CN111729055A

CN111729055A - Preparation method and application of traditional Chinese medicine composition for eliminating dampness and removing toxicity

Info

Publication number: CN111729055A
Application number: CN202010834444.0A
Authority: CN
Inventors: 程学仁; 魏梅; 毛福林; 梁志毅; 曾昭君; 马彩玲; 张志鹏; 鲁云; 邓李红; 徐东婷; 黄梦婷; 姚晓璇; 钟志奎; 陈江平; 王闽予
Original assignee: Guangdong Yifang Pharmaceutical Co Ltd
Current assignee: Guangdong Yifang Pharmaceutical Co Ltd
Priority date: 2020-08-19
Filing date: 2020-08-19
Publication date: 2020-10-02

Abstract

The invention discloses a preparation method of a traditional Chinese medicine composition for eliminating dampness and detoxifying, which comprises the following steps: (1) parching semen Armeniacae amarum, rhizoma Atractylodis and/or fructus Tsaoko; (2) decocting Gypsum Fibrosum in water; (3) adding herba Ephedrae, parched semen Armeniacae amarum, Glycyrrhrizae radix, cortex Magnolia officinalis, bran-parched rhizoma Atractylodis, parched semen Alpiniae, rhizoma Pinelliae Preparata, Poria, radix astragali, semen Lepidii and radix Paeoniae Rubra, and decocting in water; (4) adding herba Agastaches and radix et rhizoma Rhei, decocting in water, and filtering to obtain first decoction and residue; (5) decocting the residue with water, and filtering to obtain second decoction; (6) concentrating the first decoction and the second decoction to obtain fluid extract; (7) processing the fluid extract to obtain a traditional Chinese medicine composition for eliminating dampness and removing toxin; (8) the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxin are determined. Correspondingly, the invention also discloses application of the traditional Chinese medicine composition for eliminating dampness and detoxifying in antiviral drugs. The invention has the effects of eliminating dampness and detoxifying, and dispersing lung qi and clearing heat, and is suitable for light, common and heavy patients with novel coronavirus pneumonia.

Description

Preparation method and application of traditional Chinese medicine composition for eliminating dampness and removing toxicity

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a preparation method and application of a traditional Chinese medicine composition for eliminating dampness and removing toxicity.

Background

Novel coronavirus pneumonia（Corona Virus Disease 2019，COVID-19）This is called "Xinguan pneumonia" for short. The novel coronavirus has the characteristics of strong infectivity, long incubation period, high lethality and the like. Common signs of infection with the novel coronavirus are: fever, cough, shortness of breath and respiratory distressDifficult respiratory symptoms, good prognosis for most patients, critical illness and even death for a few patients. About half of patients have dyspnea after one week, and severe patients rapidly progress to acute respiratory distress syndrome, septic shock, uncorrectable metabolic acidosis and blood coagulation dysfunction, which brings great influence on health and economic development of people and social stability.

According to the clinical characteristics and epidemiological conditions of the patients at present, the experts of the traditional Chinese medicine think that the disease belongs to the category of epidemic diseases of the traditional Chinese medicine, the etiology is the feeling of epidemic crime, and the basic pathogenesis can be summarized as follows: the pathogenic factors invade the exterior, invade the lung channel, the pathogenic factors are strong and healthy and deficient, the pathological nature mainly relates to poison, dampness, cold, heat, dryness, stasis and deficiency, the patient takes the symptoms caused by pathogenic heat resistance lung and lung loss and descent such as fever, cough, asthma and nasal flaring, dyspnea, and the like as the important expression, has extremely strong infectivity and pathogenicity, and is included in the infectious diseases of the second class. The national health and health committee and the national administration of traditional Chinese medicine have issued first to seventh versions of "novel diagnosis and treatment of coronavirus pneumonia" (trial implementation) in succession, and traditional Chinese medicine treatment is recommended from the third version.

The prescription of the dampness-eliminating and toxin-vanquishing traditional Chinese medicine composition is the first traditional Chinese medicine clinical permit for treating the new coronary pneumonia in China according to the national drug administration pharmaceutical clinical trial permit 2020L00009, and becomes the first traditional Chinese medicine approved by China to enter clinical trials for treating the new coronary pneumonia. The applicant utilizes the advanced experience of the production technology in the field of traditional Chinese medicine formula granules, promotes the conversion of scientific and technological achievements, organizes and completes the registration certificate declaration under the technical guidance of Chinese academy of science and technology, and arranges the production and preparation of the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition after obtaining the registration certificate.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a preparation method of the traditional Chinese medicine composition for eliminating dampness and removing toxicity, which is suitable for large-scale production, has stable and controllable production quality, and has the effects of eliminating dampness and removing toxicity, and ventilating and smoothing lung and clearing heat.

The technical problem to be solved by the invention is that the traditional Chinese medicine composition for eliminating dampness and detoxifying is applied to antiviral drugs, and can play an obvious curative effect on light, common and heavy patients with novel coronavirus pneumonia.

In order to solve the technical problems, the invention provides a preparation method of a traditional Chinese medicine composition for eliminating dampness and detoxifying, which comprises the following steps:

(1) parching semen Armeniacae amarum, rhizoma Atractylodis and/or fructus Tsaoko to obtain parched semen Armeniacae amarum, rhizoma Atractylodis parched with bran and/or fructus Tsaoko;

(2) decocting 7.5-150 parts of gypsum in water;

(3) adding 3-60 parts of ephedra, 4.5-90 parts of fried bitter almond, 1.5-30 parts of liquorice, 5-100 parts of mangnolia officinalis, 7.5-150 parts of bran-fried rhizoma atractylodis, 5-100 parts of fried grass nut, 4.5-90 parts of rhizoma pinellinae praeparata, 7.5-150 parts of poria cocos, 5-100 parts of astragalus membranaceus, 5-100 parts of semen lepidii and 5-100 parts of red paeony root, and adding water for decoction;

(4) adding 5-100 parts of patchouli and 2.5-50 parts of rhubarb, adding water, decocting and filtering to obtain a first decoction and dregs;

(5) decocting the residue with water, and filtering to obtain second decoction;

(6) concentrating the first decoction and the second decoction to obtain fluid extract;

(7) mixing the fluid extract and adjuvants, and drying to obtain Chinese medicinal composition with dampness eliminating and toxic materials removing effects;

(8) the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxin are determined.

Preferably, in the step (2), the decoction time of the gypsum is 20-40 minutes, and the water addition amount of the gypsum is 1-6 times of that of the twelve medicines of ephedra herb, fried bitter almond, gypsum, liquorice, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red paeony root.

In the step (3), the water is added for decocting for 40-60 minutes, and the water addition amount is 2-7 times of that of the twelve medicines of ephedra herb, fried bitter almond, gypsum, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red paeony root.

And (4) adding the cablin potchouli herb and the rheum officinale, and decocting the mixture in water for 5-15 minutes, wherein the amount of the added water is 6-10 times that of the cablin potchouli herb and the rheum officinale. Preferably, in the step (4), the cablin potchouli herb and the rhubarb are added, the water is added for decocting for 8-12 minutes, and the water adding amount is 8 times of that of the cablin potchouli herb and the rhubarb.

In the step (5), the decoction dregs are decocted for 40-80 min by adding water, and the water adding amount is 6-10 times of that of the fourteen medicines of ephedra herb, fried bitter apricot seed, gypsum, liquorice, cablin potchouli herb, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, pepperweed seed and red paeony root. Preferably, in the step (5), the decoction dregs are decocted for 50-60 min by adding water, and the water amount is 8 times of that of the fourteen medicines of ephedra herb, fried bitter almond, gypsum, liquorice, pogostemon cablin, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, semen lepidii and red paeony root.

The step (6) comprises the following steps:

respectively concentrating the first decoction and the second decoction under reduced pressure to obtain fluid extract with the relative density of 1.01-1.05, and then combining the fluid extracts and concentrating under reduced pressure to obtain fluid extract with the relative density of 1.06-1.20;

the temperature of the reduced pressure concentration is 45-85 ℃, and the pressure is 0.00-0.095 MPa.

As a further improvement of the invention, the effective components comprise one or more of the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, the content of bound anthraquinone and the content of paeoniflorin.

The invention adopts a high performance liquid chromatography to measure the total content, the total anthraquinone content, the free anthraquinone content and the paeoniflorin content of ephedrine hydrochloride and pseudoephedrine hydrochloride in the dampness eliminating and toxin removing composition, and calculates the content of bound anthraquinone, wherein the content of bound anthraquinone = the total anthraquinone content-the free anthraquinone content.

The total content of the ephedrine hydrochloride and the pseudoephedrine hydrochloride is 0.7-2.7 mg/g;

the content of the paeoniflorin is 3-10 mg/g;

the bound anthraquinone content should not be less than 0.016%.

Correspondingly, the invention also discloses a preparation method of another traditional Chinese medicine composition for eliminating dampness and removing toxicity, which comprises the following steps:

(2) taking 7.5-150 parts of gypsum, 3-60 parts of ephedra, 4.5-90 parts of fried bitter almond, 1.5-30 parts of liquorice, 5-100 parts of mangnolia officinalis, 7.5-150 parts of bran-fried rhizoma atractylodis, 5-100 parts of fried grass nut, 4.5-90 parts of rhizoma pinellinae praeparata, 7.5-150 parts of poria cocos, 5-100 parts of astragalus mongholicus, 5-100 parts of semen lepidii and 5-100 parts of red paeony root, and adding water for decocting;

(3) adding 5-100 parts of patchouli and 2.5-50 parts of rhubarb, adding water, decocting and filtering to obtain a first decoction and dregs;

(4) decocting the residue with water, and filtering to obtain second decoction;

(5) concentrating the first decoction and the second decoction to obtain fluid extract;

(6) mixing the fluid extract and adjuvants, and drying to obtain Chinese medicinal composition with dampness eliminating and toxic materials removing effects;

(7) the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxin are determined.

Preferably, the effective component comprises one or more of total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, content of bound anthraquinone, and content of paeoniflorin.

(2) taking 7.5-150 parts of gypsum, 3-60 parts of ephedra, 4.5-90 parts of fried bitter almond, 1.5-30 parts of liquorice, 5-100 parts of mangnolia officinalis, 7.5-150 parts of bran-fried rhizoma atractylodis, 5-100 parts of fried grass nut, 4.5-90 parts of rhizoma pinellinae praeparata, 7.5-150 parts of poria cocos, 5-100 parts of astragalus mongholicus, 5-100 parts of semen lepidii, 5-100 parts of red paeony root, 5-100 parts of pogostemon cablin and 2.5-50 parts of rheum officinale, adding water for decoction, and filtering to obtain a first decoction and decoction dregs;

(3) decocting the residue with water, and filtering to obtain second decoction;

(4) concentrating the first decoction and the second decoction to obtain fluid extract;

(5) mixing the fluid extract and adjuvants, and drying to obtain Chinese medicinal composition with dampness eliminating and toxic materials removing effects;

(6) the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxin are determined.

Correspondingly, the invention discloses application of the traditional Chinese medicine composition for eliminating dampness and detoxifying prepared by any one of the methods in antiviral drugs. Wherein the antiviral drug is a drug for treating coronavirus. Preferably, the antiviral drug is a new type of coronavirus drug for treating 2019, but is not limited thereto.

The implementation of the invention has the following beneficial effects:

(1) the invention provides a preparation method of a dampness-resolving and toxin-vanquishing traditional Chinese medicine composition, which is prepared from ephedra herb, fried bitter apricot seed, gypsum, liquorice, cablin potchouli herb, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, semen lepidii and red paeony root by a modern production device according to a unified preparation method and a unified production process, and having unified specification, unified dosage and unified quality standard. The preparation method of the dampness-eliminating and toxin-vanquishing traditional Chinese medicine composition is suitable for large-scale production and has the advantages of stable and controllable quality and the like.

(2) The invention effectively detects the total content of ephedrine hydrochloride and pseudoephedrine hydrochloride, the content of combined anthraquinone and the content of paeoniflorin in the dampness-resolving and toxin-vanquishing compositionAnd monitoring to ensure that the traditional Chinese medicine composition is stably controlled within a certain range, thereby ensuring that the traditional Chinese medicine composition pair for eliminating dampness and detoxifyingCOVID-19The key targets of invasion, replication, assembly and shedding transfer correspond to the key action targets of lung injury and inflammatory reaction generated by a host, so that the drug effect is ensured, and the method is suitable for treating light, common and heavy patients with the novel coronavirus pneumonia.

(3) The traditional Chinese medicine composition for eliminating dampness and detoxifying disclosed by the invention has the effects of eliminating dampness and detoxifying, ventilating and purging the lung and clearing heat, has obvious curative effects on treating new coronary lung inflammation with fever, cough, hypodynamia, chest distress, nausea, muscle soreness, dry throat and pharyngalgia, anorexia, sticky and unsmooth mouth and the like, and is suitable for treating novel patients with light, ordinary and heavy coronavirus pneumonia.

Drawings

FIG. 1 is a thin-layer chromatogram of Ephedra sinica Stapf in the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition of the present invention, wherein, 1, 3 μ l of the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004006); 2.3 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3.3 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. ephedrine hydrochloride control 3 μ l;

FIG. 2 is a thin-layer chromatogram of Magnolia officinalis in the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition of the present invention, wherein, 1, 4 μ l of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004006); 2.4 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3.4 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. magnolol control 4 μ l; 5. honokiol control 4 μ l;

FIG. 3 is a thin-layer chromatogram of radix Paeoniae Rubra in the dampness-resolving and toxin-vanquishing Chinese medicinal composition of the present invention, wherein 1. 3. mu.l of dampness-resolving and toxin-vanquishing Chinese medicinal composition (J2004006); 2.3 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3.3 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4.3 μ l of paeoniflorin control;

FIG. 4 is a thin-layer chromatogram of rhubarb in the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition of the invention, wherein 1. 2. mu.l of the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004006); 2.2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3. 2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. 2 mul of rhubarb reference drug;

FIG. 5 is a thin layer chromatogram of radix Glycyrrhizae in the dampness-resolving and toxin-vanquishing Chinese medicinal composition of the present invention, wherein 1. the dampness-resolving and toxin-vanquishing Chinese medicinal composition (J2004006) is 4 μ l; 2.4 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3.4 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. 4 mul of licorice contrast drug;

FIG. 6 is a thin-layer chromatogram of Astragalus membranaceus in the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition of the present invention, wherein 1. 2. mu.l of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004006); 2.2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3. 2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. 2 μ l of astragaloside IV control;

FIG. 7 is a thin-layer chromatogram of semen Lepidii in the dampness-eliminating and toxicity-removing Chinese medicinal composition of the present invention, wherein 1. the dampness-eliminating and toxicity-removing Chinese medicinal composition (J2004006) is 2 μ l; 2.2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004007); 3. 2 mul of dampness-resolving and toxin-vanquishing traditional Chinese medicine composition (J2004008); 4. 2 mul of quercetin-3-O-beta-D-glucose-7-O-beta-D-gentiobioside reference substance;

FIG. 8 is a photograph showing HE staining of lung tissue in a group of Chinese medicinal compositions for eliminating dampness and removing toxicity;

FIG. 9 is a photograph of HE staining of lung tissue of a mouse of the model group.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the accompanying drawings.

The traditional Chinese medicine composition for eliminating dampness and removing toxin comprises: ephedra herb, fried bitter almond, gypsum, liquorice, cablin potchouli herb, officinal magnolia bark, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, Indian buead, rhubarb, astragalus, pepperweed seed and red paeony root.

The Chinese medicinal composition for eliminating dampness and removing toxicity takes ephedra herb, cablin potchouli herb and gypsum as monarch medicaments, and the ephedra herb and the cablin potchouli herb have pungent, bitter and warm odor, relieve exterior syndrome and relieve asthma, eliminate dampness and harmonize the middle warmer; gypsum, gypsum, pungent, sweet and cold in flavor, can clear and purge stagnated heat of lung and stomach and promote the production of body fluid, and the three herbs are combined to achieve the effects of relieving exterior syndrome, dispelling cold, eliminating dampness with aromatics, clearing heat and relieving asthma. The fried bitter almond, the rhizoma pinellinae praeparata, the magnolia officinalis, the rhizoma atractylodis fried with bran, the fried grass nut and the poria cocos are used as ministerial drugs, and the fried bitter almond, the rhizoma pinellinae praeparata and the magnolia officinalis are pungent, bitter and warm, promote qi circulation, descend adverse qi, resolve masses and relieve asthma; stir-frying rhizoma atractylodis and parched tsaoko nut with bran, and the rhizoma atractylodis and the tsaoko nut are pungent, bitter and warm, enter spleen and stomach meridians, dry dampness and invigorate spleen and are knotted by grumpy; poria, with the effects of removing dampness and invigorating spleen; the six herbs are used together to achieve the actions of drying dampness and strengthening spleen, moving qi and unblocking orifices, dredging striae and striae, and helping pathogen go out. Radix astragali, radix Paeoniae Rubra, semen Lepidii, and radix et rhizoma Rhei as adjuvant drugs, radix astragali, radix Et rhizoma Rhei, radix Paeoniae Rubra, radix Et rhizoma Rhei, bitter taste, slight cold, blood cooling, and blood stasis dispelling effects, and can be used for treating diseases such as impairment of vital qi in late stage of epidemic diseases, and blood stasis due to stagnation of qi; ting Li Zi is pungent and cold, and assists the principal drug Gypsum Fibrosum in clearing lung heat, and also has the effect of inducing diuresis to prevent or treat "damp lung (pulmonary edema) lesion"; the rhubarb, radix et rhizoma Rhei, bitter and cold in property, enters the large intestine channel to purge the fu-organs, the lung and the large intestine are exterior and interior, the monarch drug gypsum is used for assisting in clearing lung heat, and the red peony root is used for cooling blood and activating blood, the four drugs are used together as adjuvant drugs to achieve the effects of treating and protecting healthy qi, purging heat and cooling blood, and activating blood and dissolving stasis. The liquorice is used as a guiding drug, the liquorice is sweet and mild, the liquorice is used for harmonizing the effects of the drugs in the recipe, and the radix paeoniae rubra and the liquorice are used for decoction of slow and urgent medicines. The whole formula has the effects of relieving exterior syndrome, eliminating dampness, clearing heat, relieving asthma, tonifying qi and dissipating blood stasis.

Preferably, the traditional Chinese medicine composition for eliminating dampness and removing toxicity comprises: 3-60 parts of ephedra, 4.5-90 parts of fried bitter almond, 7.5-150 parts of gypsum, 1.5-30 parts of liquorice, 5-100 parts of pogostemon cablin, 5-100 parts of mangnolia officinalis, 7.5-150 parts of bran-fried rhizoma atractylodis, 5-100 parts of fried grass nut, 4.5-90 parts of rhizoma pinellinae praeparata, 7.5-150 parts of poria cocos, 2.5-50 parts of rheum officinale, 5-100 parts of astragalus membranaceus, 5-100 parts of semen lepidii and 5-100 parts of red paeony root.

The Chinese ephedra, the patchouli, the gypsum, the fried bitter almond, the rhizoma pinellinae praeparata, the magnolia officinalis, the bran-fried rhizoma atractylodis, the fried bitter almond, the poria cocos, the astragalus mongholicus, the red paeony root, the lepidium seed, the rhubarb and the liquorice are wide in dosage range, the Chinese ephedra can be selected from 3 to 60 parts, the fried bitter almond can be selected from 4.5 to 90 parts, the gypsum can be selected from 7.5 to 150 parts, the liquorice can be selected from 1.5 to 30 parts, the pogostemon cablin can be selected from 5 to 100 parts, the magnolia officinalis can be selected from 5 to 100 parts, the bran-fried rhizoma atractylodis can be selected from 7.5 to 150 parts, the parched bitter almond can be selected from 4.5 to 90 parts, the poria cocos can be selected from 7.5 to 150 parts, the rhubarb can be selected from 2.5 to 50 parts, the astragalus mongholicus can be selected.

More preferably, the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition comprises: 12-36 parts of ephedra, 18-54 parts of fried bitter almond, 30-90 parts of gypsum, 6-18 parts of liquorice, 20-60 parts of patchouli, 20-60 parts of mangnolia officinalis, 30-90 parts of bran-fried rhizoma atractylodis, 20-60 parts of fried grass nut, 18-54 parts of rhizoma pinellinae praeparata, 30-90 parts of poria cocos, 10-30 parts of rheum officinale, 20-60 parts of astragalus membranaceus, 20-60 parts of semen lepidii and 20-60 parts of red paeony root.

Preferably, the traditional Chinese medicine composition for eliminating dampness and removing toxicity comprises the following components:

15-25 parts of ephedra, 26-48 parts of fried bitter almond, 40-80 parts of gypsum, 7-15 parts of liquorice, 25-50 parts of patchouli, 25-50 parts of mangnolia officinalis, 25-70 parts of bran-fried rhizoma atractylodis, 25-50 parts of fried grass nut, 25-40 parts of rhizoma pinellinae praeparata, 40-80 parts of poria cocos, 15-25 parts of rheum officinale, 25-50 parts of astragalus membranaceus, 25-50 parts of semen lepidii and 25-50 parts of red paeony root.

The dampness-resolving and toxin-vanquishing formula consists of fourteen medicines of ephedra, cablin potchouli herb, gypsum, fried bitter apricot seed, rhizoma pinellinae praeparata, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, poria cocos, astragalus, red paeony root, semen lepidii, rhubarb and liquorice, and is generally prepared into a traditional decoction by traditional Chinese medicine decoction pieces for taking.

Therefore, the invention provides a preparation method of various dampness-resolving and toxin-vanquishing traditional Chinese medicine compositions, and the dampness-resolving and toxin-vanquishing traditional Chinese medicine compositions with unified specification, unified dosage and unified quality standard are prepared from the fourteen medicines by using modern production equipment strictly according to a unified preparation method and a unified production process.

The first preferred embodiment of the preparation method of the traditional Chinese medicine composition for eliminating dampness and removing toxicity comprises the following steps:

(2) decocting 7.5-150 parts of gypsum in water;

(5) decocting the residue with water, and filtering to obtain second decoction;

In this embodiment, gypsum is a monarch drug, belongs to a mineral drug, and the active ingredients are not easy to be decocted, i.e. should be decocted for about 30 minutes, and then other drugs are added to be decocted; herba Agastaches is the monarch drug, relieve exterior syndrome and relieve asthma, resolve dampness and regulate the middle warmer, the effective component should be added after being decocted because of easy volatilization, when decocting, the decoction is put into boiling for several minutes; rhubarb, which is an adjuvant drug and mainly has the functions of clearing lung heat, activating blood and cooling blood, is realized by the combined anthraquinone (aloe-emodin, rhein, emodin, chrysophanol and physcion) introduced into rhubarb, but the combined anthraquinone is easily decomposed into free anthraquinone when being heated, so that the drug effect is weakened. Therefore, Da Huang should be decocted later.

The dampness eliminating and toxin removing composition prepared by the method can control the content of ephedrine hydrochloride and pseudoephedrine hydrochloride to be 0.7-2.7 mg/g; the content of paeoniflorin is controlled to be 3-14 mg/g; the content of the combined anthraquinone is controlled to be not less than 0.016 percent, thereby ensuring the curative effect and being suitable for patients with light, common and heavy type coronavirus pneumonia.

The dampness-resolving and toxin-vanquishing traditional Chinese medicine composition prepared by the method has the advantages of convenience in carrying, direct taking, stable and controllable quality and the like, is more suitable for the modern clinical urgent need of medicine, can be directly applied to the clinical treatment of traditional Chinese medicine, is further popularized and popularized to the clinical application of the traditional Chinese medicine, and solves the problems that the dampness-resolving and toxin-vanquishing decoction is complex in decocting process, long in decocting time, inconvenient to store, carry and transport and extremely inconvenient to clinically and urgently need a large amount of medicine and the like.

However, in the above preparation method, in addition to the order of adding the fourteen herbs in the decoction process, the amount of water added, the decoction time, the number of times of decoction, the concentration method and the relative density of the clear paste are also key factors, which affect the curative effect of the dampness-resolving and toxicity-removing traditional Chinese medicine composition, and affect the content of paeoniflorin, the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, and the content of anthraquinone. The invention is further illustrated below with reference to the technical details of the individual steps:

in the step (1), the bitter almond, the rhizoma atractylodis and/or the tsaoko nut are fried in advance to obtain fried bitter almond, bran-fried rhizoma atractylodis and/or sauted tsaoko nut. Wherein, the stir-fried bitter almond contains higher amygdalin content and has obvious effects of relieving cough and asthma, the stir-fried rhizoma atractylodis with bran can improve the effect of the rhizoma atractylodis in treating phlegm-dampness encumbering the spleen, can effectively recover the content of AQP2 and AQP3 in the alimentary tract and the content of serum ADH, and the stir-fried grass nut can alleviate dryness and avoid causing gastrointestinal discomfort.

Preferably, the fried bitter almond is prepared by the following method: scalding semen Armeniacae amarum, placing in a hot pan, and parching with slow fire to surface yellow or brown yellow with slight focus and fragrance.

The main component of the bitter apricot kernel is amygdalin which plays a pharmacological role of relieving cough and asthma by decomposing into hydrocyanic acid. Pharmacodynamic researches show that 4 bitter almond test solutions (fried bitter almond, later bitter almond, blanched bitter almond and raw bitter almond) have obvious effects of relieving cough and asthma. The invention selects the fried bitter almond with proper content of amygdalin, and can play a role in obviously relieving cough and asthma when treating 2019 novel coronavirus.

Preferably, the rhizoma atractylodis stir-fried with bran is prepared by the following method: heating the hot pot until bran is scattered and the bran is immediately smoked, putting the rhizoma atractylodis slices into the hot pot, rapidly turning, frying until the surface is dark yellow, taking out the hot pot, screening off the bran, and cooling. 10-15 kg of bran is used for every 100kg of rhizoma atractylodis tablets.

Raw and bran-fried rhizoma atractylodis can reduce the water content of large intestine of a model rat, and increase the serum GAS content and AMS content, however, the bran-fried rhizoma atractylodis is added in the invention, so that the content of AQP2 and AQP3 in a digestive tract and the content of serum ADH can be restored, and the effect of the rhizoma atractylodis on treating phlegm-dampness encumbering the spleen is improved.

Preferably, the parched tsaoko nuts are prepared by the following method: taking fructus Tsaoko, removing impurities, placing in a hot pan, parching with slow fire until the surface turns brown and slightly swells, taking out, removing shell, and taking out kernel; taking the tsaoko nutlet, putting into a hot pot, frying with slow fire until the surface bulges and the fragrance escapes, taking out, and cooling.

The warm and dry property of the tsaoko amomum fruit is obvious, and the stir-fried tsaoko amomum fruit is used, so that the dryness can be alleviated, and the gastrointestinal discomfort can be avoided.

In the step (2), the gypsum is decocted firstly, and the decocting time of the gypsum is 20-40 minutes, so that the gypsum meets the characteristics of the gypsum and is beneficial to decocting the effective components. Preferably, the decoction time of the gypsum is about 30 minutes.

The water adding amount in the step (2) is 1-6 times of the water adding amount of the twelve medicines of ephedra, fried bitter apricot seed, gypsum, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus membranaceus, semen lepidii and red paeony root, and the water adding amount is set by combining the production conditions of large-scale production equipment, so that the gypsum and the following effective ingredients of the medicines can be decocted, and meanwhile, the method is suitable for mass production.

In the step (3), the water is added for decocting for 40-60 minutes. After the gypsum is decocted, the ephedra, the fried bitter almond, the liquorice, the mangnolia officinalis, the bran-fried rhizoma atractylodis, the fried grass nut, the rhizoma pinellinae praeparata, the poria cocos, the astragalus membranaceus, the pepperweed seed and the red paeony root are added and decocted for 40-60 minutes, so that the effective components of the ephedra, the fried bitter almond, the liquorice, the mangnolia officinalis, the bran-fried rhizoma atractylodis, the fried grass nut, the rhizoma pinellinae praeparata, the poria cocos, the astragalus membranaceus, the pepper. Preferably, the time for decocting the water in the step (3) is 50 minutes.

The water adding amount of the step (3) is 2-7 times of the water amount of the twelve medicines of ephedra, fried bitter apricot seed, gypsum, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red paeony root. The water adding amount is set by combining the production conditions of large-scale production equipment, so that the effective components of ephedra, fried bitter apricot kernels, gypsum, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nuts, rhizoma pinellinae praeparata, poria cocos, astragalus membranaceus, semen lepidii and red paeony root can be decocted, and the method is suitable for mass production.

And (4) adding the cablin potchouli herb and the rheum officinale, and decocting the mixture in water for 5-15 minutes. And (3) adding the patchouli and the rheum officinale in the step (4) to avoid volatilization or weakening of effective components caused by decoction, wherein the decoction time of the patchouli and the rheum officinale is only 5-15 minutes, and the volatilization or weakening of the effective components can be avoided.

The water adding amount in the step (4) is 6-10 times of that of the patchouli and the rheum officinale. The water adding amount is set by combining the production conditions of large-scale production equipment, so that the continuous decoction of the effective components of the ephedra herb, the fried bitter apricot kernel, the gypsum, the liquorice, the mangnolia officinalis, the bran-fried rhizoma atractylodis, the fried grass nut, the rhizoma pinellinae praeparata, the poria cocos, the astragalus mongholicus, the semen lepidii and the red paeony root and the decoction of the effective components of the patchouli and the rhubarb are facilitated, and the method is simultaneously suitable for large-scale production.

Preferably, in the step (4), the cablin potchouli herb and the rhubarb are added, the water is added for decocting for 8-12 minutes, and the water adding amount is 8 times of that of the cablin potchouli herb and the rhubarb.

In the step (5), the decoction dregs are decocted for 40-80 min by adding water, and the water adding amount is 6-10 times of that of the fourteen medicines of ephedra herb, fried bitter apricot seed, gypsum, liquorice, cablin potchouli herb, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, pepperweed seed and red paeony root. The invention carries out decoction again on the dregs of a decoction, is beneficial to fully decocting the effective components and improves the efficacy of the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition.

Preferably, in the step (5), the medicine residues are decocted for 50-60 min by adding water, and the water amount is 8 times of that of the fourteen medicines of ephedra herb, fried bitter almond, gypsum, liquorice, pogostemon cablin, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, semen lepidii and red paeony root.

The step (6) comprises the following steps:

respectively carrying out vacuum concentration on the first decoction and the second decoction to obtain clear paste with the relative density of 1.01-1.05, and then combining the clear pastes and carrying out vacuum concentration to obtain clear paste with the relative density of 1.06-1.20. The fluid extract has good fluidity and appropriate amount, and is suitable for mass production.

Preferably, the temperature of the reduced pressure concentration is 45-85 ℃, and the pressure is 0.00-0.095 MPa. The condition of decompression concentration can ensure the stability of the components to the maximum extent when the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition is produced in a large scale.

And (7) uniformly mixing the clear paste and auxiliary materials, and drying to obtain the traditional Chinese medicine composition for eliminating dampness and detoxifying. Preferably, the drying is at least one of spray drying, belt drying, or freeze drying, but is not limited thereto. The person skilled in the art can select a suitable drying means depending on the actual production conditions.

The dampness-resolving toxin-vanquishing traditional Chinese medicine composition is processed correspondingly to obtain a dampness-resolving toxin-vanquishing traditional Chinese medicine preparation which can be granules, decoctions, powder, capsules, oral liquid, tablets, pills and the like, but is not limited to the preparation. The processing method depends on different dosage forms, and the processing method is set according to the prior art.

In the step (8), the effective components of the traditional Chinese medicine composition for eliminating dampness and detoxifying are measured.

The effective components include one or more of total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, content of bound anthraquinone, and content of paeoniflorin.

The invention adopts a high performance liquid chromatography to measure the total content, the total anthraquinone content, the free anthraquinone content and the paeoniflorin content of ephedrine hydrochloride and pseudoephedrine hydrochloride in the dampness eliminating and toxin removing composition, and calculates the content of bound anthraquinone, wherein the content of bound anthraquinone = the total anthraquinone content-the free anthraquinone content. Wherein the total content of the ephedrine hydrochloride and the pseudoephedrine hydrochloride is 0.7-2.7 mg/g; the content of the paeoniflorin is 3-14 mg/g; the bound anthraquinone content should not be less than 0.016%.

In the research process, the inventor adopts the molecular docking technology to mix various traditional Chinese medicines and the Chinese medicines in the formula of the dampness-resolving and toxin-vanquishing compositionCOVID-19Key targets for invasion, replication, assembly, desquamation and metastasis, as well as key targets for the host's development of pulmonary injury and inflammatory response. The results show that: ephedra is responsive to TMPRSS2, TACE, AAK1 (viral entry, endocytosis regulation), which are targets for inhibiting viral entry and shedding, VEGFR2 (vascular permeability) and ALK5 (vascular permeability, pulmonary fibrosis), which are critical targets for tissue damage following viral entry into the host. Rheum officinale for inhibiting virus invasion and sheddingThe target TMPRSS2, the critical targets for tissue damage following viral entry into the host, AMPK, VEGFR2 and ALK5, respond. Red peony responds to the targets Mpro and ACE 2.

The ephedra in the composition for eliminating dampness and detoxifying mainly plays roles in ventilating lung qi, reducing phlegm and relieving cough, belongs to monarch drugs in the principle of a traditional Chinese medicine formula and plays an important role in the formula. Meanwhile, ephedrine introduced by the ephedra is volatile and is easy to lose in the process of large-scale production. Therefore, the invention controls the contents of ephedrine hydrochloride and pseudoephedrine hydrochloride, and the contents of the ephedrine hydrochloride and the pseudoephedrine hydrochloride are 0.7-2.7 mg/g, thereby ensuring the curative effect of the dampness-resolving and toxin-vanquishing composition.

Rhubarb in the composition for eliminating dampness and detoxifying has the main functions of clearing away lung heat, promoting blood circulation and cooling blood, and is mainly realized by the combined anthraquinone (aloe-emodin, rhein, emodin, chrysophanol and physcion) introduced into rhubarb. However, bound anthraquinone readily decomposes to free anthraquinone upon heating, resulting in a decrease in efficacy. Therefore, the content of the conjugated anthraquinone needs to be controlled, and the content of the conjugated anthraquinone is not less than 0.016 percent, so that the curative effect of the dampness eliminating and toxin removing composition is ensured.

Note that the bound anthraquinone content = total anthraquinone content — free anthraquinone content. In specific implementation, the content of the total anthraquinone and the content of the free anthraquinone in the dampness eliminating and toxin removing composition can be measured through high performance liquid chromatography, and then the content of the bound anthraquinone can be calculated.

In addition, in the dampness eliminating and toxin removing composition, the content of paeoniflorin is 3-14 mg/g, and the curative effect of the dampness eliminating and toxin removing composition is further ensured by controlling the content of paeoniflorin.

The second preferred embodiment of the preparation method of the traditional Chinese medicine composition for eliminating dampness and removing toxicity comprises the following steps:

(4) decocting the residue with water, and filtering to obtain second decoction;

Unlike the first embodiment, in this embodiment, the gypsum is directly decocted with the ephedra herb, the fried bitter apricot seed, the liquorice, the officinal magnolia bark, the bran-fried rhizoma atractylodis, the fried grass nut, the rhizoma pinellinae praeparata, the tuckahoe, the astragalus, the pepperweed seed and the red paeony root.

In the embodiment, the water adding amount in the step (2) is 5-15 times of water of gypsum, ephedra herb, fried bitter apricot seed, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red paeony root, and the decocting time is 40-120 minutes.

Herba Agastaches is the monarch drug, relieve exterior syndrome and relieve asthma, resolve dampness and regulate the middle warmer, the effective component should be added after being decocted because of easy volatilization, when decocting, the decoction is put into boiling for several minutes; rhubarb, which is an adjuvant drug and mainly has the functions of clearing lung heat, activating blood and cooling blood, is realized by the combined anthraquinone (aloe-emodin, rhein, emodin, chrysophanol and physcion) introduced into rhubarb, but the combined anthraquinone is easily decomposed into free anthraquinone when being heated, so that the drug effect is weakened. Therefore, Da Huang should be decocted later.

In the step (7), the invention needs to determine the effective components of the traditional Chinese medicine composition for eliminating dampness and detoxifying. Preferably, the effective component comprises one or more of total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, content of bound anthraquinone, and content of paeoniflorin.

The gypsum, the ephedra herb and the red paeony root of the embodiment are added together with other medicines, and the rhubarb and the cablin potchouli herb are added finally, although the gypsum is not decocted firstly, the gypsum is decocted with the rest eleven medicines for 40-120 minutes, so that the effective components can be basically decocted out, and the effects of relieving exterior syndrome, dispelling cold, aromatizing, eliminating dampness, clearing heat and relieving asthma can be basically achieved. In the embodiment, the rhubarb is added finally, so that the contents of the ephedrine hydrochloride and the pseudoephedrine hydrochloride can be controlled to be 0.7-2.7 mg/g; the content of paeoniflorin is controlled to be 3-10 mg/g; the content of the combined anthraquinone is controlled to be not less than 0.016 percent, thereby ensuring the curative effect and being suitable for patients with light, common and heavy type coronavirus pneumonia.

It should be noted that the amount of water added, the decocting time and other technical details of the other steps may be set with reference to the first embodiment.

The third preferred embodiment of the preparation method of the traditional Chinese medicine composition for eliminating dampness and removing toxicity comprises the following steps:

(3) decocting the residue with water, and filtering to obtain second decoction;

Different from the first and second embodiments, the fourteen medicines are decocted together. The water adding amount in the step (2) is 5-15 times of that of ephedra, fried bitter apricot seed, gypsum, liquorice, cablin potchouli herb, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus membranaceus, semen lepidii and red paeony root, and the decocting time is 20-120 minutes.

The traditional Chinese medicine composition for dissipating dampness and detoxifying basically has the effects of dissipating dampness and detoxifying, ventilating and smoothing the lung and clearing heat, has preliminary curative effects on treating new coronary lung inflammation with fever, cough, hypodynamia, chest distress, nausea, muscle soreness, dry throat, pharyngalgia, anorexia, sticky and uncomfortable mouth and the like, and is suitable for treating light, common and heavy patients with novel coronavirus pneumonia.

In the step (6), the invention needs to determine the effective components of the traditional Chinese medicine composition for eliminating dampness and detoxifying. Preferably, the effective component comprises one or more of total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, content of bound anthraquinone, and content of paeoniflorin.

The fourteen medicines are added and decocted together, and the contents of ephedrine hydrochloride and pseudoephedrine hydrochloride can be controlled to be 0.7-2.7 mg/g; the content of paeoniflorin is controlled to be 3-10 mg/g, and parameters in the process are further adjusted by measuring the total content of ephedrine hydrochloride and pseudoephedrine hydrochloride and the content of paeoniflorin.

The technical details of the other steps may be set with reference to the first embodiment.

The traditional Chinese medicine composition for eliminating dampness and detoxifying can be applied to treatment of various virus diseases, such as 2019 novel coronavirus or other diseases. As long as the pathogenesis of the virus diseases is damp toxin stagnation, the traditional Chinese medicine composition for eliminating dampness and removing toxin can be reasonably used as a main treatment means or an auxiliary treatment means.

The traditional Chinese medicine composition for eliminating dampness and detoxifying is particularly suitable for treating 2019 patients with the novel coronavirus. The early-stage clinical observation shows that the traditional Chinese medicine composition can improve the clinical symptoms of severe novel coronavirus infection pneumonia, can obviously relieve main symptoms of cough, hypodynamia, xerostomia or vomit and the like for severe patients, shortens the curing time after the traditional Chinese medicine and western medicine are combined for treatment, obviously improves the respiratory function of the patients, and shortens the time for separating from oxygen inhalation. For light and common patients, the traditional Chinese medicine composition can obviously relieve fever symptoms and also can improve anorexia and chest distress symptoms. The medicine has obvious improvement on the clinical symptoms of cough, hypodynamia, dry mouth or vomit and the like of the light, heavy and common novel coronavirus infection pneumonia, and supplements the heavy, light and common novel coronavirus infection pneumonia treatment medicine which is urgently needed in the current epidemic situation.

The present invention is further illustrated by the following specific examples, in which examples 1 to 8 are the dampness-eliminating and toxin-vanquishing composition (granules) prepared by the preparation method of the first embodiment, example 9 is the dampness-eliminating and toxin-vanquishing composition (granules) prepared by the preparation method of the second embodiment, and example 10 is the dampness-eliminating and toxin-vanquishing composition (granules) prepared by the preparation method of the third embodiment.

Example 1

The preparation steps of the dampness-eliminating and toxin-removing granules of the embodiment are as follows:

(1) the preparation raw materials comprise: 24 parts of ephedra decoction pieces, 40 parts of pogostemon cablin decoction pieces, 60 parts of gypsum decoction pieces, 36 parts of fried bitter almond decoction pieces, 36 parts of rhizoma pinellinae praeparata decoction pieces, 40 parts of mangnolia officinalis decoction pieces, 60 parts of bran-fried rhizoma atractylodis decoction pieces, 40 parts of fried grass nut decoction pieces, 60 parts of poria cocos decoction pieces, 40 parts of astragalus mongholicus decoction pieces, 40 parts of red paeony root decoction pieces, 40 parts of semen lepidii decoction pieces, 20 parts of rheum officinale decoction pieces, 12 parts of liquorice decoction pieces, 50 parts of dextrin and 0.6 part of.

(2) Preparing dampness-resolving toxin-vanquishing granules: taking the total crude drug quantity of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 548kg, adding 2440L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rheum officinale, adding 1464L of water, decocting for 50 minutes, adding the patchouli and the rheum officinale, adding 480L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 4384L of water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 2

(2) Preparing dampness-resolving toxin-vanquishing granules: taking the total crude drug quantity of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 548kg, adding 2440L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rheum officinale, adding 1464L of water, decocting for 50 minutes, adding the patchouli and the rheum officinale, adding 480L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 4384L of water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, boiling, granulating, drying, and packaging to obtain dampness eliminating and toxic materials removing granule.

Example 3

(2) Preparing dampness-resolving toxin-vanquishing granules: taking the total crude drug quantity of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 548kg, adding 2440L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rheum officinale, adding 1464L of water, decocting for 50 minutes, adding the patchouli and the rheum officinale, adding 480L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 4384L of water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, drying, granulating, drying, and packaging to obtain dampness eliminating and toxic materials removing granule.

Example 4

(2) Preparing dampness-resolving toxin-vanquishing granules: taking the total crude drug amount of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 548kg, adding 488L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rheum officinale, adding 3416L of water, decocting for 50 minutes, adding the patchouli and the rheum officinale, adding 480L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 4384L of water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 5

(1) the preparation raw materials comprise: 12 parts of ephedra decoction pieces, 20 parts of pogostemon cablin decoction pieces, 30 parts of gypsum decoction pieces, 18 parts of fried bitter almond decoction pieces, 18 parts of rhizoma pinellinae praeparata decoction pieces, 20 parts of mangnolia officinalis decoction pieces, 30 parts of bran-fried rhizoma atractylodis decoction pieces, 20 parts of fried grass nut decoction pieces, 30 parts of poria cocos decoction pieces, 20 parts of astragalus mongholicus decoction pieces, 20 parts of red paeony root decoction pieces, 20 parts of semen lepidii decoction pieces, 10 parts of rhubarb decoction pieces, 6 parts of liquorice decoction pieces, 25 parts of dextrin and 0.3 part of stevio.

(2) Preparing dampness-resolving toxin-vanquishing granules: taking total crude drug quantity of dampness eliminating and toxin removing formula decoction pieces to be 274kg, adding 1464L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rhubarb, adding 488L of water, decocting for 50 minutes, adding the patchouli and the rhubarb, adding 240L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; decocting the residue with 2192L water for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 6

(1) the preparation raw materials comprise: 36 parts of ephedra decoction pieces, 60 parts of pogostemon cablin decoction pieces, 90 parts of gypsum decoction pieces, 54 parts of fried bitter almond decoction pieces, 54 parts of rhizoma pinellinae praeparata decoction pieces, 60 parts of mangnolia officinalis decoction pieces, 90 parts of bran-fried rhizoma atractylodis decoction pieces, 60 parts of fried grass nut decoction pieces, 90 parts of poria cocos decoction pieces, 60 parts of astragalus mongholicus decoction pieces, 60 parts of red paeony root decoction pieces, 60 parts of semen lepidii decoction pieces, 30 parts of rheum officinale decoction pieces, 18 parts of liquorice decoction pieces, 99 parts of dextrin and 1 part of.

(2) Preparing dampness-resolving toxin-vanquishing granules: taking 822kg of total crude drug of dampness eliminating and toxin removing formula decoction pieces, adding 2196L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except for the patchouli and the rheum officinale, adding 3660L of water, decocting for 50 minutes, adding the patchouli and the rheum officinale, adding 720L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 6576L water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 7

(1) the preparation raw materials comprise: 3 parts of ephedra decoction pieces, 5 parts of pogostemon cablin decoction pieces, 7.5 parts of gypsum decoction pieces, 4.5 parts of fried bitter almond decoction pieces, 4.5 parts of rhizoma pinellinae praeparata decoction pieces, 5.0 parts of mangnolia officinalis decoction pieces, 7.5 parts of bran-fried rhizoma atractylodis decoction pieces, 5.0 parts of fried grass nut decoction pieces, 7.5 parts of poria cocos decoction pieces, 5.0 parts of astragalus membranaceus decoction pieces, 5.0 parts of red paeony root decoction pieces, 5.0 parts of semen lepidii decoction pieces, 2.5 parts of rhubarb decoction pieces, 1.5 parts of liquorice decoction pieces, 5.5 parts of dextrin and 0.05 part of stevioside.

(2) Preparing dampness-resolving toxin-vanquishing granules: taking the total crude drug amount of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 68.5kg, adding 305L of water into gypsum, decocting for 30 minutes, adding the rest eleven materials except the cablin potchouli herb and the rhubarb, adding 183L of water, decocting for 50 minutes, adding the cablin potchouli herb and the rhubarb, adding 60L of water, decocting for 10 minutes again, and filtering to obtain a first decoction and dregs; adding 548L of water into the dregs of the decoction, decocting for 1 hour, and filtering to obtain a second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 8

(1) the preparation raw materials comprise: 60 parts of ephedra decoction pieces, 100 parts of pogostemon cablin decoction pieces, 150 parts of gypsum decoction pieces, 90 parts of fried bitter almond decoction pieces, 90 parts of rhizoma pinellinae praeparata decoction pieces, 100 parts of mangnolia officinalis decoction pieces, 150 parts of bran-fried rhizoma atractylodis decoction pieces, 100 parts of fried grass nut decoction pieces, 150 parts of poria cocos decoction pieces, 100 parts of astragalus mongholicus decoction pieces, 100 parts of red paeony root decoction pieces, 100 parts of semen lepidii decoction pieces, 50 parts of rheum officinale decoction pieces, 30 parts of liquorice decoction pieces, 179 parts of dextrin and 2 parts of.

(2) Preparing dampness-resolving toxin-vanquishing granules: taking total crude drug quantity of the dampness-resolving and toxin-vanquishing formula decoction pieces to be 1370kg, adding 6100L of water into the gypsum for decoction for 30 minutes, adding the rest eleven materials except the cablin potchouli herb and the rhubarb, adding 3660L of water for decoction for 50 minutes, adding the cablin potchouli herb and the rhubarb, adding 1200L of water for decoction for 10 minutes, and filtering to obtain a first decoction and dregs; adding 10960L water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 9

(2) Preparing dampness-resolving toxin-vanquishing granules: taking 822kg of total crude drug of dampness eliminating and toxin removing prescription decoction pieces, taking fried bitter almond, gypsum, liquorice, mangnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus membranaceus, semen lepidii and radix paeoniae rubra, adding 5856L of water, decocting for 50 minutes, adding patchouli and rheum officinale, adding 720L of water, decocting for 10 minutes, and filtering to obtain a first decoction and dregs; adding 6576L water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Example 10

(2) Preparing dampness-resolving toxin-vanquishing granules: taking 822kg of total crude drug of dampness eliminating and toxin removing prescription decoction pieces, taking ephedra, fried bitter almond, gypsum, liquorice, pogostemon cablin, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus mongholicus, semen lepidii and red paeony root, adding 6576L of water, decocting for 1 hour, and filtering to obtain a first decoction and dregs; adding 6576L water into the residue, decocting for 1 hr, and filtering to obtain second decoction; respectively carrying out reduced pressure concentration on the first decoction and the second decoction at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.01-1.05, combining the first decoction and the second decoction, and carrying out reduced pressure concentration at the temperature of 45-85 ℃ until the relative density of the first decoction and the second decoction is 1.06-1.20; adding dextrin and steviosin, mixing, spray drying, adding dextrin, mixing, dry granulating, and packaging to obtain dampness eliminating and toxic substance removing granule.

Now, the content of the components in examples 1 to 10 was measured as follows:

method for measuring content of index component

Paeoniflorin: the measurement is carried out by high performance liquid chromatography (0512 in the four-department general regulation of the 2015 edition in China pharmacopoeia).

Chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; methanol-0.05 mol/L potassium dihydrogen phosphate solution (35: 65) is used as a mobile phase; the detection wavelength is 230 nm; the flow rate was 1ml per minute; the column temperature was 30 ℃. The number of theoretical plates is not less than 3000 calculated according to paeoniflorin peak.

Preparation of control solutions: taking appropriate amount of penoniflorin reference substance, precisely weighing, and adding methanol to obtain reference substance solution containing 0.13mg per 1 ml.

Preparation of a test solution: taking a proper amount of the product, grinding, precisely weighing about 1.0g, placing in a conical flask with a plug, precisely adding 25ml of methanol, weighing, heating and refluxing for 30 minutes, cooling, weighing again, supplementing the lost weight with methanol, shaking uniformly, filtering, and taking the subsequent filtrate.

The determination method comprises the following steps: precisely sucking 10 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.

Ephedrine hydrochloride and pseudoephedrine hydrochloride: the measurement is carried out according to high performance liquid chromatography (China pharmacopoeia 2015 edition of the general rules 0512 in four parts).

Chromatographic conditions and system applicability test: polar ether is connected with phenyl bonded silica gel as a filling agent; methanol-0.092% phosphoric acid solution (containing 0.04% triethylamine and 0.02% diethylamine) (1.5: 98.5) as mobile phase; the detection wavelength is 210 nm; the column temperature was 35 ℃; the flow rate was 0.8ml per minute. The number of theoretical plates is not less than 3000 calculated according to ephedrine hydrochloride peak.

Preparation of control solutions: taking appropriate amount of ephedrine hydrochloride reference substance and pseudoephedrine hydrochloride reference substance, precisely weighing, and adding methanol to obtain mixed solution containing 10 μ g of each 1 ml.

Preparation of a test solution: taking a proper amount of the product, grinding, taking about 0.5g, precisely weighing, placing in a conical flask with a plug, precisely adding 50ml of 0.1mol/L hydrochloric acid solution, weighing, carrying out ultrasonic treatment (power 250W and frequency 40 kHz) for 30 minutes, cooling, weighing again, supplementing the lost weight with 0.1mol/L hydrochloric acid solution, shaking uniformly, centrifuging (rotation speed is 4000 revolutions per minute) for 5 minutes, taking supernatant, filtering, precisely weighing 25ml of subsequent filtrate, adding on a solid phase extraction column (taking a mixed type cation exchange reverse phase adsorbent as a filler, 150mg and 6ml, pre-washing with 6ml of methanol and water respectively), eluting with 6ml of each of 0.lmol/L hydrochloric acid solution and methanol respectively, discarding the eluent, eluting with 10ml of newly prepared acetonitrile-concentrated ammonia test solution (95: 5), collecting the eluent, placing in a 10ml measuring flask, adding the mixed solution to dilute to scale, shaking up to obtain the final product.

(II) index measurement results

The content of paeoniflorin, ephedrine hydrochloride and pseudoephedrine hydrochloride of the samples of examples 1-10 were measured, and the measurement results are shown in Table 1.

TABLE 1 content of the index components in the preparation examples of dampness-eliminating and toxin-removing granules

Note: 5g of dampness-resolving and toxin-vanquishing granules are packaged in each bag.

As can be seen from the index component contents of examples 1 to 10 in Table 1, the contents of paeoniflorin, ephedrine hydrochloride and pseudoephedrine hydrochloride in the dampness-resolving and toxicity-removing granules prepared in different process parameter ranges, different drying modes, different granulation modes and different batches in the examples of the invention can be stably controlled within a certain range.

As can be seen from comparison of the results in embodiments 1 to 10, the effect of the present invention can also be achieved by adjusting each parameter, each technical feature can be arbitrarily combined, and for brevity of description, all possible combinations of each technical feature in the above embodiments are not described, however, as long as there is no contradiction between the combinations of the technical features, the scope of protection of the present invention should be considered.

Further, the dampness-resolving and toxin-vanquishing particles prepared according to the first embodiment of the present invention are subjected to detection and efficacy tests, specifically as follows:

firstly, selecting dampness-eliminating and toxin-removing granules of three batches (with the batch numbers of J2004006, J2004007 and J2004008) of the invention for relevant detection, and specifically comprising the following steps:

the test results of the product batch number J2004006 are shown in the following table 2:

the test result of product batch J2004007 is shown in the following Table 3:

(III) the test results of product batch J2004008 are shown in Table 4 below:

it should be noted that the above-mentioned dampness-resolving and toxin-vanquishing granules have the following packaging specifications: each bag is 5 g.

Secondly, the prescription of the dampness-resolving and toxin-vanquishing particle of the invention is subjected to pharmacodynamic experiments, namely the observation of the SARS-CoV-2 infection resistance, and the results are as follows:

materials and methods

1. Test drug

Subject name: dampness-resolving toxin-vanquishing granule

The provider of the test substance: chinese academy of traditional Chinese medicine

Test article lot number: 20200202

Preparing a test substance: dissolving 2.25g of the medicinal powder in water or mixing, diluting to 10ml, and shaking to obtain the final product, wherein each 0.1ml contains 0.0225g of medicinal powder and 0.2ml/10 g.

Storage conditions of the test substance: storing at 4 deg.C in dark

2. Toxin counteracting toxic strain

Strain name: SARS-CoV-2

The infection route is as follows: nose drop

The infection dose: 10⁵TCID₅₀A

Infection volume: 50 microliter

3. Laboratory animal

Name of animal: hACE2 transgenic mice

Animal grade: SPF stage

Age of animal: 10-12 weeks old

Animal body weight: the weight is 20-24g

Animal sources: institute of animal research for medical experiments of Chinese academy of medical science

4. The experimental method comprises the following steps:

animal grouping: divided into dampness-resolving and toxin-vanquishing granule group and model group

Number of animals per group: 6 are

Administration dose: administered in a volume of 0.2ml/10g body weight (provided by the consignor)

The administration route is as follows: gavage stomach

The administration time is as follows: 1 hour after toxin challenge, 1 time per day, and 5 days after continuous administration, and normal saline was administered according to the same volume in the model group

5. Observation index

Continuously observing for 5 days after virus challenge, recording body weight change, detecting tissue virus energy by euthanasia of mice 5 days after infection, measuring lung weight, and calculating lung index, wherein 1 mouse conventionally takes left lung tissue for pathological examination

6. Data statistical processing method

Quantitative data generated in the experiment are subjected to variance analysis by using statistical processing software SPSSVersion 170.

(II) results of the experiment

1. Clinical manifestations of animals:

the model group mice showed weight loss after infection, with an average percentage of loss of up to 5.75%. Compared with the model group, the mice in the dampness-resolving and toxin-vanquishing granule group continuously lose weight after infection, and the weight loss percentage on the 5 th day is 13.33%. The weight reduction rate of the mice in the group given dampness-resolving and toxin-vanquishing particles after infection is obviously higher than that of the mice in the model group.

The average lung index of the mice in the model group is 1.16, compared with the mice in the model group, the average lung index of the mice in the dampness-resolving and toxin-vanquishing particle group is 1.14, and has no significant difference with the mice in the model group, see table 5, which shows that the lung index of the mice in the dampness-resolving and toxin-vanquishing particle group is not obviously improved after the mice are infected.

The lung tissue load of each group of test mice is significantly different from that of the model group when p is less than 0.05

Lung tissue weight/mouse body weight 100= lung index

2. Viral load capacity:

the hACE2 transgenic mouse model was infected with SARS-CoV-2 and the effect of inhibiting the virus in vivo was observed. The detection result of the lung tissue virus load 5 days after the infection of the model group mice is 10^5.58copies/ml. The lung tissue virus capacity of the mice in the dampness-resolving and toxin-vanquishing granular group is 10 after 5 days of infection^3.94copies/ml, significantly lower than model group. The granules for eliminating dampness and detoxifying have obvious virus inhibiting effect. See table 6:

3. Pathological diagnosis:

the mice in the hACE2 transgenic model group infected by SARS-CoV-2 for 5 days show diffuse moderate interstitial pneumonia change, and can be seen in alveolar septal broadening, inflammatory cell infiltration, small inflammatory cell infiltration around blood vessels, interstitial blood vessel dilatation congestion, small inflammatory cells in alveolar cavities and serous exudation.

The lung tissues of the mice in the dampness-resolving and toxin-vanquishing granule group are changed by mild interstitial pneumonia, and mild alveolar septal broadening, a small amount of inflammatory cell infiltration around blood vessels and interstitial vessel dilatation congestion can be seen; focal pulmonary edema, serous fluid in the alveolar space and a small amount of inflammatory cells exude.

The results show that compared with the model group, the pulmonary alveolar septal broadening of the dampness-resolving and toxin-removing particle group is reduced to a certain extent, but focal pulmonary edema appears, and the pulmonary tissue disease cases are not obviously improved, as shown in fig. 8 and 9 and table 7:

note: +, mild lesions; +, moderate lesions; + + + +, severe lesions; and a very severe lesion.

Grading standard of lung lesion:

widening of alveolar septum: mild lesions with mild broadening of alveolar septum. And the lung alveolar septum is obviously widened in moderate lesion, and the lesion range is larger than 1/4. And the lung and lung diseases are seriously affected, the alveolar septa are obviously widened, the alveolar septa are widened and fused, the alveolar spaces are obviously narrowed, and the lesion range is larger than 2/4. And the lung tissue is changed to be larger than 3/4 due to the fact that the lung alveolar septa are widened and fused, the alveolar spaces are obviously narrowed and disappear, and the local lung tissue is changed to be firm.

Other lesions (f exudation in the alveolar sacs, inflammatory cell infiltration, vasodilatation congestion, hemorrhage, etc.); +, mild lesions, less lesion than the cut lung tissue 1/4. And the pathological changes are about 1/4-2/4 in the lung tissue section. And the lesion range is about 2/4-3/4 of the section of lung tissue.

(III) experimental conclusion:

according to the virus replication, clinical manifestation and pathological examination in mice, the dampness-resolving and toxin-removing particles with the dosage of 0.2ml/10g/d have obvious virus inhibiting effect on SARS-CoV-2 infected hACE2 transgenic mice, so that the virus load in the lung tissues of the mice is reduced by 10^3.94copies. The dampness-resolving and toxin-vanquishing granules have no obvious effect of improving clinical symptoms and pulmonary inflammation.

Thirdly, for the treatment of 2019 patients with novel coronaviruses, the results are as follows:

28 days 1 month in 2020, a Chinese and western medicine combined ward is set up in the gold and silver pond hospital in Wuhan City, 43 beds are set up, the medical team of Chinese academy of traditional Chinese medicine is responsible for receiving and treating 121 cases of patients in a Chinese and western medicine combined treatment mode, 80 cases are discharged at present, wherein 32 cases of traditional Chinese medicine treatment are mainly dampness-resolving and toxin-vanquishing particles, and are supplemented with traditional Chinese medicines according to the state of an illness, and the treatment injection conditions are summarized as follows

(I) research method

1. Purpose of study

The efficacy and the safety of the dampness-resolving and toxin-vanquishing granules for treating the new coronary pneumonia are evaluated.

2. Research population

Hospitalized patients taking dampness-eliminating and toxin-removing granules between 28 days of 1 month and 28 days of 2020 to 4 days of 3 months of 2020.

3. Design of research

Non-random, prospective, observational studies.

4. Data source and acquisition method

The data source is as follows: obtaining information such as patient medical record records, laboratory examinations, medical advice lists, CT report lists and the like through an HIS system; the doctor of the front line observes and records the traditional Chinese medicine syndrome of the patient.

(II) selection and withdrawal of subjects

1. Diagnostic criteria:

the suspected case also has one of the following etiology, serology or chest imaging evidence:

(1) detecting the positivity of the novel coronavirus nucleic acid by real-time fluorescence RT-PCR;

(2) viral gene sequencing, highly homologous to known novel coronaviruses;

(3) serum positive for novel coronavirus specific IgM antibodies and IgG antibodies; the serum specific IgG antibody of the novel coronavirus is converted from negative to positive or the recovery phase is increased by 4 times or more than the acute phase.

(4) Early CT in the chest showed multiple small spots and changes in the interstitium, with obvious extrapulmonary zones. Further, the lung disease develops into a double lung multiple-wear glass shadow and a infiltrative shadow, and the severe cases can cause lung excess change, so that pleural effusion is rare.

2. Inclusion criteria were:

patients must meet all of the following inclusion criteria to be eligible for the study

(1) Age 18-80 years;

(2) meeting the diagnosis standard of the new coronary pneumonia;

(3) patients were able and willing to sign informed consent and comply with the study protocol.

3. Exclusion criteria

Patients meeting any of the following exclusion criteria were not enrolled in the study:

(1) severe primary diseases such as severe heart-lung, cerebrovascular, hematopoietic and endocrine systems are complicated;

(2) pregnant and lactating women;

(3) patients who are participating in other clinical trials;

(4) poor control of psychotic patients.

4. Exit criteria

(1) Regardless of the reason, the patient is unwilling or impossible to continue the clinical trial, placing a request to the attending physician to withdraw from the study and discontinue the researcher;

(2) subjects who did not specifically withdraw from the study, but who no longer received medication and testing and were therefore also "withdrawn" (or "dropped"). The reason for its exit should be understood and recorded as much as possible. Such as:

the patients feel intolerant to certain adverse reactions; failure to continue to receive clinical trials for other reasons; or missed visits for reasons not stated, etc.

5. Rejection criteria

(1) Major deviation of protocol. The subjects were found to be out of compliance with the inclusion criteria of the study protocol and continued participation in the study may pose an unacceptable risk to the health of the subjects.

(2) The disease condition worsens in the research process, and the clinical testers should be stopped according to the judgment of doctors;

(3) lack of effectiveness. The investigator determined that the subject did not benefit from the study treatment and continued participation in the study would pose an unacceptable risk to the subject;

(4) accidental pregnancy.

(III) study protocol

1. Research medicine

Name: dampness-resolving toxin-vanquishing prescription

The manufacturer: traditional Chinese medicine Yongzi company of national medicine group: guangdong Fang pharmaceuticals Co Ltd

The preparation formulation is as follows: compound granule

The taking method comprises the following steps: a set of two small boxes. One box for each patient in the morning and evening; the patients with serious illness follow the medical advice.

2. General treatment

(1) Bed rest, strengthen the support treatment, guarantee the abundant heat; the balance of water and electrolyte is noticed, and the internal environment is maintained to be stable; vital signs, finger oxygen saturation, etc. are closely monitored.

(2) Blood routine, urine routine, CRP, biochemical indices (liver enzyme, cardiac enzyme, kidney function, etc.), blood clotting function, arterial blood gas analysis, chest imaging, etc. are monitored according to the condition. Cytokine detection is feasible in the case of the conditions.

(3) Timely administration of effective oxygen therapy, including nasal catheter, mask oxygen delivery and nasal high flow oxygen therapy.

(4) Antiviral treatment: using alpha-interferon (500 ten thousand U per adult or equivalent dose, adding sterile water for injection 2mL, 2 times daily aerosol inhalation), lopinavir/ritonavir (adult 200mg/50 mg/granule, 2 granules each time, 2 times daily, treatment course no more than 10 days), ribavirin (recommended to be combined with interferon or lopinavir/ritonavir, 500 mg/adult, 2 to 3 times daily intravenous infusion, treatment course no more than 10 days), and abidotril (adult 200mg, 3 times daily, treatment course no more than 10 days).

(IV) statistical method

The statistical method comprises the following steps: continuous variables list mean and standard deviation or median and upper and lower quartiles, and carry out normality test and homogeneity of variance test, and under the condition of satisfying normal distribution and being uniform in variance, carrying out comparison among groups by adopting a t test, or else, carrying out comparison among groups by adopting a Wilcoxon rank sum test; the categorical variables are listed as frequency and percentage and compared using chi-square test or Fisher's exact probability method. And (3) carrying out front-to-back comparison in the group, wherein the continuous variable adopts a pair t test/symbol rank test, and the classification variable adopts an McNemar test or an McNemar-Bowker test. Survival analysis was performed using the log-rank test or Breslow test.

(V) analysis of results

1. Baseline analysis

32 patients 17 men and 15 women, mean age 55.34 years (55.34 ± 12.08), who were all born as good as cattle

The Chinese medicinal composition comprises 6 cases of cardiovascular and cerebrovascular diseases, 2 cases of respiratory system diseases, 4 cases of malignant tumors, 1 case of digestive system diseases and 3 cases of endocrine system diseases. The number of days of hospitalization (11.56 +/-4.70) days, the time for transferring the nucleic acid to the negative (10.41 +/-5.75) days after diagnosis, the time for transferring the nucleic acid to the negative (5.82 +/-5.24) days after hospitalization, the time for transferring the nucleic acid to the negative (5.09 +/-5.13) days after traditional Chinese medicine treatment and the clinical remission time (8.16 +/-4.55) days.

Table 8 patient baseline

2. Analysis of efficacy

(1) Comparison of basic vital signs before and after treatment

After treatment, the body temperature is obviously reduced (from 36.96 +/-0.73 to 36.65 +/-0.20) (P is less than 0.05),

the systolic pressure (129.9 +/-14.57 is reduced to 122.61 +/-14.36) and the diastolic pressure (82.74 +/-10.41 is reduced to 74.35 +/-9.69) are all obviously reduced after treatment (P is less than 0.05). The statistics of the patient before and after the treatment of the respiration and the heart rate have no obvious difference.

TABLE 9 comparison of basic vital signs before and after treatment

(2) Comparison of laboratory indices before and after treatment

2.1 routine of blood

The percentage of lymphocytes is not changed before and after the treatment, but the absolute value of the lymphocytes is obviously increased (1.32 +/-0.47-1.55 +/-0.5) after the treatment (P is less than 0.05); there was a significant decrease (2.92 ± 1.42 to 2.34 ± 0.66) in absolute neutrophil/absolute lymphocyte (P < 0.05) after treatment; the absolute value and percentage of eosinophil are increased (P is less than 0.001); there was a decrease (128.38 ± 12.91 to 123.72 ± 11.1) (P < 0.05) after treatment with hemoglobin concentration, but the mean was in the normal range; a significant increase (226.84 + -72.45 to 262.41 + -87.79) (P < 0.05) following platelet treatment; there were no statistical differences between neutrophil counts and percentage before and after treatment (P > 0.05).

2.2 inflammatory factors

C-reactive protein is reduced from (28.12 +/-38.46) to (4.88 +/-8.77), and compared before and after treatment, the statistical difference is generated (P < 0.001); the ferritin treatment is obviously reduced (523.55 + -404.61-323.18 + -196.23) (P < 0.001); there was a significant decrease (102.29 + -112.73 to 51.53 + -106.32) (P < 0.001) following treatment with amyloid A; there was a significant drop (43.8 ± 23.32 to 37.59 ± 24.9) after treatment of blood sedimentation (P < 0.05). Other indexes such as procalcitonin and IL-6 have no obvious change.

2.3 myocardial enzymes

A significant decrease (from 107.78 ± 98.92 to 54.53 ± 17.08) after creatine kinase treatment (P < 0.001); a significant decrease (from 53.65 + -47.29 to 34.38 + -14.05) (P < 0.05) after myoglobin treatment; a significant decrease (from 199.91 + -76.62 to 148.47 + -38.57) after treatment with alpha-hydroxybutyrate dehydrogenase (P < 0.001); a significant decrease (from 256.53 + -84.67 to 212.84 + -43.4) (P < 0.05) after lactate dehydrogenase treatment; a significant decrease (from 4.55 ± 3.92 to 3.78 ± 3.45) after troponin treatment (P < 0.05); the rest cardiac indexes such as creatine kinase isoenzyme and BNP have no obvious change.

2.4 hepatic and renal function

The blood albumin treatment has obvious increase (34.12 plus or minus 3.36 to 36.91 plus or minus 4.18) (P < 0.001), and the total protein has obvious increase (65.12 plus or minus 5.74 to 68.44 plus or minus 4.84) (P < 0.05); there was a significant decline (74.02 + -25.11 to 69.58 + -22.14) (P < 0.05) following creatinine treatment; the treatment of glutamic-oxaloacetic transaminase is obviously reduced (33.03 + -16.91 to 23.34 + -8.02) (P is less than 0.05); there was a significant decrease (40.38 + -26.46 to 35.84 + -26.98) after r-glutamyl transpeptidase treatment (P < 0.05). The glutamic-pyruvic transaminase and urea have no obvious change.

2.5 blood oxygen saturation and blood coagulation index

The blood oxygen saturation and D dimer have no obvious change (P > 0.05).

TABLE 10 comparison of laboratory indices before and after treatment

(3) Comparison of clinical symptom-outcome to baseline

The clinical symptoms of fever, cough, hypodynamia and dry mouth are obviously relieved after the treatment (P is less than 0.05), and the other symptoms are not obviously changed before and after the treatment.

TABLE 11 comparison of laboratory indices before and after treatment

(VI) conclusion

The results show that 32 cases of COVID-19 hospitalized patients are treated by the dampness-resolving and toxin-vanquishing particles, and the effects are very obvious no matter the clinical symptoms or the physicochemical examination including the negative conversion time of nucleic acid detection. The mean time to negative conversion of nucleic acid was 5.09 days, the mean time to clinical remission was 8.16 days, and the mean number of hospitalization days was 11.56 days. Has remarkable effects of improving symptoms of fever, cough, hypodynamia and dry mouth. From physical and chemical examination, the inflammatory indexes of blood sedimentation, C-reactive protein, ferritin and amyloid A are obviously reduced, and the inflammatory indexes of lymphocyte are obviously increased after absolute value treatment; the indexes of the function of the reactor body such as albumin are obviously improved after treatment, five indexes of myocardial enzyme and the functions of liver and kidney are well recovered. The dampness-resolving and toxin-vanquishing particles are proved to have good effects of resisting viruses and inhibiting inflammatory states, have good safety, recover the physiological functions of human bodies and accord with the treatment concept of strengthening body resistance and eliminating pathogenic factors in traditional Chinese medicine. The typical case more intuitively reflects the good curative effect of the dampness-resolving and toxin-vanquishing particles and plays an important role in the treatment of resisting COVID-19.

While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.

Claims

1. A preparation method of a traditional Chinese medicine composition for eliminating dampness and removing toxin is characterized by comprising the following steps:

(2) decocting 7.5-150 parts of gypsum in water;

(5) decocting the residue with water, and filtering to obtain second decoction;

(8) determining the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxicity, wherein the effective components comprise one or more of the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, the content of combined anthraquinone and the content of paeoniflorin.

2. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity as claimed in claim 1, wherein in step (2), the raw gypsum is decocted for 20-40 minutes, and the amount of water added is 1-6 times of the twelve medicines of ephedra herb, fried bitter apricot seed, raw gypsum, liquorice, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red peony root.

3. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity according to claim 1, wherein in the step (3), the decoction is carried out in water for 40-60 minutes, and the amount of the water added is 2-7 times of that of the twelve medicines, namely ephedra herb, fried bitter apricot seed, gypsum, liquorice, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, astragalus mongholicus, semen lepidii and red peony root.

4. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity according to claim 1, wherein in the step (4), the pogostemon cablin and the rhubarb are added, and the decoction is carried out for 5-15 minutes, wherein the adding amount of water is 6-10 times of that of the pogostemon cablin and the rhubarb.

5. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity as claimed in claim 4, wherein in the step (4), the herba Pogostemonis and the radix Et rhizoma Rhei are added, and the decoction time is 8-12 minutes, and the water addition amount is 8 times of that of the herba Pogostemonis and the radix Et rhizoma Rhei.

6. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity according to claim 1, wherein in the step (5), the decoction dregs are further decocted with water for 40-80 min, and the added water amount is 6-10 times of that of the fourteen medicaments of ephedra herb, fried bitter apricot seed, gypsum, liquorice, patchouli, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rhubarb, astragalus mongholicus, pepperweed seed and red peony root.

7. The method for preparing the dampness-resolving and toxin-vanquishing traditional Chinese medicine composition as claimed in claim 6, wherein in the step (5), the herb residue is decocted with water for 50-60 min, and the amount of the added water is 8 times of that of the fourteen medicines of ephedra herb, fried bitter apricot seed, gypsum, liquorice, patchouli, magnolia officinalis, bran-fried rhizoma atractylodis, fried grass nut, rhizoma pinellinae praeparata, poria cocos, rheum officinale, astragalus membranaceus, pepperweed seed and red peony root.

8. The method for preparing a Chinese medicinal composition for eliminating dampness and removing toxicity of claim 1, wherein the step (6) comprises:

9. The method of claim 1, wherein the total content of ephedrine hydrochloride and pseudoephedrine hydrochloride, the total anthraquinone content, the free anthraquinone content and the paeoniflorin content in the dampness eliminating and toxin removing composition are determined by high performance liquid chromatography, and the bound anthraquinone content is calculated, wherein the bound anthraquinone content = the total anthraquinone content-the free anthraquinone content.

10. The method for preparing the traditional Chinese medicine composition for eliminating dampness and removing toxicity of claim 9, wherein the total content of the ephedrine hydrochloride and the pseudoephedrine hydrochloride is 0.7-2.7 mg/g;

the content of the paeoniflorin is 3-10 mg/g;

the bound anthraquinone content should not be less than 0.016%.

11. A preparation method of a traditional Chinese medicine composition for eliminating dampness and removing toxin is characterized by comprising the following steps:

(4) decocting the residue with water, and filtering to obtain second decoction;

(7) determining the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxicity, wherein the effective components comprise one or more of the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, the content of combined anthraquinone and the content of paeoniflorin.

12. The method of claim 11, wherein the total content of ephedrine hydrochloride and pseudoephedrine hydrochloride, the total anthraquinone content, the free anthraquinone content and the paeoniflorin content in the dampness eliminating and toxin removing composition are determined by high performance liquid chromatography, and the bound anthraquinone content is calculated, wherein the bound anthraquinone content = the total anthraquinone content-the free anthraquinone content.

13. A preparation method of a traditional Chinese medicine composition for eliminating dampness and removing toxin is characterized by comprising the following steps:

(3) decocting the residue with water, and filtering to obtain second decoction;

(6) determining the effective components of the traditional Chinese medicine composition for eliminating dampness and removing toxicity, wherein the effective components comprise one or more of the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride, the content of combined anthraquinone and the content of paeoniflorin.

14. The method of claim 13, wherein the total content of ephedrine hydrochloride and pseudoephedrine hydrochloride, the total anthraquinone content, the free anthraquinone content and the paeoniflorin content in the dampness eliminating and toxin removing composition are determined by high performance liquid chromatography, and the bound anthraquinone content is calculated, wherein the bound anthraquinone content = the total anthraquinone content-the free anthraquinone content.

15. The application of the traditional Chinese medicine composition for eliminating dampness and detoxifying prepared by the preparation method of any one of claims 1-14 in antiviral drugs.

16. The use of claim 15, wherein the antiviral agent is a medicament for the treatment of a coronavirus.

17. The use of claim 16, wherein the antiviral agent is a novel coronavirus agent for the treatment 2019.