the lungs, gallbladder, spleen, large intestine, In the small intestine meridian, Scutellaria baicalensis is bitter, cold, clearing and drying, and has the functions of clearing heat and dampness, purging fire and detoxifying, stopping bleeding, and calming the fetus; the Anemarrhena asphodeloides is bitter and sweet, and is cold in nature, and enters the lung, stomach, and kidney meridians. The Anemarrhena asphodeloides is bitter, purging cold and clearing, and is sweet, moistening and slippery. It can clear lung heat and purge fire, clear stomach heat and eliminate thirst, and nourish kidney yin and moisten the intestines and relieve deficiency heat; the cinnamon twig, white peony root, scutellaria baicalensis and Anemarrhena asphodeloides are used together as the minister drugs in the formula to assist the monarch drugs in exerting their effects, and make the whole formula boost yang and smooth blood circulation, stop sweating, relieve pain, purge fire and detoxify, nourish yin and moisten dryness, treat both the exterior and the interior, and are suitable for both deficiency and excess.

[0039] In the present invention, the almond is bitter almond, bitter in taste, slightly warm in nature, enters the lung and large intestine meridians, and has the effects of relieving cough and relieving asthma, moistening the intestines and promoting bowel movements; the ginseng is sweet, slightly bitter, slightly warm in nature, and enters the spleen, lung, heart, and kidney meridians. Ginseng is sweet, slightly warm, slightly bitter and not diuretic, and is good at greatly replenishing vital energy, treating qi deficiency and impotence, and is good at replenishing the qi of the spleen and lungs, treating various symptoms of spleen and lung qi deficiency, and also replenishing qi to produce body fluid, calm the mind, and improve intelligence, and treating thirst due to body fluid loss, polydipsia, restlessness, palpitations and forgetfulness; the clear pinellia is a processed product of pinellia, which is made by boiling pinellia with 8% alum water, and has the effect of drying dampness. The ginger is pungent in taste and slightly warm in nature, and enters the lung, spleen and stomach meridians, and has the effects of dispelling cold, warming the middle and stopping vomiting, warming the lung and stopping cough, and detoxifying; the jujube is sweet in taste and warm in nature, and enters the spleen and stomach meridians, and has the effects of tonifying the spleen and stomach, replenishing qi and promoting body fluid, regulating the Ying and Wei, and detoxifying. It is mainly used to treat stomach deficiency, poor appetite, weak spleen and loose stools, insufficient qi, blood and body fluid, disharmony between the Ying and Wei, palpitations, and restlessness in women; the almonds, ginseng, pinellia, ginger and jujube can relieve cough and resolve phlegm, nourish yin and promote body fluid, and assist the main medicine and the minister medicine to play the effects of clearing away heat and promoting body fluid, and are adjuvants in the formula.

[0040] In the present invention, the roasted licorice root is a processed product of licorice root. The roasted licorice root is sweet, neutral in nature, and enters the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and stomach, invigorating qi and restoring pulse. The roasted licorice root can reconcile various medicines and make the various medicines in the prescription coordinated and compatible, and is the guiding medicine of the prescription.

[0041] The whole prescription of the invention has reasonable compatibility, clears away heat and promotes the production of body fluid, treats both the exterior and the interior, and can effectively treat exogenous wind-heat.

[0042] The present invention also provides the use of the traditional Chinese medicine composition in preparing a medicine for treating fever, wherein the fever is exogenous fever; the exogenous fever includes fever caused by any one of respiratory infectious diseases, viral encephalitis, influenza and lobar pneumonia.

[0043] The Chinese medicine composition provided by the present invention can be widely used in clinical exogenous febrile diseases and has a good antipyretic effect. The medicine for treating fever prepared by the present invention can reduce any one or more of the white blood cell count and the neutrophil count, and increase the lymphocyte count. The medicine provided by the present invention can effectively improve the blood indexes of patients with fever.

[0044] Preferably, the drug exerts a cooling effect through the TLR4 / NF-κB / COX2 signaling pathway. The drug provided by the present invention can significantly reduce the expression levels of TLR4, MyD88, NFκB p65, COX2, TRAF6, IL-1β, IL6, TNF-α, and IFN-α in patients, and exerts a therapeutic effect on exogenous fever through the TLR4 / NF-κB / COX2 signaling pathway.

[0045] The present invention also provides a medicine for treating fever, the medicine containing 0.1-100wt% of the Chinese medicine composition. The medicine of the present invention also includes pharmaceutically acceptable excipients, and the present invention does not limit the specific excipients.

[0046] In a specific embodiment of the present invention, the Chinese medicine composition is prepared as granules, comprising the following steps: weighing each Chinese medicine in proportion, preparing each Chinese medicine into Chinese patent medicine granules, and mixing each Chinese patent medicine granule to obtain the granules of the Chinese medicine composition of the present invention. The preparation of the granules described in the present invention complies with the technical requirements of the "Notice of the State Food and Drug Administration on the Issuance of the "Technical Requirements for Quality Control and Standardization of Chinese Medicine Formula Granules" (No. 16, 2021)". The manufacturer of the Chinese patent medicine granules described in the present invention is Zhongjing Wanxi Pharmaceutical Co., Ltd.

[0047] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0048] Example 1

[0049] A traditional Chinese medicine composition for treating fever comprises the following raw materials in parts by weight: 9 parts of ephedra, 9 parts of cassia twig, 12 parts of kudzu root, 9 parts of apricot kernel, 9 parts of white peony root, 3 parts of roasted liquorice root, 9 parts of ginger, 9 parts of jujube, 12 parts of bupleurum, 9 parts of scutellaria, 6 parts of ginseng, 9 parts of pinellia tuber, 9 parts of anemarrhena, and 30 parts of gypsum.

[0050] Example 2

[0051] A traditional Chinese medicine composition for treating fever comprises the following raw materials in parts by weight: 8 parts of ephedra, 10 parts of cassia twig, 11 parts of kudzu root, 8 parts of apricot kernel, 10 parts of white peony root, 3 parts of roasted liquorice root, 10 parts of ginger, 8 parts of jujube, 13 parts of bupleurum, 8 parts of scutellaria, 6 parts of ginseng, 10 parts of pinellia tuber, 8 parts of anemarrhena, and 32 parts of gypsum.

[0052] Example 3

[0053] A traditional Chinese medicine composition for treating fever comprises the following raw materials in parts by weight: 7 parts of ephedra, 11 parts of cassia twig, 14 parts of kudzu root, 7 parts of apricot kernel, 7 parts of white peony root, 4 parts of roasted liquorice root, 11 parts of ginger, 7 parts of jujube, 10 parts of bupleurum, 7 parts of scutellaria, 5 parts of ginseng, 11 parts of pinellia, 7 parts of anemarrhena, and 27 parts of gypsum.

[0054] Comparative Example 1

[0055] Yinhuang Granules (National Medicine Approval No. Z20023005, Jiangxi Jimin Kexin Pharmaceutical Co., Ltd.), the raw materials are: honeysuckle extract and scutellaria baicalensis extract.

[0056] Test Example 1

[0057] Clinical effects of different Chinese herbal compound prescriptions on patients with exogenous fever.

[0058] 1.1 Clinical case collection

[0059] Patients with exogenous fever (three-yang combined syndrome) were collected in the fever clinic of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. They signed informed consent and were divided into an experimental group and a control group with a ratio of 2:1, with 72 cases in the experimental group and 36 cases in the control group.

[0060] 1.1.1 Diagnostic criteria

[0061] 1) Diagnostic criteria for acute upper respiratory tract infection

[0062] Refer to "Internal Medicine" (9th edition) and "Guidelines for Primary Diagnosis and Treatment of Acute Upper Respiratory Tract Infection" (2018).

[0063] (1) Acute onset, with respiratory symptoms such as nasal congestion, runny nose, dry throat, etc., and may be accompanied by systemic symptoms such as fever, chills, headache, limb aches and discomfort;

[0064] (2) In viral infections, the white blood cell count is normal or low and the lymphocyte ratio is increased. In bacterial infections, the white blood cell count and neutrophil ratio are increased.

[0065] 2) Diagnostic criteria for exogenous fever (three yang combined syndrome)

[0066] Refer to the Ming Dynasty Zhao Kaimei edition of "Treatise on Febrile Diseases", "Six Books on Febrile Diseases", and "TCM Clinical Diagnosis and Treatment Terminology - Syndrome Part" (revised edition).

[0067] (1) Main symptoms: fever, chills, thirst, and dry throat;

[0068] (2) Secondary symptoms: headache, nasal congestion, runny nose, body pain, bitter taste in the mouth, sweating, dry nose, irritability, eye socket pain;

[0069] (3) Tongue and pulse: Pale tongue, thin yellow fur, and floating and strong pulse.

[0070] Judgment criteria: meet the above 3 main symptoms (one of which is fever) + 3 secondary symptoms combined with tongue and pulse.

[0071] 1.1.2 Inclusion criteria

[0072] Refer to "Guidelines for Clinical Research of New Chinese Medicines" (2002 edition).

[0073] 1) Meet the diagnostic criteria of Western medicine for acute upper respiratory tract infection;

[0074] 2) Meet the diagnostic criteria of exogenous fever (three yang combined syndrome) in traditional Chinese medicine;

[0075] 3) The duration of fever is within 48 hours;

[0076] 4) Patients aged between 18 and 75 years, regardless of gender;

[0077] 5) The patients and their families were informed of the survey and signed the informed consent.

[0078] 1.1.3 Exclusion criteria

[0079] 1) Patients with other lung diseases such as asthma, chronic bronchitis, bronchiectasis, etc.

[0080] 2) Patients who also suffer from serious underlying diseases such as cardiovascular, liver, kidney, respiratory system, mental illness or communication disorders;

[0081] 3) Patients during pregnancy and lactation;

[0082] 4) Patients with allergic reactions to the drugs used in this study;

[0083] 5) Other circumstances determined by the researchers to be unsuitable for participating in the trial.

[0084] 1.1.4 Clinical medication

[0085] Test group: Take the Chinese medicine composition provided in Example 1 (recorded as Magui Chai Shi Fang): 9g of Ephedra, 9g of Cinnamon Twig, 12g of Puerariae Radix, 9g of Apricot Kernel, 9g of White Peony Root, 3g of Radix Glycyrrhizae Preparata, 9g of Ginger, 9g of Jujube, 12g of Bupleurum, 9g of Scutellariae Radix, 6g of Ginseng, 9g of Pinellia Rhizoma, 9g of Rhizoma Anemarrhenae, 30g of Gypsum; After calculation, the dosage of the granules of Example 1 is: 1.8g of Ephedra, 1.5g of Cinnamon Twig, 4.8g of Puerariae Radix, 0.9g of Apricot Kernel, 2g of White Peony Root, 1.5g of Radix Glycyrrhizae Preparata, 0.7g of Ginger, 7.5g of Jujube, 3g of Bupleurum, 4.1g of Scutellariae Radix, 2.4g of Ginseng, 1.5g of Pinellia Rhizoma, 5g of Rhizoma Anemarrhenae, 0.5g of Gypsum. Method of taking: 1 pack each time, 2 times a day, take with 200mL of boiled water, and use for 3 consecutive days.

[0086] Control group: Take the Yinhuang granules provided in comparative example 1: National medicine standard Z20023005, Jiangxi Jimin Kexin Pharmaceutical Co., Ltd. Dosage: 2 bags each time, 2 times a day, take with boiled water, for 3 consecutive days.

[0087] 1.1.5 Collection of clinical blood samples

[0088] At two points before and after medication, 5 mL of non-anticoagulated blood and 20 mL of EDTA anticoagulated blood were collected from the observation group using a disposable blood collection needle. Blood samples from the control group were collected at the same time as those from the observation group.

[0089] 1.1.6 Information Collection

[0090] A case observation form was prepared to collect basic information, physical examination, and four diagnostic tests of traditional Chinese medicine of the two groups of clinical subjects. The blood routine indexes of the observation group were tested.

[0091] General information: includes basic information, personal history, past medical history, marital history, allergies and medication history.

[0092] Four diagnostic information: tongue condition, pulse condition, symptoms, physical signs, etc.

[0093] The fully automated biochemical analyzer was used to detect the blood routine of the subjects.

[0094] 1) The quantification table for grading exogenous fever symptoms is shown in Table 1.

[0095] Table 1 Grading and quantification table of exogenous fever symptoms

[0096] Main symptoms None (0 points) Light (2 points) Medium (4 points) Heavy (6 points) fever ＜37.3℃ Body temperature 37.3-37.9℃ Body temperature 38.0-38.5℃ Body temperature 38.6℃-39℃ Chills none No need to add clothes when you feel cold Wear more clothes if you feel cold Chills require thicker clothing or bedding Thirsty none Slight thirst Thirsty Very thirsty Dry throat none Slightly dry throat Obvious dry throat Sore throat secondary symptoms None (0 points) Light (1 point) Medium (2 points) Heavy (3 points) Headache none Mild headache that comes and goes Severe headache that lasts for a long time I have a severe headache and cannot work. Sweating none Slight sweating Sweating Excessive sweating Bitter taste in mouth none Mild bitter taste Bitter taste in mouth Obvious bitter taste in the mouth Dry nose none Slightly dry nose Obvious dry nose Dry nose with blood Orbital pain none Mild pain Orbital pain Significant pain Body pain none Mild body pain Obvious body pain Persistent body pain Nasal congestion none Blockage, heavy sound Occasional nasal congestion Persistent nasal congestion Runny nose none Occasionally runny nose A small amount of turbid mucus Continuous runny nose, heavy Upset none A little upset Upset Disturbed

[0097] 1.1.7 Case dropout and treatment

[0098] All qualified subjects who withdraw from the trial at any time and for any reason, as long as they do not complete the observation period specified in the protocol, except for those who stop taking the drug before the end of the treatment course due to symptom disappearance, are considered dropouts.

[0099] Treatment of cases who drop out of the trial midway or are lost to follow-up:

[0100] (1) Researchers should take active measures, such as making appointments in person, by phone, or by letter, to contact the subjects as much as possible to inquire about the reasons, record the last time they took the medication, and complete the last test as much as possible.

[0101] (2) For cases in which the subjects withdraw from the trial due to allergic reactions or adverse reactions, the researchers should actively take appropriate treatment measures based on the actual situation of the subjects.

[0102] (3) For all cases of dropout, the trial conclusion form and the reason for dropout should be filled in the clinical observation form. The statistical analysis of dropout cases should be handled in accordance with the actual situation. For example, those who have adverse reactions should be included in the statistics of adverse reactions; those who cannot complete the entire course of treatment are considered dropouts. There is no need to fill in the dropout patients separately. For all dropout cases, the research case record form and other materials should be summarized and statistically analyzed.

[0103] 1.2 Data Management

[0104] Each observer should carefully and truthfully fill in the "Clinical Efficacy Evaluation Study Case Observation Form for the Treatment of Exogenous Fever (Three Yang Combination Syndrome) with Ma Gui Chai Shi Fang", and the data should not be changed at will, and there should be no blank items. If the writing error needs to be modified, the modification date should be noted and signed. After all case observations are completed, another two people will enter and verify the data, and enter the data into an Excel table to establish a database for subsequent data statistical processing.

[0105] 1.3 Statistical analysis

[0106] 1.3.1 Statistical analysis data set

[0107] Per-Protocol population (PP) was used to perform statistical analysis on all observation units and their observed values ​​that met the trial protocol and completed the analysis.

[0108] 1.3.2 Statistical analysis software

[0109] SPSS26.0 software was used for statistical analysis.

[0110] 1.4.3 Statistical analysis methods

[0111] Test level: All statistical tests were two-sided, with α = 0.05 level and P ≤ 0.05 being statistically significant;

[0112] Baseline data: Demographic data were described using line tables;

[0113] Statistical description: If the numerical variable follows a normal distribution, the mean ± standard deviation is used. If it does not obey the normal distribution, it is represented by the median (interquartile range) M(Q). The categorical variables are described statistically using frequency (composition ratio);

[0114] Treatment of missing values: If the missing values ​​of a subject exceed 20%, it will be treated as a failure. If the missing values ​​are less than 20% of the total cases, the missing values ​​will be replaced by the average value of the series data;

[0115] Parameter estimation: Parameter estimation was performed using 95% CI;

[0116] Effectiveness analysis: The frequency of symptoms and signs, symptom scores, etc. at different time points before and after treatment in the two groups were analyzed by variance analysis, and the corresponding statistical results were selected according to the results of the sphericity test; the paired t-test was used for the comparison before and after within the group if it was in line with the normal distribution, and the Wilcoxon signed rank test was used if it could not be converted to normal.

[0117] Safety analysis: Describe the adverse events that occurred in this trial and the changes in laboratory test results before and after the trial.

[0118] 1.5 Experimental Results

[0119] 1.5.1 Analysis of baseline data of selected cases

[0120] The patients were mainly from the Fever Clinic of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. After the observation, 2 patients dropped out of the control group, and 34 patients were actually completed; 3 patients dropped out of the experimental group, and 69 patients were actually completed. A total of 103 patients were included. The patient information is shown in Table 2-4.

[0121] Table 2 Comparison of gender between the two groups of patients [number of cases (percentage %)]

[0122]

[0123] Table 3 Age distribution of patients in the two groups [number of cases (percentage %)]

[0124]

[0125] Table 4 Comparison of the severity of the disease between the two groups [number of cases (percentage %)]

[0126]

[0127] As shown in Tables 2 to 4, there was no statistically significant difference in gender, age, and disease severity between the control group and the experimental group.

[0128] 1.5.2 Analysis of clinical data of selected cases

[0129] Table 5 Comparison of body temperature between the two groups before and after treatment [M(Q)]

[0130]

[0131] Note: Compared with the control group before medication, *P<0.05, **P<0.01, ***P<0.001; compared with the experimental group before medication, #P<0.05, ##P<0.01, ###P<0.001.

[0132] As shown in Table 5, the patient's body temperature dropped significantly 0.5 hours after taking the Chinese medicine composition of the present invention, and the body temperature stabilized at normal temperature after 12:00 on the second day of medication. The body temperature of the control group dropped to a significant level after 12:00 on the second day of medication, and the body temperature recurred subsequently.

[0133] Table 6 Comparison of fever reduction time between the two groups of patients [M(Q)]

[0134] Group Onset time (h) Time to first drop to normal level (h) Complete cooling time (h) Control group 28.00(4.00) 36.00(16.00) 52.00(4.00) Experimental Group 8.00(6.00) 24.00(13.00) 24.00(8.00) Z -6.971 -6.043 -5.716 P <0.001 <0.001 <0.001

[0135] As shown in Table 6, the Chinese medicine provided by the present invention takes effect faster than the control group, and the time taken for the body temperature to drop to normal temperature and the time taken for the fever to subside completely are both shorter.

[0136] Table 7 Comparison of cooling efficacy between the two groups of patients [number of cases (percentage %)]

[0137]

[0138] As shown in Table 7, the total effective rate of the Chinese medicine composition of the present invention is 95.65%, which is significantly higher than 82.35% of the control group.

[0139] 1.5.3 Clinical symptom score analysis

[0140] The TCM syndrome score includes three aspects: main symptom score, secondary symptom score and total score. The main symptoms include fever, aversion to cold, dry throat and thirst, and the secondary symptoms include headache, nasal congestion, runny nose, body pain, sweating, dry nose, irritability, bitter mouth and orbital pain. The results are shown in Tables 8 to 10.

[0141] Table 8 Comparison of TCM main symptom scores between the two groups [M(Q)]

[0142]

[0143] Table 9 Comparison of TCM secondary symptom scores between the two groups [M(Q)]

[0144]

[0145] Table 10 Comparison of total TCM syndrome scores between the two groups [M(Q)]

[0146]

[0147]

[0148] According to Tables 8 to 10, by comparing the symptom scores before and after treatment, the results show that Ma Gui Chai Shi Fang can effectively alleviate the symptoms of patients with exogenous fever.

[0149] 1.5.4 Blood routine analysis results

[0150] Table 11 Comparison of WBC between the two groups before and after treatment

[0151]

[0152] In the inter-group comparison, there was no significant statistical difference in the white blood cell count (WBC), lymphocyte count (L) and neutrophil count (N) levels between the control group and the experimental group before treatment (P>0.05), indicating that the levels of these indicators in the two groups were similar before treatment. After treatment, there were significant statistical differences in the levels of WBC and N between the control group and the experimental group (P<0.01), while the difference in the level of L was still not significant (P>0.05). In the intra-group comparison, compared with before treatment, the levels of WBC, L and N in the control group did not change significantly after treatment (P>0.05). After treatment, the levels of WBC and N in the experimental group were significantly reduced, and the level of L was significantly increased, with extremely significant statistical differences (P<0.001), indicating that the experimental group achieved significant results in improving blood indicators.

[0153] 1.5.5 Cytokine concentration test results

[0154] Table 12 Comparison of inflammatory factors between the two groups before and after treatment

[0155]

[0156] 1.5.6 Cytokine mRNA detection results

[0157] Table 13 Comparison of cytokine mRNA expression before and after treatment between the two groups

[0158]

[0159]

[0160] Table 14 Comparison of mRNA expression of key genes in the TLR4 pathway between the two treatment groups

[0161]

[0162] According to Table 12-Table 14 and Figure 1-Figure 2 It can be seen that the levels of IL-1β, IL6, TNF-α, IFN-α, and CRP in both groups after treatment were significantly lower than those before treatment, indicating that the Chinese medicine composition and Yinhuang granules provided by the present invention can reduce the levels of inflammatory factors in patients with exogenous fever. The expression of genes TLR4, MyD88, NFκB p65, COX2, TRAF6, IL-1β, IL6, TNF-α, and IFN-α in the Chinese medicine composition of the present invention after treatment was significantly reduced compared with before treatment, and the expression of genes NFκBp65, IL6, and TNF-α in the Yinhuang granules group after treatment was significantly reduced compared with before treatment, indicating that the Chinese medicine composition provided by the present invention plays a role in treating exogenous fever through the TLR4 / NF-κB / COX2 signaling pathway.

[0163] Test Example 2

[0164] Study on the antipyretic mechanism of the Chinese medicine composition of the present invention on LPS-induced fever rats

[0165] 2.1 Animal experiments

[0166] An LPS-induced rat fever model was adopted, and different concentrations of the Chinese medicine composition provided in Example 1 of the present invention (granules, the specific dose is the same as in Test Example 1, recorded as Ma Gui Chai Shi Fang) were administered by gavage, and the rat rectal temperature and the expression levels of inflammatory indicators in serum and hypothalamus tissue were measured to investigate the antipyretic effect of Ma Gui Chai Shi Fang on the LPS-induced rat fever model; real-time fluorescence quantitative PCR technology and protein immunoblotting (Western Blotting) were used to detect the effect of Ma Gui Chai Shi Fang on the expression of related genes / proteins in the TLR4 / NF-κB / COX2 signaling pathway of LPS-induced fever rats.

[0167] 2.2 Construction and grouping of fever animal models

[0168] After SD rats were fed adaptively for one week, their rectal temperature was measured twice a day for 3 consecutive days. Before measuring the rectal temperature, the rats were allowed to empty their feces, and tape was wrapped at 3 cm at the end of the thermometer to keep the insertion depth consistent. The reading was recorded after the beep was heard. The rats were adapted to the operation, and the animals with a single body temperature exceeding 38°C and a temperature difference of more than 0.5°C between two consecutive measurements were eliminated. 72 rats that met the experimental requirements were selected. They were randomly divided into a blank group, a model group, an aspirin group (100 mg / kg), and a low (7.44 g / kg), medium (14.88 g / kg), and high-dose groups (29.76 g / kg) of Magui Chai Shi Fang, with 12 rats in each group, and each group was recorded as a blank group, a LPS model group, an ASP group, a low-dose MGCS group, a medium-dose MGCS group, and a high-dose MGCS group. According to the grouping, the blank group and the model group were given an equal volume of normal saline for 3 consecutive days. On the third day, all rats were fasted but not watered for 12 hours. Before the formal start of the experiment, the body temperature was measured once every 30 minutes, and the average value of three consecutive measurements was taken as the basal body temperature. Then the last drug was administered, and 30 minutes later, except for the blank group, all other groups were intraperitoneally injected with 80 μg / kg LPS to establish a fever model. After modeling, the rectal temperature was measured every 1 hour for a total of 6 hours, and the temperature change value was calculated.

[0169] 2.3 Observation indicators

[0170] 2.3.1 Behavioral indicators

[0171] Observe the rats for shivering, diarrhea, lethargy, drowsiness, and piloerection, and observe changes in skin color of the extremities.

[0172] 2.3.2 Body temperature

[0173] 1) Observe the changes in body temperature of rats in different drug groups and calculate the maximum temperature rise (ΔTmax): the maximum temperature rise minus the basal body temperature.

[0174] 2) 6-hour temperature response index (TRI6): Taking the basal body temperature of rats as the baseline, the body temperature value as the vertical axis (each 1°C corresponds to 1 cm), and the time value as the horizontal axis (each 1 hour corresponds to 1 cm), the body temperature change values ​​at each time point are plotted into a temperature change curve. The area between the curve and the basal body temperature baseline represents the temperature response index.

[0175] 2.4 Statistical methods

[0176] The experimental data were analyzed using SPSS26.0 statistical software, and GraphPadPrism 8.0 software and Origin2021 software were used for drawing graphics. The data results of each experimental group were expressed in the form of mean ± standard deviation (x ± s). In the comparative analysis of the data, the independent sample t-test was used for the comparison between two groups of data; for the comparison between multiple groups of data, one-way analysis of variance (One-Way ANOVA) was used. In addition, repeated measures analysis of variance was used for the comparison between different groups at different time points. P < 0.05 indicates that the difference is statistically significant.

[0177] 2.5 Experimental Results

[0178] 2.5.1 Behavioral changes in rats

[0179] The rats in the blank group had normal body temperature, more activity, good mental state, and normal urination and defecation. After intraperitoneal injection of LPS in the model group and each drug-treated group, as the body temperature increased, the rats all showed symptoms such as shivering and curling up. Most rats had erect hair, prone position, and increased breathing. Some rats even had loose stools and mental depression.

[0180] 2.5.2 Changes in body temperature of rats

[0181] Table 15 Comparison of ΔT values ​​at different time points after intraperitoneal injection of LPS in rats of each group (℃)

[0182] Group 1h 2h 3h 4h 5h 6h Blank group -0.03±0.33 -0.03±0.42 -0.16±0.53 -0.04±0.49 0.35±0.57 0.30±0.55 LPS model group 0.22±0.44 0.05±0.68 0.92±0.77### 1.05±0.69### 1.30±0.49## 1.45±0.50### MGCS low dose group 0.02±0.46 -0.07±0.53 0.28±0.70* 0.40±0.49* 0.53±0.71** 1.12±0.50 MGCS medium dose group -0.05±0.62 -0.22±0.56 0.17±0.67* 0.26±0.58** 0.66±0.71* 1.10±0.65 MGCS high dose group -0.22±0.41 -0.09±0.54 0.25±0.56* 0.36±0.64* 0.45±0.58** 0.69±0.88** ASP control group -0.06±0.51 -0.08±0.54 0.31±0.75* 0.61±0.88 0.73±0.79* 0.73±0.70*

[0183] Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0184] The high, medium and low dose groups of Ma Gui Chai Shi Fang had different degrees of antipyretic effects on the LPS-induced fever model in rats, among which the high dose group had the best antipyretic effect, followed by the medium dose group, and the low dose group had a relatively weak antipyretic effect. Aspirin had a good antipyretic effect, and its antipyretic effect was comparable to that of the high dose group of Ma Gui Chai Shi Fang.

[0185] 2.5.3 HE staining results of rat hypothalamus tissue

[0186] The results are as follows Figure 3 As shown in the results, the high, medium and low dose groups of Magui Chai Shi Fang can alleviate the pathological changes of hypothalamic tissue in rats with LPS-induced fever, improve the narrowing of neuronal intercellular space, the thick staining of cytoplasm, the shrinkage of nuclei and the disordered arrangement, among which the improvement of the high dose group of Magui Chai Shi Fang is better than that of the low and medium dose groups. The state of neuronal cells in the aspirin group was significantly improved and the arrangement was more orderly. This shows that Magui Chai Shi Fang and aspirin have a protective effect on the hypothalamic tissue of febrile rats.

[0187] 2.5.4 Immunohistochemistry and quantitative analysis of rat hypothalamus tissue

[0188] The results are as follows Figure 4 and Figure 5 As shown in the results, the high, medium and low dose groups of Magui Chai Shi Fang can reduce the protein expression of TLR4, COX2, NFκB p65 and TRAF6 in the hypothalamus of febrile rats. The high and medium dose groups can reduce the protein expression of MyD88, alleviate the yellow-brown immune reaction, and reduce the proportion of positive cells. Aspirin can downregulate the expression of COX2, MyD88 and TRAF6 proteins and reduce the proportion of positive nerve cells. This shows that Magui Chai Shi Fang may play an antipyretic effect by regulating the TLR4 / NF-κB / COX2 signaling pathway.

[0189] The levels of inflammatory factors in rat serum and hypothalamus Figure 6 shown.

[0190] Expression of cytokine mRNA in rats Figure 7 shown.

[0191] The mRNA expression of TLR4 / NF-κB / COX2 pathway-related regulatory factors in each group of rats is shown in Figure 8 shown.

[0192] The expression of key target proteins of TLR4 / NF-κB / COX2 pathway in rats in each group is as follows Fig. 9 and Fig.10 shown.

[0193] according to Figure 6-Figure 10It can be seen that compared with the model group, the high-dose group of Magui Chai Shi Fang can significantly reduce the mRNA expression of IL6, IL-1β, TNF-α, CRP, MyD88, NFκB p65, COX2, TRAF6, and TLR4; the medium-dose group can significantly down-regulate the expression of IL-1β, TNF-α, TLR4, MyD88, NFκB p65, and COX2; the low-dose group significantly down-regulated the mRNA expression levels of IL-1β, IFN-α, TNF-α, MyD88, and TLR4; the ASP group can significantly reduce the mRNA expression of IL6, IL-1β, TNF-α, IFN-α, MyD88, COX2, and TLR4. Compared with the model group, the high-dose group of Magui Chai Shi Fang could significantly down-regulate the protein expression of MyD88, COX2, NFκB p65, NFκB pp65, TLR4, and TRAF6, the medium-dose group could significantly down-regulate the protein expression of COX2, NFκB pp65, TLR4, and TRAF6, the low-dose group significantly down-regulated the protein expression of NFκB pp65 and TLR4, and the ASP group could significantly reduce the protein expression of MyD88, NFκB p65, NFκB pp65, and TLR4. This indicates that Magui Chai Shi Fang may play a cooling effect through the TLR4 / NF-κB / COX2 signaling pathway.

[0194] Test Example 3

[0195] Study on the antipyretic mechanism of the Chinese medicine composition of the present invention on rats induced by dry yeast fever

[0196] 3.1 Animal experiments

[0197] A dry yeast-induced rat fever model was used, and different concentrations of the Chinese medicine composition provided in Example 1 of the present invention (granules, the specific dose is the same as in Test Example 1, recorded as Ma Gui Chai Shi Fang) were administered by gavage, and the rat rectal temperature and the expression levels of inflammatory indicators in serum and hypothalamus tissue were measured to investigate the antipyretic effect of Ma Gui Chai Shi Fang on the dry yeast-induced rat fever model; real-time fluorescence quantitative PCR technology and protein immunoblotting (Western Blotting) were used to detect the effect of Ma Gui Chai Shi Fang on the expression of related genes / proteins in the TLR4 / NF-κB / COX2 signaling pathway in dry yeast-induced fever rats.

[0198] 3.2 Construction and grouping of febrile animal models

[0199] According to the experimental operation in 2.2, the rats were randomly divided into blank group, model group, aspirin group (100 mg / kg), and Magui Chai Shi Fang low (7.44 g / kg), medium (14.88 g / kg), and high dose groups (29.76 g / kg), with 12 rats in each group, and each group was recorded as blank group, DY model group, ASP group, MGCS low dose group, MGCS medium dose group, and MGCS high dose group. The rats were gavaged once according to the grouping. Except for the blank group, the rats in other groups were injected with 20% dry yeast suspension at a dose of 10 mL / kg by subcutaneous injection in the back of the neck. An equal volume of normal saline was injected subcutaneously in the back of the blank group rats. After the modeling was completed, the rectal temperature of the rats was measured every 1 hour. Compared with the basal body temperature, it was determined that the modeling was successful. After the modeling was successful (about 5 hours), the drug was administered once again according to the grouping. After the drug administration, the rectal temperature of the rats continued to be monitored for a total of 10 hours, and the temperature change value was calculated.

[0200] 3.3 Observation indicators

[0201] 3.3.1 Behavioral indicators

[0202] Observe the rats for wheezing, shortness of breath, drowsiness, piloerection, and changes in skin color at the extremities.

[0203] 3.3.2 Body temperature

[0204] 1) Observe the changes in body temperature of rats in different drug groups and calculate the maximum temperature rise (ΔTmax): the maximum temperature rise minus the basal body temperature.

[0205] 2) Calculate the 10-hour temperature response index (TRI10).

[0206] 3.4 Statistical methods

[0207] Same as 2.4.

[0208] 3.5 Experimental Results

[0209] 3.5.1 Behavioral changes in rats

[0210] The rats in the blank group had normal body temperature, were active, and were in good spirits. After the dry yeast was injected subcutaneously at the back of the neck, as the body temperature of the rats gradually increased, their activity level decreased significantly, and they showed a clear curled-up posture. At the same time, their feet, auricles, lips, and tails all turned dark red and were accompanied by fever. They even showed symptoms of piloerection, wheezing, and rapid breathing.

[0211] 3.5.2 Changes in body temperature of rats

[0212] Table 16 Comparison of ΔT values ​​at different time points after subcutaneous injection of dry yeast in rats of each group (℃)

[0213] Time (h) Blank group DY Model Group MGCS low dose group MGCS medium dose group MGCS high dose group ASP control group 1 0.21±0.55 <![CDATA[-0.22±0.55 # ]]> -0.07±0.56 -0.06±0.58 -0.06±0.56 -0.08±0.37 2 0.22±0.46 <![CDATA[-0.53±0.50 # ]]> -0.43±0.59 -0.40±0.57 -0.44±0.62 -0.27±0.51 3 0.39±0.40 0.15±0.48 0.63±0.37 0.51±0.37 0.25(0.85) 0.23±0.37 4 0.70±0.60 0.67±0.35 1.08±0.62 1.12±0.60 0.81±0.59 0.30±0.81 5 0.82±0.53 <![CDATA[1.88±0.87 ### ]]> 1.45(0.58) 1.41±0.60 <![CDATA[0.99±0.36 ** ]]> <![CDATA[1.00±0.86 ** ]]> 6 0.47±0.61 <![CDATA[2.39±0.58 ### ]]> <![CDATA[1.46±0.80 ** ]]> <![CDATA[1.62±0.0.76 ** ]]> <![CDATA[1.48±0.54 ** ]]> <![CDATA[1.02±0.78 *** ]]> 7 0.44±0.77 <![CDATA[2.53±0.72 ### ]]> <![CDATA[1.75±0.63 * ]]> <![CDATA[1.88±0.98 * ]]> <![CDATA[1.61±0.71 ** ]]> <![CDATA[0.81±0.93 *** ]]> 8 0.48±0.71 <![CDATA[2.85±0.68 ### ]]> <![CDATA[1.92±0.63 *** ]]> <![CDATA[1.88±0.69 *** ]]> <![CDATA[1.85±0.48 *** ]]> <![CDATA[0.66±0.56 *** ]]> 9 0.49±0.61 <![CDATA[3.01±0.66 ### ]]> <![CDATA[2.16±0.74 ** ]]> <![CDATA[2.05±0.73 ** ]]> <![CDATA[2.07±0.75 ** ]]> <![CDATA[1.03±0.89 *** ]]> 10 0.73±0.50 <![CDATA[2.84±0.37 ### ]]> <![CDATA[2.25(0.85) * ]]> <![CDATA[2.04±0.63 ** ]]> <![CDATA[1.96±0.71 ** ]]> <![CDATA[1.30±0.91 *** ]]>

[0214] Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0215] The high, medium and low dose groups of Ma Gui Chai Shi Fang had different degrees of antipyretic effects on the dry yeast-induced fever model in rats, among which the high dose group had the best antipyretic effect, followed by the medium dose group, and the low dose group had a relatively weak antipyretic effect. Aspirin had a good antipyretic effect, and its antipyretic effect was comparable to that of the high dose group of Ma Gui Chai Shi Fang.

[0216] 3.5.3 HE staining results of rat hypothalamus tissue

[0217] The results are as follows Fig.11 As shown in the results, the high, medium and low dose groups of Magui Chai Shi Fang can alleviate the pathological changes of hypothalamic tissue in rats with dry yeast-induced fever, improve the narrowing of neuronal intercellular space, cytoplasm hyperchromasia, nuclear condensation, disordered arrangement and vacuolar degeneration, among which the improvement of the high dose group of Magui Chai Shi Fang is better than that of the low and medium dose groups. The state of neuronal cells in the aspirin group was significantly improved, and the arrangement was more orderly. This shows that Magui Chai Shi Fang and aspirin have a protective effect on the hypothalamic tissue of febrile rats.

[0218] 3.5.4 Immunohistochemistry and quantitative analysis of rat hypothalamus tissue

[0219] The results are as follows Fig.12 and Fig.13 As shown in the results, the high, medium and low dose groups of Magui Chai Shi Fang can reduce the protein expression of TLR4, MyD88 and COX2 in the hypothalamus of febrile rats; the high and medium dose groups can reduce the protein expression of TRAF6; the high and low dose groups can reduce the protein expression of NFκB p65, reduce the yellow-brown immune reaction, and reduce the proportion of positive cells. Aspirin can downregulate the expression of TLR4, COX2, MyD88, NFκB p65, and TRAF6 proteins and reduce the proportion of positive nerve cells. This shows that Magui Chai Shi Fang may play an antipyretic role by regulating the TLR4 / NF-κB / COX2 signaling pathway.

[0220] The levels of inflammatory factors in rat serum and hypothalamus Fig.14 shown.

[0221] Expression of cytokine mRNA in rats Fig.15 shown.

[0222] The mRNA expression of TLR4 / NF-κB / COX2 pathway-related regulatory factors in each group of rats is shown in Fig.16 shown.

[0223] The expression of key target proteins of TLR4 / NF-κB / COX2 pathway in rats in each group is as follows Fig.17 and Fig.18 shown.

[0224] according to Figure 14-18 It can be seen that compared with the model group, the high-dose group of Magui Chai Shi Fang can significantly reduce the mRNA expression levels of IL6, IL-1β, TNF-α, CRP, MyD88, NFκB p65, COX2, TRAF6, and TLR4; the medium-dose group can significantly down-regulate the expression levels of IL6, CRP, MyD88, NFκB p65, COX2, TLR4, and TRAF6; the low-dose group significantly down-regulated the mRNA expression levels of IL6, CRP, NFκBp65, and TLR4; the ASP group can significantly reduce the mRNA expression levels of IL6 and CRP. Compared with the model group, the high-dose group of Magui Chai Shi Fang could significantly down-regulate the protein expression of MyD88, COX2, NFκBp65, NFκB pp65, TLR4, and TRAF6, the medium-dose group could significantly down-regulate the protein expression of COX2, NFκB p65, TLR4, and TRAF6, the low-dose group could significantly down-regulate the protein expression of MyD88, COX2, TLR4, and TRAF6, and the ASP group could significantly reduce the protein expression of MyD88, COX2, NFκB p65, TLR4, and TRAF6. This indicates that Magui Chai Shi Fang may reduce the phosphorylation level of NF-κBp65 by activating the TLR4 signaling pathway, thereby exerting a cooling effect.

[0225] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating fever, characterized in that: The invention comprises the following raw materials in parts by weight: 7-11 parts of ephedra, 7-11 parts of cassia twig, 10-14 parts of kudzu root, 7-11 parts of apricot kernel, 7-11 parts of white peony root, 2-4 parts of roasted licorice root, 7-11 parts of ginger, 7-11 parts of jujube, 10-14 parts of bupleurum, 7-11 parts of scutellaria, 5-7 parts of ginseng, 7-11 parts of pinellia tuber, 7-11 parts of anemarrhena asphodeloides, and 25-35 parts of gypsum.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 8-10 parts of ephedra, 8-10 parts of cassia twig, 11-13 parts of kudzu root, 8-10 parts of apricot kernel, 8-10 parts of white peony root, 2.5-3.5 parts of roasted licorice root, 8-10 parts of ginger, 8-10 parts of jujube, 11-13 parts of bupleurum, 8-10 parts of scutellaria, 5.5-6.5 parts of ginseng, 8-10 parts of pinellia, 8-10 parts of anemarrhena, and 28-32 parts of gypsum.

3. The Chinese medicine composition according to claim 1, characterized in that The invention comprises the following raw materials in parts by weight: 9 parts of ephedra, 9 parts of cinnamon twig, 12 parts of kudzu root, 9 parts of apricot kernel, 9 parts of white peony root, 3 parts of roasted licorice root, 9 parts of ginger, 9 parts of jujube, 12 parts of bupleurum, 9 parts of scutellaria, 6 parts of ginseng, 9 parts of pinellia, 9 parts of anemarrhena, and 30 parts of gypsum.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating fever.

5. The use according to claim 4, characterized in that: The fever is exogenous fever.

6. The use according to claim 5, characterized in that: The exogenous fever includes fever caused by any one of respiratory infectious diseases, viral encephalitis and lobar pneumonia.

7. The use according to claim 4, characterized in that: The drug for treating fever reduces either or both of the white blood cell count and the neutrophil count, and increases the lymphocyte count.

8. The use according to claim 4, characterized in that: The drug for treating fever exerts a cooling effect via the TLR4 / NF-κB / COX2 signaling pathway.

9. A medicine for treating fever, characterized in that: The medicine contains 0.1-100wt% of the traditional Chinese medicine composition according to any one of claims 1-3.

10. The drug according to claim 9, characterized in that The drug includes pharmaceutically acceptable excipients.

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